СПОСОБ ОПРЕДЕЛЕНИЯ ВИТАМИНА B12 В ВОДНЫХ РАСТВОРАХ

Изобретение относится к аналитической химии, в частности к химии органических соединений, и может быть использовано при разработке процессов выделения и определения витаминов. Способ характеризуется тем, что готовят водно-солевой раствор витамина B12, который "имеет рН 5,3±0,3, для чего раствор витамина B12 фармакопейной чистоты помещают в мерную колбу, доводят до метки насыщенным раствором сульфата аммония, затем экстрагируют витамин B12 изопропиловым спиртом квалификации х.ч., для этого к полученному раствору витамина В12 добавляют изопропидовый спирт при соотношении объемов водно-солевого раствора витамина B12 и органической фазы 20:1, экстрагируют в течение 4-5 мин до установления межфазного равновесия, после расслаивания системы водную фазу отделяют от органической и анализируют методом УФ-спектрофотометрии, строят градуировочный график зависимости оптической плотности водно-солевого раствора от концентрации витамина B12, на УФ-спектрофотометре в кварцевой кювете l=1 см при длине волны ...

БОРСОДЕРЖАЩЕЕ СОЕДИНЕНИЕ

Изобретение относится к новому борсодержащему соединению, а именно к соединению, соответствующему следующей формуле 1, или его фармацевтически приемлемой соли, выбранной из соли щелочного металла, соли аммония, соли тетраалкиламмония (NR4+) или соли тетрафенилфосфония:[Формула 1]В формуле 1: черный круг обозначает атом B, белый круг обозначает B-H; -R1обозначает -(CH2)n-X1-R3(n обозначает целое число от 0 до 6; X1обозначает O-CO, или отсутствует; R3обозначает C6-C20алкил, гидрокси C6-C20алкил, амино C6-C20алкил, азидо C6-C20алкил, гидроксикарбонил C6-C20алкил, замещенный, где заместители представляют собой нитро, гидроксил, B(OH)2, или незамещенный фенокси C6-C20алкил, замещенный, где заместитель представляет собой диоксифенилксантен, или незамещенный фенилтиомочевина C6-C20алкил, или незамещенную бензильную группу), или группу, имеющую повторяющуюся последовательность -(CH2)2-O- 3 раза или более и 10 раз или менее и имеющую метильную группу или этильную группу на конце со стороны атома ...

МЕТАЛЛОЦЕНОВЫЕ ПРОИЗВОДНЫЕ САХАРОВ И СОДЕРЖАЩЕЕ ИХ СРЕДСТВО ДЛЯ АКТИВАЦИИ КИЛЛИНГА МИКРООРГАНИЗМОВ,ЛОКАЛИЗОВАННЫХ ВНУТРИКЛЕТОЧНО

Изобретение относится к производным сахаров общей формулы (1), где n= 1-6, остаток (2) - сахаридный радикал, содержащий в качестве концевого невосстанавливающего сахара, связанного в положении С-1 углерод, маннозу или фукозу, или N-ацетилглюкозамин; Y - мостиковая группа, представляющая собой алифатический углеводород с числом углеродных атомов в цепи от 1 до 6, ковалентно связанный с сахаридным радикалом в положении С-1 углерод посредством простой эфирной связи или через группу -С(O)- и связанный с металлоценом посредством сложноэфирной связи или через группу -NH-C(O)-; СрМе - металлоцен. Соединения по изобретению обладают противоинфекционной активностью. Также предложено средство для активации киллинга микроорганизмов, локализованных внутриклеточно, содержащее в качестве активного ингредиента соединение формулы (1). 2 с. и 2 з.п.ф-лы, 2 ил., 1 табл.

АСИММЕТРИЧНАЯ ВСПОМОГАТЕЛЬНАЯ ГРУППА

Изобретение относится к хиральному реагенту формулы (I') для получения производного нуклеозид 3'-фосфорамидита формул (Va') или (Vb'), которые могут использоваться в химической промышленности для синтеза олигонуклеотидов:где Gпредставляет собой H или группу формулы (II), Gпредставляет собой группу формул (III) или (V), или Gи Gвместе образуют группу формулы (IV),,,,,где G- Gпредставляют собой H или нитрогруппу, G- Gпредставляют собой Салкил или Сарил, G- Gпредставляют собой Н, G- Gпредставляют собой H или Салкил. Предложены новые реагенты и полученные с их использованием новые производные нуклеозид 3'-фосфорамидита формул (Va') или (Vb'), эффективные для синтеза олигонуклеотидов,,,где Gпредставляет собой 4,4'-диметокситритил, Rпредставляет собой Н, О-Салкил, галоген, Rпредставляет собой -СН-, и Bs выбран из остатков немодифицированных и модифицированных нуклеозидов. Предложены новые эффективные способы синтеза указанных производных олигонуклеотидов. 6 н. и 8 з.п. ф-лы, 69 пр., 1 табл., ...

СПОСОБ СИЛИЛИРОВАНИЯ УГЛЕВОДОВ

Описывают способ силилирования углеродов в жидком NH3, причем углеводы превращают под давлением в автоклаве при температуре около 0 до 200oC c cилилирующим средством формулы (I) (I) в жидком азотном соединении формулы (II) (II) причем в обеих формулах (I) и (II) соответствующие остатки, независимо друг от друга, представляют: R1R2R3R10= H; R4R5R6R7R8R9= CH3. Особенно выгодным силилирующим средством является гексаметилдисилазан. В качестве жидкого азотистого соединения используют преимущественно аммиак, который является жидким в условиях способа. Способ изобретения имеет преимущества как с точки зрения экологии, так и с точки зрения экономики. Полученные по изобретению продукты способа являются особенно чистыми, что делает возможным их дальнейшие выгодные переработки. 1 табл.

СПОСОБ ПОЛУЧЕНИЯ КООРДИНАЦИОННЫХ СОЕДИНЕНИЙ ОЛИГОГАЛАКТУРОНОВОЙ КИСЛОТЫ С БИОГЕННЫМИ МЕТАЛЛАМИ (II), КАК СИСТЕМ ДОСТАВКИ БИОГЕННЫХ МЕТАЛЛОВ (II) И СИСТЕМ ВЫВЕДЕНИЯ ТЯЖЕЛЫХ МЕТАЛЛОВ (II)

Изобретение относится к медицине, а именно к фармакологии, и описывает способ получения координационных соединений олигогалактуроновой кислоты с биогенными металлами (II). Способ включает получение из пектинсодержащего препарата олигогалактуроновой кислоты со степенью полимеризации не менее 10, подвергаемой взаимодействию с солью металла (II): меди, кобальта, железа, цинка, марганца, магния в водной среде при нейтральной pH, экспозицию реакционной смеси при комнатной температуре, нейтрализацию образовавшейся кислоты, водную промывку, центрифугирование и высушивание осадка. Согласно изобретению к 1 л 5,0·10M водного раствора очищенной олигогалактуроновой кислоты при перемешивании добавляют сначала 2 M водный раствор гидрата аммиака до pH 8, затем 1 л 4,5·10M водного раствора ацетата металла (II); образующийся гелеобразный осадок обрабатывают 96% этанолом при объемном соотношении 1:2, выдерживают 2 ч. Изобретение обеспечивает доставку биогенных металлов (II), а также выведение катионов тяжелых ...

ПРОИЗВОДНЫЕ КОБАЛАМИНА, ПРЕДНАЗНАЧЕННЫЕ ДЛЯ ДИАГНОСТИКИ И ЛЕЧЕНИЯ АНОМАЛЬНОЙ ПРОЛИФЕРАЦИИ КЛЕТОК

... 1. Производное кобаламина (а) не обладающее связывающей аффинностью или обладающее низкой связывающей аффинностью в отношении транскобаламина II и (б) сохраняющее активность заменителя витамина В12. 2. Производное кобаламина по п.1, (а) обладающее менее 20% связывающей аффинности в отношении транскобаламина II по сравнению со связывающей активностью немодифицированного кобаламина, которую определяют методом анализа связывания, и (б) сохраняющее более 2% активности заменителя витамина В12, которую определяют методом анализа с использованием роста клеток. 3. Производное кобаламина по п.1, (а) обладающее менее 10% связывающей аффинности в отношении транскобаламина II по сравнению со связывающей активностью немодифицированного кобаламина, которую определяют методом анализа связывания, и (б) сохраняющее более 10% активности заменителя витамина В12, которую определяют методом анализа с использованием роста клеток. 4. Производное кобаламина по п.1, (а) обладающее менее 5% связывающей аффинности ...

БОРСОДЕРЖАЩЕЕ СОЕДИНЕНИЕ

КАЛИЕВЫЕ СОЛИ РАЗНОЛИГАНДНЫХ КООРДИНАЦИОННЫХ СОЕДИНЕНИЙ МАГНИЯ С ГИСТИДИНОМ АДЕНОЗИН-5'-ТРИФОСФАТОМ И КРЕАТИНФОСФАТОМ, ПРОЯВЛЯЮЩИЕ ЗАЩИТНОЕ ДЕЙСТВИЕ НА МИОКАРД ОТ ИШЕМИЧЕСКОГО ПОВРЕЖДЕНИЯ

Калиевые соли разнолигандных координационных соединений магния с гистидином, аденозин-5'-трифосфатом и креатинфосфатом общей формулы KnMg(His)(MP)mH2O, где His - анион гистидина (His-), МР - анион макроэргического фосфата (аденозин-5'-трифосфата АТР4- или креатинфосфата CRP2-), n=1 или 3, m=7 или 8, проявляющие защитное действие на миокард от ишемического повреждения.

СПОСОБ ОПРЕДЕЛЕНИЯ ВИТАМИНА В12 В ВОДНЫХ РАСТВОРАХ

Способ определения витамина В12 в водных растворах, характеризующийся тем, что готовят водно-солевой раствор витамина B12, который имеет рН 5,3±0,3, для чего раствор витамина B12 фармакопейной чистоты помещают в мерную колбу, доводят до метки насыщенным раствором сульфата аммония, затем экстрагируют витамин В12 изопропиловым спиртом квалификации х.ч., для этого к полученному раствору витамина B12 добавляют изопропиловый спирт при соотношении объемов водно-солевого раствора витамина B12 и органической фазы 20:1, экстрагируют в течение 4-5 мин до установления межфазного равновесия, после расслаивания системы водную фазу отделяют от органической и анализируют методом УФ-спектрофотометрии, строят градуировочный график зависимости оптической плотности водно-солевого раствора от концентрации витамина B12, на УФ-спектрофотометре в кварцевой кювете l=1 см при длине волны 361 нм измеряют оптическую плотность водно-солевого раствора, по градуировочному графику определяют концентрацию витамина B12 ...

КОМПЛЕКСНЫЕ СОЕДИНЕНИЯ ЖЕЛЕЗА ДЛЯ ТЕРАПЕВТИЧЕСКОГО ПРИМЕНЕНИЯ

Настоящее изобретение относится к способу получения комплексных соединений железа. Предложенный способ включает стадии: (i) предоставления препарата железа, содержащего железо, в форме, выбранной из растворимой в воде соли железа, гидроксида железа или оксида-гидроксида железа, где количество мышьяка в препарате железа не превышает 4,5 мкг на г железа и количество свинца в препарате железа не превышает 1,5 мкг на г железа; и (ii) приведения в контакт препарата железа с углеводным лигандом в присутствии воды с получением комплексного соединения железо-углевод. Технический результат заключается в предоставлении способа получения продуктов железа, которые являются безопасными для введения человеку и сельскохозяйственным животным, а также для людей, употребляющих пищу, являющуюся продуктом животноводства. 10 з.п. ф-лы, 1 табл., 4 пр.

Способ получения с-силилированных производных углеводов

PLATIN-VERBINDUNGEN, GEEIGNET ZUR VERWENDUNG ALS ARZNEIMITTEL.

Immunobestimmung mit Nichtmetallmarkierungen.

Glycosidic iron(II) and iron(III) complex compositions and their use

The invention relates to glycosidic iron(II) and iron(III) complex compositions prepared by reacting iron(II) hydroxide and/or iron(III) hydroxide with reducing or non-reducing sugars in the presence of alkalis, for use as pharmaceuticals, where appropriate in conjunction with conventional vehicles and additives, and to the use of these iron complex compositions for the production of a pharmaceutical for anaemic states and as feed additive in piglet rearing.

Verfahren zur Gewinnung von Vitamin B

Markierte Nukleinsäuren.

5-SUBSTITUIERTE URIDINDERIVATE UND ZWISCHENPRODUKTE.

Therapeutische Anwendungen von 2',5'-Oligoadenylat-Derivaten

PLATINENTHALTENDE VERBINDUNG, VERFAHREN ZU DEREN HERSTELLUNG SOWIE DEREN VERWENDUNG

KÜNSTLICHE REZEPTOR-ANALOGE.

Verfahren zur Gewinnung von Konzentraten der Vitamine der B-Gruppe aus Faulschlamm

Verfahren zur Herstellung von nukleotidhaltigen Hydroxo (Aquo)-cobalaminen

Perfluoralkylhaltige Komplexe mit Zuckerresten, Verfahren zu deren Herstellung und ihre Verwendung

Perfluoralkylhaltige Komplexe mit Zuckerresten der allgemeinen Formel I DOLLAR F1 in der R einen über die 1-OH- oder 1-SH-Position gebundenen Mono- oder Oligosaccharidrest darstellt, R¶f¶ eine perfluorierte Kohlenstoffkette bedeutet, K ein Metallkomplex ist und Y und Z Linkergruppen darstellen, DOLLAR A sind für die intravenöse Lymphographie, für die Tumor-Diagnostik und für das Infarkt- und Nekrose-Imaging geeignet.

FESTPHASEN-SYNTHESE

Improvements in or relating to product having high vitamin b activity and process ofpreparing the same

A concentrate containing an animal growth factor having Vitamin B1 2 activity is obtained by extracting a sludge resulting from the microbiological treatment of sewage with a solvent for said factor and concentrating the resulting extract. The sludge employed is of the type known as activated sludge. The extract may be further treated, as by evaporation, absorption in charcoal and fractional extraction.ALSO:An animal feed comprises a product having high vitamin B12 activity which comprises a water-soluble fraction of a sludge resulting from the microbiological treatment of sewage incorporated in soybean meal, alfalfa leaf meal, linseed meal, cottonseed meal and various grain meals. Preferably the vegetable base of the feed is fortified with appropriate minerals and vitamins.

A process for stabilizing a vitamin b analogue

Aqueous solutions of Vitamin B12 compounds, especially solutions also containing Vitamin B1 compounds, are stabilized by adding maleic acid or a water-soluble sodium, potassium, calcium, magnesium, ammonium or triethanolamine maleate. Up to 2% by weight of the solution, e.g. 0.2 to 1% of the maleic acid or maleate may be used. In examples, solutions containing hydroxocobalamine and thiamine hydrochloride, thiamine tetrahydrofurfuryl disulphide hydrochloride and thiamine propyl disulphide, are stabilized with monosodium maleate and maleic acid; the solutions also contain nicotinic acid amide, benzyl alcohol, polyoxyethylene sorbitan and pyridoxine.ALSO:Aqueous solutions containing vitamin B12 compounds and vitamin B1 compounds, are stabilized by adding maleic acid or a water soluble sodium, potassium, calcium, magnesium, ammonium or triethanolamine maleate. Up to 2% by weight of the solution, e.g. 0.2 to 1%, of the maleic acid or maleate may be used. In Examples monosodium maleate and maleic ...

VITAMIN B12 DERIVATIVES HAVING PROLONGED ACTIVITY

... 1445495 Vitamin B 12 derivatives DR L ZAMBELETTI SpA 19 March 1974 [4 April 1973] 12209/74 Heading C2V A derivative of vitamin B 12 is obtained by a reaction in which the amido group of cobalamin is covalently linked to the hydroxyl groups of dextran. The derivative may contain 1À0 to 95% by weight of cobamide residues. It may be obtained by reacting dextran with cyanogen bromide and reacting the product with cobamide. The derivative has vitamin B 12 activity of prolonged duration. Examples are given.

Compounds for mass spectrometry

Recovery of vitamin b

Vitamin B12 is obtained by growing a mycelium bearing organism of the Streptomyces species or other mycelium bearing organisms known to produce vitamin B12 in a culture medium adapted to the production of vitamin B12, concluding the fermentation before substantially any autolysis of the cell structure takes place, separating the mycelium from the culture broth obtained, extracting said mycelium with hot water at a pH of 6-9 and recovering the vitamin B12 from the aqueous extract obtained. The mycelium is separated from the culture broth by centrifugation or filtration and extracted with hot water. The aqueous extract may be treated with a proteolytic enzyme to digest the proteinaceous matter present and extracted with a water immiscible organic solvent, e.g. butyl alcohol, isobutyl alcohol and amyl alcohol and the solvent extract concentrated by evaporation.

3-deoxy-ribofuranosyl derivatives

Compounds of the formula where X is halogen and R is an acyl radical may be obtained by reacting a compound of the formula wherein R11 is an alkyl group, with a halogenating system capable of producing a halogen anion in the presence of a strong acid under anhydrous conditions, suitably in the presence of an inert organic solvent. The halogenating agent may be a hydrogen or thionyl halide (both of which may also function as the strong acid) or a metal halide.

Process for the separation of corrinoids

The invention relates to the separation of corrinoids, more particularly to the separation of corrinoids by selective adsorption and/or selective elution on a polymeric absorbent having a large specific surface. The process according to the invention is equally suitable for the separation of incomplete corrinoids from complete corrinoids and various complete corrinoids, preferably vitamin B12 and factor III from each other.

A solution of metal-polymer chelate(s) and applications thereof(cleaner)

Cis-diammineplatinum(II) organophosphate complexes

Cis-diammineplatinum(II) organophosphate complexes where the organophosphate moiety is a glycerophosphate or a monosaccharide phosphate moiety are prepared by reaction of cis-diaquodiammineplatinum(II) salts with alkali metal organophosphates. The resulting complexes possess pronounced anti-tumor activity in mice and low toxicity; consequently, they have high therapeutic indices.

Polyether antibiotic zinc complexes

Zinc complexes of various monovalent and divalent polyether antibiotics are provided which act as coccidiostats and growth promoting agents when administered to food- producing animals such as cattle, sheep, swine and poultry. Soluble zinc salt is added to a fermentation beer containing the polyether antibiotics to form an insoluble, recoverable biomass containing the desired zinc antibiotic complex. The subject zinc complexes of polyether antibiotics may be administered in feed compositions and feed additive compositions, or as implants. The polyether antibiotics which may be used to make the subject zinc complexes include: linear monovalent and divalent polyethers (e.g. monensin, nigericin, lasalocid, lysocellin); non-glycolic monovalent monoglycoside polyethers (septamycin, dianemycin, lenoremycin, carriomycin and antibiotic A-204); mononitrogen- containing divalent pyrrole ethers (e.g. calcimycin, X- 14547); polynitrogen-containing divalent pyrrole ethers (e.g. A- 23187); glycolic monovalent ...

Improvements relating to organic aluminium compounds

Aluminas, suitable for catalysts and adsorbents, are prepared by calcining in an air oven at 550 DEG C. for 2 hours, Al3O2(OH)4 7/8 (sucrose) 1/8 , Al3O2(OH)4 31/32 (sucrose) 1/32 and Al3O2(OH)5. The aluminas so prepared have specified surface areas of 466 m.2/gm., 447 m.2/gm. and 462 m.2/gm. and micro-pore volumes of 0.92 ml./gm., 0.85 ml./gm. and 0.87 ml./gm. respectively when these are determined by low temperature gas adsorption at 77.4 DEG K. using nitrogen as adsorbate.ALSO:The invention comprises an organic aluminium compound of the formula Al3O2(OH)x(carbohydrate)y where x+y=5 and y is not more than 1, including compositions comprising a compound as defined together with up to 5% by weight of the alcohol corresponding to the alcoholate, and the preparation thereof by reacting together, while heating under reflux, aluminium alcoholates, water and carbohydrate materials, the amount of water being not more than 2+x moles per 3 moles of aluminium alcoholate. The water and carbohydrate ...

Synthesis of daunosamine hydrochloride and intermediates used in its preparation

A process for synthesizing daunosamine hydrochloride is disclosed. Intermediates useful for synthesizing daunosamine hydrochloride, and processes for preparing such intermediates, are also disclosed.

The production of a selectively protected N-acylated derivative of an aminoglycosidic antibiotic

Aminoglycosidic antibiotic comprising a 6-0-(3''-aminoglycosyl)-2-deoxystreptamine optionally having a 4-0-(aminogycosyl) group, such as kanamycins, gentamicins, sisomicin, forms reversible complex with zinc cations by association of the zinc cations with some pairs of aminohydroxyl groups in the aminoglycoside, and the zinc-complexed amino groups are blocked from acylation. Reaction of this zinc complex with an acylation reagent having an amino-blocking acyl group brings about acylation of the non-complexed amino groups to give an N-acylated zinc complex, namely a complex of zinc cation with an N-acylated aminoglycosidic antibiotic derivative. Removal of zinc cations from N-acylated zinc complex yields a partially N-acylated aminoglycosidic antibiotic where 1- and 3''-amino groups are unprotected but all other amino groups protected with acyl group. Further reaction of this partially N-acylated product with a certain alkanoic acid or N-formyl-imidazole results in preferential acylation ...

Improvements in or relating to industrial production of hydroxocobalamine

In a process for the production of hydroxocobalamine wherein an aqueous acidic solution of cyanocobalamine is hydrogenated by contacting it with granulated zinc and then oxidized by bubbling in air or other oxygen-containing gas, there is added to the initial solution of cyanocobalamine a water-miscible organic solvent. The solvent, which may be used in an amount of 10% by volume of the cyanocobalamine solution, may be acetone, tetrahydrofurane, dioxane, methyl alcohol or ethyl alcohol. Examples are given.

CONVERSION OF CORRINOIDS

PROCESS FOR THE PREPARATION OF KANAMYCIN DERIVATIVES

... 1-N-[ omega -amino- alpha -hydroxyalkanoyl] kanamycins A and B of the formula I in which R represents OH or NH2, are prepared by acylation of polysilylated kanamycin A or B, or polysilylated kanamycin A or B which has a protective group other than silyl on the 6'-amino group, with an acylating derivative of an acid of the formula II in which n is an integer from 0 to 2 and B is an amino protective group, in an essentially anhydrous organic solvent and by subsequent removal of all blocking groups. The compounds have therapeutic properties.

METHOD FOR PREPARING AURANOFIN

Improvements in or relating to a process for the microbiological production of vitamin b

Vitamin B12 is obtained in a microbiological process by means of micro-organisms of the genus Streptomyces which is characterized in that to a culture medium thereof, at a time when the percentage of available quantity of nutrient substance in the culture liquid lies between 0.01 and 0.5 per cent by weight, is added further quantities of nutrient substance such that the percentage of available nutrient in the culture liquid is maintained between 0.01 and 0.5 per cent by weight, Vitamin B12 is recovered from the cell material thus produced. Preferably a quantity of nutrient substance is added such that the concentration thereof is kept at a value lying between 0.01 per cent and 0.05 per cent by weight. As nutrient substance there may be used glucose, maltose, lactose, saccharose, sorbitol and a protein hydrolysate.

PROCESS FOR PREPARING GOLD COMPOUNDS

Industrial manufactoring process of the hydroxocobalamine.

Process for the industrial production of the hydroxocobalamine.

Manufactoring process of the méthylcobalamine.

Industrial manufactoring process of the hydroxocobalamine.

Manufactoring process of the méthylcobalamine starting from the cyanocobalamine.

Agents of carbonation and their preparation.

Process of purification of the hydroxocobalamine

FUNGICIDES HETERO-CYCLIC AROMATIC AMIDES AND THEIR COMPOSITIONS, PROCEDURES FOR THEIR APPLICATION AND PRODUCTION

Diosmin derivative and process for its preparation

PROCEDURE FOR THE PRODUCTION OF NEW MURAMYLPEPTID ANTIGEN KONJUGATE ONES

PROCEDURE FOR MANUFACTURING AURANOFIN

PROCEDURE FOR THE PRODUCTION OF AURANOFIN

PROCEDURE FOR THE PRODUCTION OF IRON SACCHAROSE COMPLEX

PROCEDURE FOR THE PRODUCTION AGAIN HAEMINARGINAT AND/OR HAEMINLYSINAT

VERFAHREN ZUR O-, S- ODER NH-DIALKYLBORYLIERUNG

VERFAHREN ZUR HERSTELLUNG EINES SELEKTIV GESCHUETZTEN N-ACYLIERTEN DERIVATES EINES AMINOGLYCOSID-ANTIBIOTIKUMS

VERFAHREN ZUR HERSTELLUNG VON METHYLCOBALAMIN

PHOTOSENSIBILATOREN, THE GALECTIN RECOGNIZING, FOR PHOTO-DYNAMIC THERAPY

VERFAHREN ZUM HERSTELLEN VON AURANOFIN

VERFAHREN ZUR HERSTELLUNG VON AURANOFIN

VERFAHREN ZUR HERSTELLUNG VON NEUEN ORGANISCHEN EISENVERBINDUNGEN

3 ' - ETHYNYLCYTIDINDERIVAT

PROCEDURE FOR THE PRODUCTION SELECTIVELY OF A PROTECTING N-ACYLIERTEN OF DERIVATIVE OF AN AMINOGLYCOSID ANTIBIOTIC

PROCEDURE FOR MANUFACTURING AURANOFIN

PROCEDURE FOR THE PRODUCTION OF A NEW COMPLEX OF AN POLYAETHER ANTIBIOTIC

SACCHARIDE-CONTAINING FUNCTIONAL ONES ORGANOPOLYSILOXANE AND PROCEDURES FOR THEIR PRODUCTION

PROCESS FOR PREPARING NEW HYDROPHILIC SILANE AND SILOXANE DERIVATIVES AND PRODUCTS PREPARED BY THIS PROCESS

The invention describes hydrophilic silanes and, respectively, linear and crosslinked polysiloxanes, prepared by hydrosilylation of unsaturated carbohydrate derivatives with H-Si-functional silanes and, respectively, with polysiloxanes.

GLYCOSIDE REMAINDERS EXHIBITING ORGANOSILICIUMVERBINDUNGEN AND PROCEEDING TO THEIR PRODUCTION

OLIGORIBONUKLEOSIDE AND OLIGODEOXYRIBONUKLEOSIDEBORANOPHOSPHATE

Procedure for the representation of water-soluble Metallmercaptoverbindungen.

2,3 ' - O-CYCLOCYTIDINE ONES AND PROCEDURES FOR THEIR PRODUCTION.

PROCEDURE FOR REMOVING FROM TRITYL SCHUTZGRUPPEN FROM 5 ' - O-TRITYL-NUCLEOSIDES AND OLIGONUKLEOTIDEN.

MACRO EYELID ANTIBIOTIC DERIVATIVES.

EQUILATERAL REPEATED ONES SAMPLES AND IN THE SAME USING COMPOSITIONS.

PROCEDURE FOR THE PRODUCTION OF MODIFICATIONS OF INORGANIC POLYMERS, THEIR USE IN PROCEDURES FOR THE PRODUCTION OF POLYNUKLEOTIDEN AS WELL AS A REAGENT FOR USE IN THESE PROCEDURES.

ARTIFICIAL RECEPTOR-SIMILAR.

VERFAHREN ZUR HERSTELLUNG NEUER HYDROPHILER SILAN- UND SILOXANDERIVATE UND NACH DIESEM VERFAHREN HERGESTELLTE PRODUKTE

VERFAHREN ZUR HERSTELLUNG VON NEUEN ANTHRA- CYCLINGLYCOSIDEN

COMPLEX WITH OPTICALLY ACTIVE ONES SUGAR LIGANDS, PROCEDURES FOR THEIR PRODUCTION AND THEIR USE.

LOESLICHE PLATINUM (II) - COMPLEXES.

COLORED BRINE OF NON-METALLIC ELEMENTS OR CONNECTIONS, YOUR PRODUCTION AND USE.

TOPISCH OF ATTACHMENTS GOLDORGANOKOMPLEX.

PROCEDURE FOR THE SYNTHESIS OF TUBING SUGAR DERIVATIVES BY A REGIOKSELEKTIVE REACTION.

PROCEDURE FOR CONNECTING NUCLEOSIDES WITH SILOXANBRÜCKE.

PROCEDURE FOR the PRODUCTION OF 7-ACYLAMINO-3 (THIO SUBSTITUTED) METHYL-3-CEPHEM-4-CARBOXYLSAEURE-1 OXIDE CONNECTIONS.

PROCEDURE FOR THE PRODUCTION OF DEMETHYLEPYPODOPHYLLOTOXIN

IMPROVED PROCEDURE FOR the PRODUCTION OF 2 - AMINO (2,3,5-TRI-O-BENZYL-BETA-D ARABINOFURANOSYL) ADENINE

PROCEDURE FOR THE PRODUCTION OF METHYLCOBALAMIN

BORONSÄUREHALTIGE REAGENTS AND OLIGONUKLEOTIDE

PROCEDURE FOR THE PRODUCTION OF METHYLCOBALAMIN

PROCEDURE FOR THE SEPARATION AND/OR CLEANING OF OLIGO AND POLYHYDROXYVERBINDUNGEN

DEMONSTRABLY MARKER CONNECTION WITH A FLUOROPHOR REMAINDER MARKED, A FLUORESCENZ SAMPLE WITH THE MARKER CONNECTION AND USES THE SAME.

BABY FEEDING PREPARATION

METALLOCEN PHOSPHORAMIDIT KONJUGATE ONE, PROCEDURE FOR YOUR PRODUCTION AS WELL AS THEIR USE

PHARMACEUTICAL COMPOSITIONS FOR UNEASINESS REDUCTION

NUCLEOSIDES AND OLIGONUKLEOSIDE WITH THIOL GROUP

BIPHOTONIC PHOTOSENSITIZERS, NANOPARTICLES CONTAINING THE SAME AND THEIR USE AS DRUGS

The invention relates to compounds of formula (I) 5. Silica nanoparticle claim 1 , comprising at least one photosensitizer constituted by at least a compound according to claim 1 , covalently linked to said nanoparticle claim 1 , and possibly comprising shielding moieties grafted on the surface of said nanoparticle claim 1 , and possibly comprising biotargeting moieties grafted on the surface of said nanoparticle.6. Silica nanoparticle composition claim 1 , constituted by at least one silica nanoparticle comprising at least one photosensitizer constituted by at least a compound according to claim 1 , covalently linked to said nanoparticle claim 1 , and possibly comprising shielding moieties grafted on the surface of said nanoparticle claim 1 , and possibly comprising biotargeting moieties grafted on the surface of said nanoparticle.7. Silica nanoparticle composition according to claim 6 , wherein said silica nanoparticle have an organized porosity.8. Silica nanoparticle composition according to claim 6 , wherein said silica nanoparticle is mesoporous.9. Silica nanoparticle composition according to claim 6 , comprising biotargeting moieties grafted on the surface of said nanoparticle which specifically target neoplastic tissues.10. Silica nanoparticle composition according to claim 6 , comprising shielding moieties grafted on the surface of said nanoparticle claim 6 , and which specifically absorb radiations in the 190 to 600 nm range claim 6 , particularly in the 250 to 500 nm wavelengths.11. Silica nanoparticle composition according to claim 6 , wherein the concentration of said photosensitizer claim 6 , with respect to the total mass of the nanoparticle comprising said photosensitizer claim 6 , ranges from about 0.1 micromole per gram to about 100 micromoles per gram claim 6 , particularly ranges from about 0.5 micromoles per gram to about 30 micromoles per gram claim 6 , particularly ranges from about 1 micromoles per gram to about 10 micromoles per gram.12. ...

Fluorinated fructose derivatives for pet imaging

The present invention is directed to fructose-based radiopharmaceuticals, pharmaceutical compositions comprising same, precursors and methods for preparing same, and methods of using same for diagnostic imaging of cancer cells and non-imaging tracer studies.

NEW LOW MOLECULAR WEIGHT COMPLEXES BETWEEN IRON AND MALTOBIONIC ACID, USE THEREOF FOR INTRAMUSCULAR OR SUBCUTANEOUS ADMINISTRATION IN THE TREATMENT OF ANEMIC STATES, AND NEW PHARMACEUTICAL COMPOSITIONS ADAPTED FOR THESE USES

New low molecular weight complexes between iron and maltobionic acid that can be administered parenterally, preferably intramuscularly or subcutaneously, in the treatment of anemic states, caused by iron deficiencies, and new pharmaceutical compositions adapted for this use. In particular, the invention provides a new complex between preferably trivalent iron and maltobionic acid that is characterized by a molecular weight Mw between 10,000 and 30,000 Da, by a polydispersity of 1.0-1.8 and by an iron content between 25% and 40% by weight. 115-. (canceled)16. A complex between trivalent iron and maltobionic acid , characterized by a molecular weight Mw between 10 ,000 and 30 ,000 Da , by a polydispersity of 1.0-1.8 and by an iron content between 25% and 40% by weight.17. The complex according to claim 16 , characterized by a polydispersity of 1.0-1.6.18. The complex according to claim 16 , characterized by a molecular weight Mw between 12 claim 16 ,000 and 27 claim 16 ,000 Da claim 16 , by a polydispersity of 1.1-1.5 and by an iron content between 25% and 40% by weight.19. The complex according to claim 18 , characterized by a molecular weight Mw between 13 claim 18 ,000 and 18 claim 18 ,000 Da claim 18 , by a polydispersity of 1.2-1.4 and by an iron content between 25% and 40% by weight.20. The complex according to claim 19 , characterized by a molecular weight Mw between 13 claim 19 ,000 and 18 claim 19 ,000 Da claim 19 , by a polydispersity of 1.2-1.4 and by an iron content between 25% and 35% by weight.21. The complex according to claim 18 , characterized by a molecular weight Mw between 12 claim 18 ,000 and 27 claim 18 ,000 Da claim 18 , by a polydispersity of 1.1-1.5 and by an iron content between 26% and 32% by weight.22. The complex according to claim 20 , characterized by a molecular weight Mw between 13 claim 20 ,000 and 18 claim 20 ,000 Da claim 20 , by a polydispersity of 1.2-1.4 and by an iron content between 26.5% and 28.5% by weight.23. The complex ...

METHODS AND COMPOSITIONS RELATED TO MODIFIED ADENOSINES FOR CONTROLLING OFF-TARGET EFFECTS IN RNA INTERFERENCE

Disclosed are compositions and methods related to modified nucleobases. Also disclosed are compositions and methods related to modified interfering RNAs. Also disclosed are compositions and methods related to modified adenonsine for controlling off-target effects in RNA interference. 2. The compound of claim 1 , wherein Rcomprises a protected phosphate.4. The compound of claim 1 , wherein Ris chloride.8. The nucleoside of claim 7 , wherein Ris chloride.14. A method of blocking the binding of an off-target molecule to an siRNA molecule claim 7 , comprising claim 7 ,modifying at least one adenosine base of the siRNA molecule, andadministering to a subject the siRNA molecule.15. The method of claim 14 , wherein the siRNA molecule comprises two or more modified adenosine bases.16. The method of claim 14 , wherein the siRNA molecule comprises three or more modified adenosine bases.17. The method of claim 14 , wherein the modified adenosine base comprises the compound of .18. The method of claim 14 , wherein the off-target molecule is a double stranded RNA-binding motif (dsRBM).19. The method of claim 18 , wherein the dsRBM is RNA dependent protein kinase (PKR).20. The method of claim 18 , wherein the dsRBM is adenosine deaminase (ADAR).21. The method of claim 14 , wherein the off-target molecule is Toll-Like Receptor-7 claim 14 , Toll-Like Receptor-8 claim 14 , or Toll-Like Receptor-9.22. The method of claim 14 , wherein the efficacy of the siRNA molecule is increased.23. An siRNA molecule comprising at least one modified adenosine.24. The siRNA molecule of claim 23 , wherein the base opposite the modified adensosine is not complementary.25. A kit comprising the compound of .26. A kit comprising the compound of .27. A kit comprising the nucleoside of .28. A kit comprising the oligonucleotide of .29. A kit comprising the polynucleotide of .30. A set of nucleotides comprising at least one compound of .31. A set of nucleotides comprising at least one oligonucleotide or ...

COMPOSITION IN THE FORM OF LIQUID FOR MAINTENANANCE OF CONTACT LENSES AND MEDICAL MATERIALS

The invention relates to a composition, particularly in the form of liquid to be used externally as a rinsing contact lenses, containing nanocrystalline photocatalyst active in visible light, and optionally hydrogen peroxide. 2. The composition according to claim 1 , which is a colloidal solution having surface-modified titanium dioxide nanoparticles smaller than 100 nm as a dispersed phase claim 1 , and the solution of hydrogen peroxide as the dispersing medium.3. The composition according to claim 1 , characterized in that it shows visible light absorption in the wavelength range (λ) of not less than approximately 400 nm to about 600 nm claim 1 , preferably up to about 700 nm claim 1 , and ultraviolet light absorption (λ<400 nm).4. The composition according to claim 1 , wherein the organic compound is a compound selected from the group consisting of: phthalic acid claim 1 , 4-sulfophthalic acid claim 1 , 4-amino-2-hydroxybenzoic acid claim 1 , 3-hydroxy-2-naphthylic acid claim 1 , salicylic acid claim 1 , 6-hydroxysalicylic acid claim 1 , 5-hydroxysalicylic acid claim 1 , 5-sulfosalicylic acid claim 1 , 3 claim 1 ,5-dinitrosalicylic acid claim 1 , disodium salt of 1 claim 1 ,4-dihydroxy-1 claim 1 ,3-benzenedisulfonic acid claim 1 , gallic acid claim 1 , pyrogallol claim 1 , 2 claim 1 ,3-naphthalenediol claim 1 , 4-methylcatechol claim 1 , 3 claim 1 ,5-di-tert-butylcatechol claim 1 , p-nitrocatechol claim 1 , 3 claim 1 ,4-dihydroxy-L-phenylalanine (DOPA) claim 1 , rutin and ascorbic acid.5. The composition according to claim 2 , characterized in that it exhibits stability in aqueous solution with a pH of about 7 claim 2 , and wherein the organic compound is a compound selected from the group consisting of: disodium salt of 4 claim 2 ,5-dihydroxybenzene-1 claim 2 ,3-disulfonic acid claim 2 , rutin and ascorbic acid.6. The composition according to claim 1 , further comprising a buffer system claim 1 , preferably isotonic claim 1 , to maintain the pH in a ...

METAL PARTICLES FOR SURFACE-ENHANCED RAMAN SCATTERING AND MOLECULAR SENSING

There is provided a high-sensitive Raman scattering sensing by regulating in metal nanoparticles for enhanced Raman scattering, particularly the strength of the enhanced electric field by controlling the distance between the particles to impart very strong Raman scattering properties. A metal nanoparticle material for molecular sensing, the metal nanoparticle material comprising: a metal nanoparticle aggregate including three to ten metal nanoparticles connected to each other through an organic molecule so that adjacent metal nanoparticles are bonded and spaced apart a predetermined distance, the aggregate containing a Raman active molecule within a field applied to the aggregate, wherein the metal nanoparticle material emits enhanced Raman scattering light from the Raman active molecule in an enhanced electric field; a method for producing the metal nanoparticle material for molecular sensing; and a molecular sensing by use of the metal nanoparticle material for molecular sensing. 1. A metal nanoparticle material for molecular sensing , the metal nanoparticle material comprising:a metal nanoparticle aggregate including three to ten metal nanoparticles connected to each other through an organic molecule so that adjacent metal nanoparticles are bonded and spaced apart a predetermined distance, the aggregate containing a Raman active molecule within a field applied to the aggregate, whereinthe metal nanoparticle material emits enhanced Raman scattering light from the Raman active molecule in an enhanced electric field.2. The metal nanoparticle material for molecular sensing according to claim 1 , wherein the metal nanoparticles are of a metallic element having a resonance wavelength producing surface plasmon resonance in regions ranging from an ultraviolet region to an infrared region.3. The metal nanoparticle material for molecular sensing according to claim 1 , wherein the metal nanoparticles are particles having an average particle diameter of 1 nm to 100 nm.4. The ...

NUCLEOTIDES AND APTAMERS CONTAINING BORONIC ACID GROUPS HAVING BIASED BINDING TO GLYCOSYLATED PROTEINS, AND USES THEREOF

The present disclosure encompasses oligonucleotide aptamers selectively binding a target glycosylated polypeptide or protein, and having biased affinity for the glycan through a boronic acid linked to a nucleosidic base of a nucleotide(s). The disclosure further encompasses methods for isolating an aptamer(s) selectively binding a target glycosylated polypeptide, where, from a population of randomized oligonucleotides that have at least one nucleotide having a boronic acid label linked to a base, is selected a first subpopulation of aptamers binding to the target glycosylated polypeptide or protein. This subpopulation is then amplified without using boronic acid-modified TTP, and amplification products not binding to a target glycosylated polypeptide or protein are selected. The second subpopulation of aptamers is then amplified using boronic acid-modified TTP to provide a population of boronic acid-modified aptamers capable of selectively binding to a glycosylation site of a target polypeptide or protein. Other aspects of the disclosure encompass methods for the use of the modified aptamers to detect glycosylated species of a polypeptide or protein. 2. The nucleotide monomer of claim 1 , further comprising a tether linking Rand R.3. The nucleotide monomer of claim 1 , wherein Ris thymine claim 1 , Ris OH claim 1 , and Ris H.4. The nucleotide monomer of claim 1 , wherein Ris a boronic acid selected from the group consisting of: a phenylboronic acid claim 1 , a naphthalenylboronic acid claim 1 , a quinolinylboronic acid claim 1 , a pyridinylboronic acid claim 1 , a furanylboronic acid claim 1 , a thiophenylboronic acid claim 1 , an indolylboronic acid claim 1 , a 1 claim 1 ,8-naphthalimide-based boronic acid claim 1 , an α-acetaminoalkylboronic acid claim 1 , a quinolin-4-ylboronic acid claim 1 , a quinolin-5-ylboronic acid claim 1 , a quinolin-8-ylboronic acid claim 1 , a pyridinylboronic acid claim 1 , a furan-2-ylboronic acid claim 1 , and a thiophen-2-ylboronic ...

Asymmetric biofunctional silyl monomers and particles thereof as prodrugs and delivery vehicles for pharmaceutical, chemical and biological agents

Asymmetric bifunctional silyl (ABS) monomers comprising covalently linked pharmaceutical, chemical and biological agents are described. These agents can also be covalently bound via the silyl group to delivery vehicles for delivering the agents to desired targets or areas. Also described are delivery vehicles which contain ABS monomers comprising covalently linked agents and to vehicles that are covalently linked to the ABS monomers. The silyl modifications described herein can modify properties of the agents and vehicles, thereby providing desired solubility, stability, hydrophobicity and targeting.

PURIFICATION OF SYNTHETIC OLIGONUCLEOTIDES

This invention provides a method for purifying synthetic oligonucleotides comprising capping, polymerizing and separating any failure sequences produced during oligonucleotide synthesis. The invention also provides a method for purifying synthetic oligonucleotides comprising reacting a full length oligonucleotide with a compound to attach a polymerizable functional group to an end of the full length oligonucleotide, polymerizing the full length oligonucleotides and removing the failure sequences, and recovering the full length oligonucleotides. The invention also provides novel capping agents having a polymerizable functional group, and kits comprising at least one composition of the present invention. 2. The method of claim 1 , wherein Ris hydrogen.5. The method of claim 4 , wherein Ar is 1 claim 4 ,4-phenylenyl.6. The method of claim 4 , wherein Y is —O—.7. The method of claim 1 , wherein the failure sequences are polymerized via radical acrylamide polymerization.8. The method of claim 1 , wherein linker is (CH).9. The method of claim 1 , wherein Ris —N(CH(CH)).10. The method of claim 1 , wherein Ris —CH—-CH—CN.11. The method of claim 1 , wherein Ris methyl.12. The method of claim 1 , wherein Rand Rare each hydrogen.14. The method of claim 13 , wherein Rand Rare each hydrogen.17. The method of claim 16 , wherein Ris hydrogen.18. The method of claim 16 , wherein Ar is 1 claim 16 ,4-phenylenyl.19. The method of claim 16 , wherein Y is —O—.20. The method of claim 13 , wherein linker is (CH).22. The method of claim 21 , wherein Ris hydrogen.25. The method of claim 24 , wherein Ar is 1 claim 24 ,4-phenylenyl.26. The method of wherein Y is —O—.28. The method of claim 27 , wherein Ris hydrogen.29. The method of claim 27 , wherein Y is —O—.32. The method of claim 31 , wherein Ar is 1 claim 31 ,4-phenylenyl.33. The method of claim 31 , wherein Y is —O—.34. The method of claim 31 , wherein Z is —O—.36. The method of claim 13 , wherein Ris —N(CH(CH)).37. The method of claim ...

METHODS AND COMPOSITIONS FOR ADMINISTRATION OF IRON

The present invention generally relates to treatment of iron-related conditions with iron carbohydrate complexes. One aspect of the invention is a method of treatment of iron-related conditions with a single unit dosage of at least about 0.6 grams of elemental iron via an iron carbohydrate complex. The method generally employs iron carbohydrate complexes with nearly neutral pH, physiological osmolarity, and stable and non-immunogenic carbohydrate components so as to rapidly administer high single unit doses of iron intravenously to patients in need thereof. 1. A method of treating a disease , disorder , or condition characterized by iron deficiency or dysfunctional iron metabolism resulting in reduced bioavailability of dietary iron , comprisingadministering to a subject in need thereof an iron carbohydrate complex in a single dosage unit of at least about 0.6 grams of elemental iron; 'the iron carbohydrate complex is selected from the group consisting of an iron carboxymaltose complex, an iron mannitol complex, an iron polyisomaltose complex, an iron polymaltose complex, an iron gluconate complex, an iron sorbitol complex, and an iron hydrogenated dextran complex.', 'wherein'}2. The method of claim 1 , wherein the iron carbohydrate complex has a substantially non-immunogenic carbohydrate component.3. The method of claim 1 , wherein the iron carbohydrate complex has substantially no cross reactivity with anti-dextran antibodies.4. The method of claim 1 , wherein the disease claim 1 , disorder claim 1 , or condition comprises anemia.5. The method of claim 4 , wherein the anemia comprises iron deficiency anemia.6. The method of claim 4 , wherein:(i) the anemia comprises an iron deficiency anemia associated with chronic blood loss; acute blood loss; pregnancy; childbirth; childhood development; psychomotor and cognitive development in children; breath holding spells; heavy uterine bleeding; menstruation; chronic recurrent hemoptysis; idiopathic pulmonary siderosis; ...

TARGETED SCHIFF BASE COMPLEXES

The present invention provides targeted Schiff base complexes. In particular the present invention provides biopolymer targeted transition metal complexes configured to inhibit the activity of targeted proteins, methods of synthesis thereof, and pharmaceutical compositions and uses thereof. 2. The composition of claim 1 , wherein said biopolymer comprises nucleic acid.3. The composition of claim 2 , wherein said nucleic acid comprises the binding site for a DNA binding protein.4. The composition of claim 1 , wherein Rcomprises an attachment site for said linker claim 1 , and each of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rcomprise hydrogen.5. The composition of claim 1 , wherein the coordinated transition metal is selected from nickel claim 1 , cadmium claim 1 , zinc claim 1 , iron and cobalt.6. The composition of claim 5 , wherein said coordinated transition metal comprises cobalt.7. The composition of claim 1 , further comprising one or more axial ligands complexed with the transition metal X.9. The composition of claim 8 , wherein said linker comprises the structure of Formula 1.10. The composition of claim 8 , wherein said nucleic acid comprises a binding site for a DNA binding protein.11. The composition of claim 9 , wherein said nucleic acid comprises a binding site for a transcription factor.12. The composition of claim 10 , wherein said nucleic acid comprises a binding site for Snail family transcription factors.13. The composition of claim 11 , wherein said nucleic acid comprises a first DNA oligonucleotide comprising the Ebox consensus sequence CAGGTG and a second DNA oligonucleotide comprising the complementary sequence CACCTG.14. The composition of claim 8 , further comprising one or more axial ligands complexed with said cobalt.15. A method of inhibiting a protein comprising contacting said protein with a composition of .16. The method of claim 15 , wherein said protein comprises a DNA binding domain.17. The method ...

NUCLEIC ACID CONSTRUCT AND METHOD OF PREPARING NANOPARTICLE USING THE SAME

A nucleic acid construct, a method of preparing a nanoparticle by using the nucleic acid construct, and a nanoparticle and nanoparticle complex prepared using the method. Various types of metal nanoparticles may be efficiently prepared using the template for preparing a nanoparticle and the nanoparticle prepared using the template. 1. A nanoparticle comprising a metal ion or a metal precursor , and a nucleic acid construct ,wherein the nucleic acid construct comprises at least two single-stranded nucleic acids, each of the at least two single-stranded nucleic acids comprising at least ten nucleotides and at least two adjacent segments, wherein each of the entire segments is complementary to one of the remainder segments, and wherein the segments are hybridized to their respective substantially complementary segments so that the nucleic acid construct comprises a plurality of double-stranded segments; andwherein the metal ion or metal precursor is bound to a phosphate backbone of the nucleic acid construct or to a base of the nucleic acid construct.2. The nanoparticle of claim 1 , wherein a metal of the metal ion or the metal precursor is selected from the group consisting of gold claim 1 , silver claim 1 , copper claim 1 , platinum claim 1 , palladium claim 1 , and combinations thereof.3. The nanoparticle of claim 1 , wherein the nucleic acid construct comprises 2 to 10 single-stranded nucleic acids.4. The nanoparticle of claim 1 , wherein each of the at least two single-stranded nucleic acids comprises 2 to 5 segments.5. The nanoparticle of claim 1 , wherein the nucleic acid construct comprises at least one cross-linking or intercalating agent between two nucleic acid strands where segments are substantially complementarily bound to each other.6. The nanoparticle of claim 1 , wherein the adjacent segments do not comprise a linker claim 1 , or further comprise a linker consisting of 1 to 50 nucleotides that do not complementarily bind to any one of the at least two ...

URIDINE DI- OR TRI-PHOSPHATE DERIVATIVES AND USES THEREOF

The invention provides particular uridine di- and tri-phosphate derivatives, and pharmaceutical compositions thereof. These compounds are useful for treatment of diseases, disorders and conditions modulated by P2Y6 receptors, and particularly for lowering intraocular pressure and thereby treating ocular hypertension and/or glaucoma. 2. The compound of claim 1 , wherein R is —O—(C-C)alkyl or —S—(C-C)alkyl.3. The compound of claim 1 , wherein R is —O—(C-C)alkyl or —S—(C-C)alkyl.4. The compound of claim 1 , wherein n is 0 claim 1 , and at least one of Zand Zis BH; or n is 1 claim 1 , and at least one of Zto Zis BH.5. The compound of claim 4 , wherein n is 0 claim 4 , and (i) Zis BH claim 4 , and Zis O; (ii) Zis BH claim 4 , and Zis O; or (iii) Zand Zare BH.6. The compound of claim 4 , wherein n is 1 claim 4 , and (i) Zis BH claim 4 , and Zand Zare O; (ii) Zis BH claim 4 , and Zand Zare O; (iii) Zis BH claim 4 , and Zand Zare O; (iv) Zand Zare BH claim 4 , and Zis O; (v) Zand Zare BH claim 4 , and Zis O; (vi) Zand Zare BH claim 4 , and Zis O; or (vii) Zto Zare BH.7. The compound of claim 1 , wherein R is —O—(C-C)alkyl claim 1 , n is 0 claim 1 , and (i) Zis BH claim 1 , and Zis O; (ii) Zis O claim 1 , and Zis BH; or (iii) Zand Zare BH.8. The compound of claim 7 , wherein R is —OCH claim 7 , Y each is —OH claim 7 , n is 0 claim 7 , Zis BH claim 7 , and Zis O claim 7 , herein identified compound 13.9. The compound of claim 8 , characterized by being the isomer with a retention time (R) of 8.97 min when separated from a mixture of diastereoisomers using a semi-preparative reverse-phase Gemini 5μ column (C-18 110 A claim 8 , 250×10 mm claim 8 , 5 micron) claim 8 , and isocratic elution [100 mM triethylammonium acetate claim 8 , pH 7: CHCN claim 8 , 94:6] with flow rate of 5 ml/min claim 8 , herein identified compound 13A.10. The compound of claim 7 , wherein R is —OCH claim 7 , Y each is —OH claim 7 , n is 1 claim 7 , Zis BH claim 7 , and Zand Zis O claim 7 , herein ...

Compositions for the Treatment or Prophylaxis of Viral Infections

A compound of the general formula (III): wherein X is O, S, NH or CH; Y is O, S or NH; Z is O, S or CH; Ris Calkyl, especially Calkyl, preferably n-alkyl, e.g., n-pentyl or n-hexyl; at least one of Rand Ris H—[R—R]—R—, in which: H—[R—R]— comprises an oligopeptide, Rbeing an amino acid and Rbeing an amino acid selected from proline, alanine, hydroxyproline, dihydroxyproline, thiazolidinecarboxylic acid (thioproline), dehydroproline, pipecolic acid (L-homoproline), azetidinecarboxylic acid, aziridinecarboxylic acid, glycine, serine, valine, leucine, isoleucine and threonine, Ris a neutral, non-polar amino acid moiety that is bonded to Rby a peptide bond, and n is 1, 2, 3, 4 or 5; and the other of Rand Ris H—[R—R]n-R— or H; or a pharmaceutically acceptable salt thereof. 2. The method of claim 1 , wherein 100-500 mg of said compound is administered once daily (s.i.d.).3. The method of claim 1 , wherein said compound is administered with a pharmaceutically acceptable excipient.4. The method of claim 1 , wherein one of Rand Ris H—[R—R]—R— and the other is H.5. The method of claim 1 , wherein both of Rand Ris H—[R—R]—R—.6. The method of claim 5 , wherein Rand Rare the same.7. The method of claim 1 , wherein n=1.8. The method of claim 1 , wherein Ris selected from alanine claim 1 , arginine claim 1 , asparagine claim 1 , aspartic acid claim 1 , cysteine claim 1 , glutamine claim 1 , glutamic acid claim 1 , glycine claim 1 , histidine claim 1 , isoleucine claim 1 , leucine claim 1 , lysine claim 1 , methionine claim 1 , phenylalanine claim 1 , proline claim 1 , serine claim 1 , threonine claim 1 , tryptophan claim 1 , tyrosine and valine claim 1 , preferably valine.9. The method of claim 1 , wherein Ris selected from proline claim 1 , alanine claim 1 , glycine claim 1 , serine claim 1 , valine and leucine claim 1 , preferably proline or alanine.10. The method of claim 1 , wherein the oligopeptide —[R—R]— is selected from Val-Pro claim 1 , Asp-Pro claim 1 , Ser-Pro claim 1 , ...

URIDINE-BASED GADOLINIUM COMPLEX AND MRI CONTRAST AGENT INCLUDING THE SAME

The present invention relates to a new uridine nucleoside-based amphiphilic gadolinium complex and a magnetic resonance imaging (MRI) contrast agent including the gadolinium complex. The MRI contrast agent has high relaxivity, high binding affinity for and stability in human serum albumin, pH response, and high liver specificity. 2. The uridine-based gadolinium complex according to claim 1 , wherein n is at least 6.8. An MRI contrast agent comprising the uridine-based gadolinium complex of Formula 1 according to .9. The MRI contrast agent according to claim 8 , wherein the MRI contrast agent is used for the diagnosis of liver abnormalities.10. The MRI contrast agent according to claim 8 , wherein the MRI contrast agent is in the form of an intravenous injection. The present invention relates to a new gadolinium complex and a magnetic resonance imaging (MRI) contrast agent including the same. More specifically, the present invention relates to a uridine-based MRI contrast agent that has high relaxivity, high binding affinity for and stability in human serum albumin, pH response, and high liver specificity.Magnetic resonance imaging (MRI) is a powerful noninvasive technique that provides high quality three dimensional images of tissues, including information on anatomy, function, and metabolism of tissue in vivo.The chelated Gd metal ion improves image contrast by decreasing the longitudinal relaxation time (T1) of proximal water protons, which appear brighter in the T1-weighted MR image. Current advanced medical diagnosis techniques stipulate high-resolution images with a high magnetic field scanner.However, current Gd-based contrast agents are incapable of meeting requirements as they do not have optimal relaxivity profiles at high magnetic fields. This requirement drives the research for smart contrast agents with high relaxivities (r1) for better tissue contrast at high magnetic fields and non-covalent binding affinity for human serum albumin (HSA) to enhance in ...

1,2,3-Triazolyl Purine Derivatives

The present invention relates to novel 1,2,3-triazolyl purine derivatives. The invention also relates to using the derivatives to treat cancer and various viral infections. An example of a 1,2,3-triazolyl purine derivative of the invention is

Synthetic Lipid A Derivative

The invention provides functionalized monosaccharides and disaccharides suitable for use in synthesizing a lipid A derivative, as well as methods for synthesizing and using a synthetic lipid A derivative. 2. The compound of wherein Ris tert-butyldimethylsilyl (TBS) or dimethylthexylsilyl (TDS).3. The compound of wherein Ris azido.4. The compound of wherein Ris an amino protecting group comprising 9-fluorenylmethoxycarbamate (Fmoc).5. The compound of wherein Ris a hydroxyl protecting group comprising allyloxycarbonate (Alloc).6. The compound of wherein Ris an amino protecting group comprising 9-fluorenylmethoxycarbamate (Fmoc).7. The compound of wherein Ris a hydroxyl protecting group comprising allyloxycarbonate (Alloc) or levulinate (Lev).8. The compound of wherein Rand Rtogether form a ring comprising an acetal.10. The method of wherein selectively acylating the functionalized disaccharide comprises selectively acylating the functionalized disaccharide at two claim 9 , three or four of positions C-2 claim 9 , C-3 claim 9 , C-2′ and C-3′ of the functionalized disaccharide.11. The method of further comprising phosphorylating the functionalized disaccharide at either or both of the C-1 or C-4′ positions of the functionalized disaccharide.12. The method of further comprising contacting the functionalized disaccharide with a 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) donor to yield a KDO glycoside at the C-6′ position of the functionalized disaccharide.13. The method of wherein Ris tert-butyldimethylsilyl (TBS) or dimethylthexylsilyl (TDS).14. The method of wherein Ris azido.15. The method of wherein Ris an amino protecting group comprising 9-fluorenylmethoxycarbamate (Fmoc).16. The method of wherein Ris a hydroxyl protecting group comprising allyloxycarbonate (Alloc). This application is a continuation application of U.S. application Ser. No. 12/676,253, filed Apr. 19, 2010, which is national stage application of International Application No. PCT/US2008/010394, filed ...

Synthesis of deuterated ribo nucleosides N-protected phosphoramidites, and oligonucleotides

The present invention is directed towards the synthesis of high purity deuterated sugars, deuterated phosphoramidites, deuterated nucleobases, deuterated nucleosides, deuterated oligonucleotides, and deuterated RNA's of defined sequences which can exhibit biochemically useful and biologically valuable properties, thus having potential for therapeutic uses. 2. The modified phosphoramidite according to wherein said R1 is dimethoxytrityl protecting group claim 1 , R2 is t-butyldimethylsilyl protecting group claim 1 , R3 is diiopropylamino protecting group claim 1 , and R4 is a 3′-O-cyanoethyl protecting group.3. The modified phosphoramidite according to wherein said B contains a blocking group.4. The modified phosphoramidite according to wherein said nucleobase is a natural base.5. The modified phosphoramidite according to wherein said natural base is adenine.6. The modified phosphoramidite according to wherein said natural base is guanine.7. The modified phosphoramidite according to wherein said natural base is cytosine.8. The modified phosphoramidite according to wherein said natural base is uracil.9. The modified phosphoramidite according to wherein said nucleobase is a modified nucleobase.10. The modified phosphoramidite according to wherein said modified base is deuteratedadenine.11. The modified phosphoramidite according to wherein said modified base is deuteratedguanine12. The modified phosphoramidite according to wherein said modified base is deuteratedcytosine.13. The modified phosphoramidite according to wherein said modified base is deuterateduracil.14. The modified oligonucleotide according to wherein the ribose sugar is partially deuterated.16. The deuterated oligonucleotide solid support according to wherein said R1 is dimethoxytrityl protecting group claim 15 , R2 is t-butyldimethylsilyl protecting group claim 15 , R4 is succinyl Icaa claim 15 , and R4 is CPG.17. The deuterated oligonucleotide solid support according to wherein said nucleobase is a ...

GLUCOPYRANOSYL-SUBSTITUTED PHENYL DERIVATES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR MANUFACTURE

Glucopyranosyl-substituted benzene derivatives of general formula I 122.-. (canceled)24. Process according to claim 23 , wherein the organometallic compound (V) is a lithium or magnesium compound.25. (canceled) This application claims benefit of under 35 U.S.C. 119(e) filed No. 60/560,239 Apr. 7, 2004, from German application number DE1 02004 012676.3 filed Mar. 16, 2004, from German application number DE102004040168.3 filed Aug. 18, 2004, and from German application number DE102004061145.9 filed Dec. 16, 2004, the contents of which are incorporated herein.The present invention relates to glucopyranosyl-substituted benzene derivatives of general formula Iwherein the groups Rto Rand R, R, Rare as defined hereinafter, including the tautomers, the stereoisomers, the mixtures thereof and the salts thereof. The invention further relates to pharmaceutical compositions containing a compound of formula I according to the invention as well as the use of a compound according to the invention for preparing a pharmaceutical composition for the treatment of metabolic disorders. In addition, the invention relates to processes for preparing a pharmaceutical composition as well as a compound according to the invention.In the literature, compounds which have an inhibitory effect on the sodium-dependent glucose cotransporter SGLT2 are proposed for the treatment of diseases, particularly diabetes.Glucopyranosyloxy-substituted aromatic groups and the preparation thereof and their possible activity as SGLT2 inhibitors are known from published International applications WO 98/31697, WO 01/27128, WO 02/083066, WO 03/099836, WO 2004/063209, WO 2004/080990, WO 2004/013118, WO 2004/052902, WO 2004/052903 and US application US 2003/0114390.The aim of the present invention is to find new pyranosyloxy-substituted benzene derivatives, particularly those which are active with regard to the sodium-dependent glucose cotransporter SGLT, particularly SGLT2. A further aim of the present invention is ...

NEW BORANOPHOSPHATE ANALOGUES OF CYCLIC NUCLEOTIDES

The present invention relates to novel boranophosphate analogues of cyclic nucleotides. The invention further relates to the use of such compounds as reagents for signal transduction research or as modulators of cyclic nucleotide-regulated binding proteins and isoenzymes thereof, and/or as hydrolysis- and oxidation-resistant ligands for affinity chromatography, for antibody production or for diagnostic applications e.g. on chip surfaces and/or as additive for organ transplantation storage solutions. 3. The compound of claim 1 , whereinR1 is H, F, Cl, Br, I, azido, nitro, 2-furyl, 3-furyl, 2-bromo-5-furyl, 2-thienyl, 3-thienyl, allyl, trifluoromethyl, phenyl, OH, methoxy, ethoxy, n-propoxy, n-butoxy, benzyloxy, 4-methylbenzyloxy, 4-methoxybenzyloxy, 4-fluorobenzyloxy, 4-chlorobenzyloxy, 4-bromobenzyloxy, phenyloxy, SH, methylthio, ethylthio, n-propylthio, n-butylthio, n-pentylthio, n-hexylthio, isopropylthio, 2-hydroxyethylthio, 2-aminoethylthio, 2-carboxyethylthio, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)ethylthio, (4-bromo-2,3-dioxobutyl)thio, [2-[(fluoresceinylthioureido)amino]ethyl]thio, cyclohexylthio, benzylthio, 4-azidobenzylthio, phenylthio, 2-chlorophenylthio, 3-chlorophenylthio, 4-chlorophenylthio, 2-bromophenylthio, 3-bromophenylthio, 4-bromophenylthio, 2-fluorophenylthio, 3-fluorophenylthio, 4-fluorophenylthio, 4-nitrophenylthio, 2-aminophenylthio, 3-aminophenylthio, 4-aminophenylthio, phenylethylamino, 3-phenyl-propylamino, 2-methoxyphenylthio, 3-methoxyphenylthio, 4-methoxyphenylthio, 2-methylphenylthio, 3-methylphenylthio, 4-methylphenylthio, 2-isopropylphenylthio, 4-isopropylphenylthio, 2,3,5,6-tetrafluorophenylthio, 4-hydroxyphenylthio, 2,3-dichlorophenylthio, 2,4-dichlorophenylthio, 2,5-dichlorophenylthio, 2,4-difluorophenylthio, 2,5-dimethoxyphenylthio, 2,5-dimethylthiophenylthio, 2,6-dimethylthiophenylthio, 2,6-dichlorophenylthio, 4-isopropyloxyphenylthio, 4-methylthiophenylthio, 4-azidophenylthio, 4-methylcumarinyl, naphtyl-2-thio, 4- ...

SUBSTRATES COMPRISING SWITCHABLE FERROMAGNETIC NANOPARTICLES

In a process for producing organic substrate particles bonded to switchable ferromagnetic nanoparticles with a mean particle diameter in the range from 10 to 1000 nm, the ferromagnetic nanoparticles used are those nanoparticles which are nonferromagnetic at first, but become ferromagnetic when the temperature is lowered, these at first nonferromagnetic nanoparticles in dispersed form are bonded to the organic substance particles, and then the nanoparticles bonded to the substrate particles are made ferromagnetic as a result of the temperature being lowered. 1. (canceled)2. Diagnostic substrate particles , which comprise organic substrate particles bonded to switchable ferromagnetic nanoparticles with a mean particle diameter in the range from 10 to 1000 nm , said substrate particles having a specific bonding action for a substance to be analyzed.3. Diagnostic substrate particles according to claim 2 , which comprise switchable nanoparticles with a mean particle diameter in the range from 10 to 1000 nm claim 2 , wherein the switchable nanoparticles are in a nonferromagnetic state during a bonding of organic substrate to said switchable nanoparticles claim 2 , and the switchable nanoparticles are nanoparticles that have not been switched to the ferromagnetic state by a first cooling of the nanoparticles prior to said bonding.4. A medicament for hyperthermia treatment in the human or animal body claim 2 , comprising switchable ferromagnetic nanoparticles with a mean particle diameter in the range from 10 to 1000 nm claim 2 , which become ferromagnetic when the temperature is lowered.5. The medicament according to claim 4 , wherein the switchable ferromagnetic nanoparticle is magnetocaloric.6. The medicament according to for cancer treatment.7. Diagnostic substrate particles according to claim 2 , which are obtained by a process comprising bonding an organic substrate compound to switchable nanoparticles with a mean particle diameter in the range from 10 to 1000 nm ...

METHODS AND COMPOSITIONS FOR ADMINISTRATION OF IRON

The present invention generally relates to treatment of iron-related conditions with iron carbohydrate complexes. One aspect of the invention is a method of treatment of iron-related conditions with a single unit dosage of at least about 0.6 grams of elemental iron via an iron carbohydrate complex. The method generally employs iron carbohydrate complexes with nearly neutral pH, physiological osmolarity, and stable and non-immunogenic carbohydrate components so as to rapidly administer high single unit doses of iron intravenously to patients in need thereof. 1. A method of treating a disease , disorder , or condition characterized by iron deficiency or dysfunctional iron metabolism resulting in reduced bioavailability of dietary iron , comprisingadministering to a subject in need thereof an iron carbohydrate complex in a single dosage unit of at least about 0.6 grams of elemental iron; 'the iron carbohydrate complex is selected from the group consisting of an iron carboxymaltose complex, an iron mannitol complex, an iron polyisomaltose complex, an iron polymaltose complex, an iron gluconate complex, an iron sorbitol complex, and an iron hydrogenated dextran complex.', 'wherein'}2. The method of claim 1 , wherein the iron carbohydrate complex has a substantially non-immunogenic carbohydrate component.3. The method of claim 1 , wherein the iron carbohydrate complex has substantially no cross reactivity with anti-dextran antibodies.4. The method of claim 1 , wherein the disease claim 1 , disorder claim 1 , or condition comprises anemia.5. The method of claim 4 , wherein the anemia comprises iron deficiency anemia.6. The method of claim 4 , wherein:(i) the anemia comprises an iron deficiency anemia associated with chronic blood loss; acute blood loss; pregnancy; childbirth; childhood development; psychomotor and cognitive development in children; breath holding spells; heavy uterine bleeding; menstruation; chronic recurrent hemoptysis; idiopathic pulmonary siderosis; ...

LIPID-BASED PLATINUM COMPOUNDS AND NANOPARTICLES

The present disclosure is in relation to the field of nanotechnology and cancer therapeutics. In particular, the present disclosure relates to platinum based compounds comprising platinum moiety, linker moiety and lipid moiety and corresponding nanoparticles thereof. The disclosure further relates to synthesis of said platinum based compounds, nanoparticles and compositions comprising said platinum based compounds/nanoparticles. The disclosure also relates to methods of managing cancer by employing aforesaid carbene compounds, platinum based compounds, nanoparticles and compositions thereof. 1. A compound comprising:(a) a platinum moiety; and(b) a lipid connected to said platinum moiety.2. The compound of claim 1 , wherein the compound comprises a carbonyl moiety.3. The compound of claim 2 , wherein the carbonyl moiety is a carboxylic acid that is succinic acid claim 2 , malonic acid claim 2 , oxalic acid claim 2 , keto acid claim 2 , or a combination thereof4. The compound of claim 1 , wherein the platinum moiety comprises a platinum atom that is conjugated to said lipid via covalent bond claim 1 , coordinate bond or a combination thereof.5. The compound of claim 1 , further comprising at least one linker between the platinum moiety and the lipid.7. The compound of claim 1 , wherein the linker is:{'sub': 2', '2', '1, 'claim-text': X is NH;', {'sub': 1', '2, 'Xis C(O)O, C(O)NH, O(CH)—O, NH, or O;'}, {'sub': 2', '2', 'n, 'Xis (CH)or C(O); and'}, 'n is 0, 1, 2, 3, 4, or 5;, '(i) —X—CH—X—X—, wherein{'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'm', '2', 'n', '2', 'm', '2', 'n', '2', 'n', '2', 'm', '2', 'n, 'claim-text': 'wherein, n and m are, independently, 0, 1, 2, 3, 4, or 5;', '(ii) —(CH)O—, —(CH)NHC(O)O—, —(CH)OC(O)NH—, —(CH)C(O)NH(CH)O—, —(CH)O(CH)O—, —(CH)OC(O)—, (CH)NHC(O)(CH)O—, or —(CH)C(O)O—;'}{'sub': 3', '4', '5', '6, 'claim-text': [{'sub': 3', '2, 'Xis CH, CH, or O; and'}, {'sub': 4', '5', '6', '2, 'X, Xand Xare, independently, —CHO— or O; or'}], '( ...

SEPARATION OF OLIGOSACCHARIDES FROM FERMENTATION BROTH

The present invention relates to the isolation and purification of sialylated oligosaccharides from an aqueous medium in which they are produced. 1. A method for separating a sialylated oligosaccharide from an aqueous medium , the method comprising treating an aqueous medium containing said sialylated oligosaccharide with a strong anion exchange resin in Cl-form and a strong cation exchange resin.2. The method of claim 1 , wherein said aqueous medium is a fermentation broth or an enzymatic reaction mixture containing said sialylated oligosaccharide.3. The method of claim 1 , wherein the separated sialylated oligosaccharide is obtained in the form of its alkali metal salt.4. The method of claim 1 , wherein the strong cation exchange resin is in an alkali metal cation form or H-form.5. The method of claim 1 , further comprising neutralizing an eluate of the strong cation resin in H-form with an alkali metal containing basic solution.6. The method of claim 1 , wherein said treating of said aqueous medium with said strong cation exchange resin follows treating said aqueous medium with said strong anion exchange resin.7. The method of claim 2 , wherein said fermentation broth is obtained by culturing a genetically modified cell claim 2 , wherein said cell is capable of producing said sialylated oligosaccharide from an internalized carbohydrate precursor.8. The method of claim 1 , wherein said sialylated oligosaccharide is a sialylated lactose.9. The method of claim 8 , wherein said sialylated lactose is 3′-SL or 6′-SL.1012-. (canceled)13. The method of claim 6 , wherein said treating of said aqueous medium with said strong cation exchange resin immediately follows treating said aqueous medium with said strong anion resin.14. The method of claim 7 , wherein said genetically modified cell is from a genetically modified microorganism.15E. coli,E. coli. The method of claim 14 , wherein said genetically modified microorganism is an wherein the contains one or more ...

Ultrastable Silver Nanoparticles

Ultrastable silver nanoparticles, methods of making the same, and methods of using the same, are disclosed. 1. A compound comprising the formula MAg(SR)wherein:M is a metal selected from the group consisting of Cs, Na, K, Li, Fr, and Rb; andSR is a mercaptophenyl ligand;and salts, isomers, stereoisomers, entantiomers, racemates, solvates, hydrates, polymorphs, and prodrugs thereof.2. The compound of claim 1 , wherein the mercaptophenyl ligand is selected from the group consisting of p-mercaptobenzoic acid claim 1 , p-mercaptophenyl alcohol claim 1 , and 4-mercaptophenol.3. (canceled)4. The compound of claim 1 , further comprising coordinating molecules selected from the group consisting of: deprotonated methanol ions claim 1 , deprotonated ethanol ions claim 1 , hydroxide ions claim 1 , citrate claim 1 , acetate claim 1 , DMSO claim 1 , DMF claim 1 , pyridine claim 1 , ammonia claim 1 , acetone claim 1 , acetonitrile claim 1 , ethers claim 1 , phosphines claim 1 , and combinations thereof.5. The compound of claim 4 , wherein the compound has a core comprising coordination sites claim 4 , and the coordinating molecules stabilize the compound by binding to the coordination sites.6. The compound of claim 5 , wherein one or more of the coordinating molecules is substituted by one or more of a pharmaceutical agent claim 5 , a fluorophore claim 5 , or a carbohydrate claim 5 , covalently bonded through a sulfur linkage at a coordination site.7. The compound of claim 1 , wherein the compound comprises a Agcore and a protecting layer of AgScapping structures.8. A silver cluster molecule comprising: a 32-silver-atom dodecahedral core consisting of a 12-silver-atom icosahedron encapsulated by a 20-silver-atom dodecahedron; and 30 coordinating ligands.9. The silver cluster molecule of claim 8 , wherein the coordinating ligands comprise p-MBA.10. The silver cluster molecule of claim 8 , wherein the dodecahedral core comprises icosahedral symmetry.11. The silver cluster molecule ...

NOVEL, HEAVY VITAMIN B12 DERIVATIVES

The invention discussed in this application relates to vitamin B12-based compounds that are useful as quantitative standards, particularly for the assessment of vitamin B12 deficiency. 1. A heavy vitamin B12 derivative having a mass shift of at least +7 over unlabelled vitamin B12 , wherein the heavy vitamin B12 derivative includes seven C atoms and the seven C atoms are located in the dimethylbenzimidazole moiety of the vitamin.24-. (canceled)5. The heavy vitamin B12 derivative of claim 1 , wherein the heavy vitamin B12 derivative has a mass shift of from +7 to +10 over unlabelled vitamin B12.6. The heavy vitamin B12 derivative of claim 5 , wherein the heavy vitamin B12 derivative has a mass shift of +7 over unlabelled vitamin B12.7. The heavy vitamin B12 derivative of claim 5 , wherein the heavy vitamin B12 derivative has a mass shift of +9 over unlabelled vitamin B12.10. The heavy vitamin B12 derivative of claim 1 , wherein the heavy vitamin B12 derivative further includes one or more H atoms.11. The heavy vitamin B12 derivative of claim 10 , wherein the heavy vitamin B12 derivative further includes two H atoms.12. A process for preparing a heavy vitamin B12 derivative according to claim 1 , the process including:{'sup': 13', '13, 'providing C-labelled 5,6-dimethylbenzimidazole having seven C atoms,'}providing cobinamide dicyanide,{'sup': '13', 'contacting the C-labelled 5,6-dimethylbenzimidazole with the cobinamide dicyanide in the presence of a bacterium,'}thereby producing the heavy vitamin B12 derivative.13. The process of claim 12 , wherein the C-labelled 5 claim 12 ,6-dimethylbenzimidazole has nine C atoms.14. The process of claim 12 , wherein the C-labelled 5 claim 12 ,6-dimethylbenzimidazole has one or more H atoms.15. The process of claim 14 , wherein the C-labelled 5 claim 14 ,6-dimethylbenzimidazole has two H atoms.16Salmonella entericaS. enterica. The process of claim 12 , wherein the bacterium is ().1718-. (canceled)19. The process of claim 12 , ...

FLUORINE-CONTAINING WATER SOLUBLE PLATINUM COMPLEXES FOR TUMOR TREATMENT AND PROCESS OF PREPARING SAME

Disclosed are fluorine-containing highly water-soluble platinum complexes for tumor treatment and preparation method, said platinum complexes being shown as formula (I); The present fluorine-containing platinum complexes exhibiting superior cytotoxicity and efficacy compare to the clinical drug oxaliplatin, the design strategy of the present platinum complexes is to enhance the solubility and stability favor its clinical use. 110-. (canceled)14. The method of claim 13 , wherein each M is Hydrogen claim 13 , Sodium or M together represents Barium;15. The method of claim 13 , wherein the inorganic base is NaOH claim 13 , KOH claim 13 , LiOH claim 13 , Ba(OH)2 or Cs(OH)2. The present invention relates to a water-soluble platinum complex, and especially relates to a fluorine-containing water-soluble platinum complex for tumor treatment and a process of preparing the same.Platinum antitumor drugs are the representative type of the drugs in the field of tumor treatment. They belong to the cell cycle non-specific agents, and the spectrum of antitumor efficacy of them includes sarcoma, malignant epithelial tumor, lymphoma and germ cell tumor. Currently, the world widely used representative platinum anticancer agents in clinic are cisplatin, carboplatin and oxaliplatin.The fatal weaknesses of platinum anticancer agents are strong toxic side effects and inherent and subsequently acquired resistance. In addition, as these drugs are organometallic compounds, the ubiquitous problem of all listed platinum drugs is the very low water solubility. The following table is the water-soluble data of three above-mentioned clinical drugs:The low water solubility brings a lot of adverse effects to the stability of pharmaceutical formulation and clinical applications, for example, it is difficult to successfully formulate them as convenient clinical preparations with an appropriate concentration. Moreover, the low water solubility also directly affects the accumulation and metabolism of the ...

IRON COMPLEX COMPOUNDS FOR THERAPUTIC USE

The present invention relates to iron complex compounds for therapeutic use which are low in arsenic, chromium, lead, cadmium, mercury and/or aluminum, compositions thereof and processes for preparing said iron complex compounds. 115-. (canceled)16. A process for preparing an iron carbohydrate complex compound comprising the steps of a. decomposing iron pentacarbonyl;', 'b. recrystallization of an iron salt from an aqueous solution thereof', 'c. extracting an aqueous iron salt solution with an organic solvent and recovering the iron salt by stripping the organic solvent;', 'd. precipitation at an anode during electrolysis of an aqueous iron salt solution;', 'e. contacting an aqueous iron salt solution with a base so as to form a precipitate of iron hydroxide and separating the precipitate from the liquid by filtration or centrifugation; or', 'f. distillation of ferric chloride from a mixture comprising ferric chloride and non-volatile impurities, wherein, '(i) obtaining an iron preparation by'}the iron preparation comprises iron in a form selected from a water-soluble iron salt, an iron hydroxide or an iron oxide-hydroxide,the amount of arsenic in the iron preparation does not exceed 4.5 μg per g of iron, andthe amount of lead in the iron preparation does not exceed 1.5 μg per g of iron; and(ii) reacting the iron preparation with a ligand in the presence of water so as to form the iron carbohydrate complex compound, and(iii) recovering said iron carbohydrate complex compound.17. The process of claim 16 , wherein recrystallization in step (i)(b) is recrystallization of ferric nitrate from an aqueous solution containing nitric acid.18. The process of claim 16 , wherein the aqueous iron salt solution of step (i)(c) is obtained during the processing of an iron-containing nickel ore.19. The process of claim 16 , wherein the organic solvent is an alcohol having about 4-20 carbon atoms or an organic solutions of an amine salt.20. The process of claim 16 , wherein the ...

ASYMMETRIC AUXILIARY GROUP

To provide a chiral reagent or a salt thereof. 3. The chiral reagent or a salt thereof in accordance with claim 2 , wherein each of Gand Gis a group of formula (II) claim 2 , wherein Gto Gare independently a hydrogen atom claim 2 , a nitro group claim 2 , a halogen atom claim 2 , a cyano group or Calkyl group.4. The chiral reagent or a salt thereof in accordance with claim 2 , wherein each of Gand Gis a group of formula (II) claim 2 , wherein each of Gto Gis a hydrogen atom.5. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (II) claim 2 , wherein Gto Gare independently a hydrogen atom claim 2 , a nitro group claim 2 , a halogen atom claim 2 , a cyano group or Calkyl group.6. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and Gis a group of formula (II) claim 2 , wherein each of Gand Gis a hydrogen atom and Gis a nitro group.7. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , Caryl group claim 2 , Caralkyl group claim 2 , Calkyl Caryl group claim 2 , Calkoxy Caryl group claim 2 , or Caryl Calkyl group.8. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , Caryl group claim 2 , Caralkyl group claim 2 , Calkyl Caryl group claim 2 , Calkoxy Caryl group claim 2 , or Caryl Calkyl group.9. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , or Caryl group.10. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and Gis a group of formula (III) claim 2 , wherein Gto Gare ...

Oligonucleotide and nucleic acid synthesis

The present invention relates to methods for the high fidelity synthesis of oligonucleotides and polynucleotides on a solid surface. In particular, the invention relates to methods of synthesising oligonucleotides, polynucleotides, and doublestranded polynucleotides/nucleic acids, such as DNA and XNA, wherein the process comprises thermally controlled deprotection steps at the 5′-OH of previously coupled nucleosides or nucleotides at selected sites on the surface of the substrate.

WATER SOLUBLE PLATINUM COMPLEXES FOR TUMOR TREATMENT AND PROCESS OF PREPARING SAME

Disclosed are water-soluble platinum complexes for tumor treatment and preparation method, said platinum complexes being shown as formula (I); The present platinum complexes exhibiting superior cytotoxicity and efficacy compare to the clinical drug oxaliplatin, the design strategy of the present platinum complexes is to enhance the solubility and stability favor its clinical use. 110-. (canceled)14. The method of claim 13 , wherein each M is Hydrogen claim 13 , Sodium or M together represents Barium;15. The method of claim 13 , wherein the inorganic base is NaOH claim 13 , KOH claim 13 , LiOH claim 13 , Ba(OH)2 or Cs(OH)2. The present invention relates to a water-soluble platinum complex, and especially relates to a water-soluble platinum complex for tumor treatment and a process of preparing the same.Platinum antitumor drugs are the representative type of the drugs in the field of tumor treatment. They belong to the cell cycle non-specific agents, and the spectrum of antitumor efficacy of them includes sarcoma, malignant epithelial tumor, lymphoma and germ cell tumor. Currently, the world widely used representative platinum anticancer agents in clinic are cisplatin, carboplatin and oxaliplatin.The fatal weaknesses of platinum anticancer agents are strong toxic side effects and inherent and subsequently acquired resistance. In addition, as these drugs are organometallic compounds, the ubiquitous problem of all listed platinum drugs is the very low water solubility. The following table is the water-soluble data of three above-mentioned clinical drugs:The low water solubility brings a lot of adverse effects to the stability of pharmaceutical formulation and clinical applications, for example, it is difficult to successfully formulate them as convenient clinical preparations with an appropriate concentration. Moreover, the low water solubility also directly affects the accumulation and metabolism of the drugs in the body. The metal containing platinum compounds are ...

METHOD FOR PREPARING PRECURSOR OF GENE EXPRESSION PROBE

A method for preparing a precursor of gene expression probe is revealed. First prepare 2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl bromide and 2,4-bis-O-(trimethylsilyl)-5-bromouracil respectively. Then use 2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl bromide and 2,4-bis-O-(trimethylsilyl)-5-bromouracil to perform a coupling reaction and get a 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromouracil. Next use 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromouracil generated and hexabutylditin to perform a substitution reaction in an anhydrous 1,4-dioxane solution and get 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-tributylstannyl)uracil. At last carry out debenzoylation of 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-tributylstannyl)uracil to get 5-tributylstannyl-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil (FSAU), a precursor of gene expression probe. 1. A method for preparing a precursor of gene expression probe comprising the steps of:carrying out bromination of 2-deoxy-2-fluoro-1,3,5-tri-O-benzoyl-α-D-arabinofurance in a hydrobromic acid in acetic acid solution to get 2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl bromide;also taking 5-bromouracil (5-BU) and hexamethyldisilazane (HMDS) to perform silylation protection and get 2,4-bis-O-(trimethylsilyl)-5-bromouracil;performing a coupling reaction of 2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl bromide with 2,4-bis-O-(trimethylsilyl)-5-bromouracil to get 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromouracil;performing a substitution reaction between 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromouracil and hexabutylditin in an anhydrous 1,4-dioxane solution to get 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-tributylstannyl)uracil; andcarrying out debenzoylation of 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-tributylstannyl)uracil to ...

PHOSPHOROAMIDATE ESTERS, AND USE AND SYNTHESIS THEREOF

Phosphoramidate esters and related nucleotide analogs useful in polynucleotide sequencing techniques, and synthetic methods for preparing those compounds, are disclosed. These compounds include nucleotide phosphoramidates analogs that are modified on the alpha-phosphate to enable attachment of a variety of application-specific substituents such as tether molecules. 2. The compound of wherein each of Rand Ris selected from an alkyl group and an oxyalkyl group claim 1 , either of which terminates in a functional group selected from carbon-carbon double bond claim 1 , carbon-carbon triple bond claim 1 , hydroxyl claim 1 , amine claim 1 , azide claim 1 , hydrazine claim 1 , thiol claim 1 , carboxyl claim 1 , formyl claim 1 , hydroxylamino and halogen.3. The compound of wherein each of Rand Ris selected from an alkyl group and an oxyalkyl group claim 1 , either of which terminates in a linker group (LG1) claim 1 , the LG1 bonded to a tether (T).4. The compound of wherein LG1 and LG2 are triazole groups.5. The compound of wherein Ris —(CH)—C≡CH and q is an integer selected from 2-10.9. The compound of wherein Ris —C≡C—(CH)—C≡CH.13. The compound of wherein each of LG1 and LG2 is a triazole group.18. The process of further comprising reacting the N-phosphoroamidate-monoester triphosphate (160) with a tether precursor of the formula X-T-X where X represents a reactive functional group that is reactive with the terminating functional group of Rand R claim 17 , so as to form linker groups LG1 and LG2.19. The process of wherein X is an azide group and the terminating functional groups of Rand Rare alkyne groups. The present invention is in the field of phosphoroamidate ester compounds, synthetic methods for making said compounds, and methods for the determination of nucleic acids using said compounds, e.g., in the field of single molecule sequencing.Chemically modified nucleotides have been extensively used in the study of many complicated biological systems. In particular, ...

METHOD OF DETECTING PEROXYNITRITE USING A COMPLEX OF A SACCHARIDE AND AN ARYLBORONATE-BASED FLUORESCENT PROBE

A method of detecting peroxynitrite in a sample is described comprising the steps of: (a) providing a complex of a saccharide with an aryl boronate compound of formula (I): Fp-L-Z-L-Ar—B(OH)(I) wherein: Fp comprises a fluorophore; Land Lare linker groups; Z is a fluorescence switch; and Ar is optionally substituted aryl; (b) contacting said aryl boronate-saccharide complex with said sample, whereby peroxynitrite in said sample cleaves said aryl boronate-saccharide complex to produce a compound of formula (II): F-L-Z-L-Ar—OH (II); and (c) detecting a decrease in a fluorescence intensity of said fluorophore resulting from said cleavage reaction in step (b). Peroxynitrite reacts quantitatively, rapidly, and selectively in step (b) of the reaction, whereby medical conditions associated with elevated peroxynitrite can be diagnosed. Also provided are compounds of formula (I) for use in the methods. 1. A method of detecting peroxynitrite in a sample comprising the steps of: {'br': None, 'sup': 1', '2, 'sub': '2', 'Fp-L-Z-L-Ar—B(OH)\u2003\u2003(I)'}, '(a) providing a complex of a saccharide with an aryl boronate compound of formula (I)wherein:Fp comprises a fluorophore;{'sup': 1', '2, 'Land Lare linker groups;'}Z is a fluorescence switch group; andAr is optionally substituted aryl; {'br': None, 'sup': 1', '2, 'Fp-L-Z-L-Ar—OH\u2003\u2003(II)'}, '(b) contacting said aryl boronate-saccharide complex with said sample, whereby peroxynitrite in said sample cleaves said boronate-saccharide complex to produce a compound of formula (II)and(c) detecting a decrease in a fluorescence intensity of said fluorophore resulting from said cleavage reaction in step (b).2. The method according to claim 1 , wherein the method comprises quantitating an amount of peroxynitrite in said sample by comparing said decrease in fluorescence intensity with decreases observed for reference amounts or concentrations of peroxynitrite.3. The method according to claim 1 , wherein said method is performed on a ...

REGIOSELECTIVE SILYL EXCHANGE OF PER-SILYLATED OLIGOSACCHARIDES

The present invention provides novel, regioselectively-acylated oligosaccharide compounds and methods for preparing them. In another aspect, the. invention provides a method for preparing a selectively-acylated oligosaccharide. The method includes forming a reaction mixture containing a protected oligosaccharide and an acylating agent. The protected oligosaccharide includes at least three hydroxyl moieties and each hydroxyl moiety is protected with a silyl protecting group. The reaction mixture is formed under conditions sufficient to selectively replace at least one silyl protecting group with a —C(0)-C1_6 alkyl group, and the selectively-acylated oligosaccharide comprises at least one —C(0)-C1_6 alkyl group and at least one silyl protecting group. 2. The compound according to claim 1 , wherein{'sup': 1', '2', '3', '4', '6', '7, 'R, R, R, R, and Rare each independently selected from the group consisting of —OR, the α-linked monosaccharide, and the β-linked monosaccharide;'}{'sup': 1a', '2a', '3a', '4a', '6a', '7, 'R, R, R, R, and Rare each independently selected from the group consisting of —ORand the linking moiety —O—;'}{'sup': 7', '8, 'sub': 1-6', '3, 'each Ris independently selected from the group consisting of —C(O)—Calkyl and —Si(R); and'}{'sup': 1', '2', '3', '4', '6', '1a', '2a', '3a', '4a', '6a', '7', '7', '8, 'sub': '3', 'at least one of R, R, R, R, R, R, R, R, R, and Ris —OR, wherein Ris —Si(R).'}3. The compound according to claim 2 , wherein Ris selected from the group consisting of the α-linked monosaccharide and the β-linked monosaccharide.4. The compound according to claim 3 , wherein one of R claim 3 , Rand Ris the linking moiety —O—.5. The compound according to claim 4 , wherein Ris —OR claim 4 , wherein Ris —C(O)—Calkyl.6. The compound according to claim 5 , wherein at least one of R claim 5 , R claim 5 , R claim 5 , R claim 5 , and Ris —OR claim 5 , wherein Ris —C(O)—Calkyl.7. (canceled)10. The compound according to claim 9 , wherein Ris —C(O)— ...

Intermediate for Production of Nucleoside Analog and Method for Producing the Same

A compound represented by the general formula (III) which serves as an intermediate of an oligonucleotide analog having stable and excellent antisense or antigene activity or having excellent activity as a detection reagent (probe) for a specific gene or as a primer for the initiation of amplification of a specific gene can be produced at high yields regardless of the type of nucleobase by a method comprising reacting a compound represented by the general formula (II) or a salt thereof with a trimethylsilylated compound obtained from a compound represented by the general formula (IVb), wherein X, Y, Z, A, R, and B are as defined in claim 2. The method of claim 1 , wherein X is a methyl group substituted by 1 to 3 aryl groups claim 1 , or a methyl group substituted by 1 to 3 aryl groups wherein the aryl ring is substituted by a lower alkyl claim 1 , lower alkoxy claim 1 , halogen claim 1 , or cyano group.3. The method of claim 1 , wherein X is a benzyl group claim 1 , a p-methoxybenzyl group claim 1 , a dimethoxytrityl group claim 1 , or a monomethoxytrityl group.4. The method of claim 1 , wherein Y is a methyl group substituted by 1 to 3 aryl groups claim 1 , or a methyl group substituted by 1 to 3 aryl groups wherein the aryl ring is substituted by a lower alkyl claim 1 , lower alkoxy claim 1 , halogen claim 1 , or cyano group.5. The method of claim 1 , wherein Y is a benzyl group claim 1 , a β-naphthylmethyl group claim 1 , or a p-methoxybenzyl group.6. The method of claim 1 , wherein Z is an aliphatic acyl group having 2 to 4 carbon atoms.7. The method of claim 1 , wherein Z is an acetyl group.8. The method of claim 1 , wherein A is a methylene group or an ethylene group.9. The method of claim 1 , wherein A is a methylene group.10. The method of claim 1 , wherein B is a 6-aminopurin-9-yl group claim 1 , a 6-aminopurin-9-yl group with the amino group protected claim 1 , a 2 claim 1 ,6-diaminopurin-9-yl group claim 1 , a 2-amino-6-chloropurin-9-yl group claim 1 , a ...

BORON-CONTAINING SMALL MOLECULES

This invention relates to compounds useful for treating fungal infections, more specifically topical treatment of onychomycosis and/or cutaneous fungal infections. This invention is directed to compounds that are active against fungi and have properties that allow the compound, when placed in contact with a patient, to reach the particular part of the skin, nail, hair, claw or hoof infected by the fungus. In particular the present compounds have physiochemical properties that facilitate penetration of the nail plate. 9. The pharmaceutical formulation of claim 6 , wherein Ris a member selected from a negative charge claim 6 , H and a salt counterion.10. The pharmaceutical formulation of claim 9 , wherein Rand Rare H.11. The pharmaceutical formulation of claim 6 , wherein one member selected from Rand Ris H and the other member selected from Rand Ris a member selected from halo claim 6 , methyl claim 6 , cyano claim 6 , methoxy claim 6 , hydroxymethyl and p-cyanophenyloxy.12. The pharmaceutical formulation of claim 6 , wherein Rand Rare members independently selected from fluoro claim 6 , chloro claim 6 , methyl claim 6 , cyano claim 6 , methoxy claim 6 , hydroxymethyl claim 6 , and p-cyanophenyl.13. The pharmaceutical formulation of claim 6 , wherein Ris a member selected from a negative charge claim 6 , H and a salt counterion; Ris H; Ris F and Ris H.14. The pharmaceutical formulation of claim 6 , wherein Ris a member selected from a negative charge claim 6 , H and a salt counterion; Ris H; Ris 4-cyanophenoxy and Ris H.15. The pharmaceutical formulation of claim 4 , wherein Rand R claim 4 , along with the atoms to which they are attached claim 4 , are joined to form a phenyl group.17. The pharmaceutical formulation of claim 4 , wherein said excipient is a pharmaceutically acceptable topical carrier.18. The pharmaceutical formulation of claim 4 , wherein said compound is present in said pharmaceutical formulation in a concentration of from about 1% to about 10%.19. A ...

METHODS OF SYNTHESIZING LABELED NUCLEOSIDES

Disclosed herein, inter alia, are compounds, compositions, and methods of synthesizing labeled nucleosides. 2. The method of claim 1 , wherein the methylthiomethyl donor is dimethyl sulfoxide (DMSO).4. The method of claim 3 , wherein Ris substituted or unsubstituted alkyl.5. The method of claim 3 , wherein Ris substituted or unsubstituted C-Calkyl.6. The method of claim 3 , wherein Ris unsubstituted C-Calkyl.7. The method of claim 3 , wherein Ris methyl claim 3 , ethyl claim 3 , isopropyl claim 3 , n-propyl claim 3 , n-butyl claim 3 , sec-butyl claim 3 , isobutyl claim 3 , or tert-butyl.8. The method of claim 3 , wherein Ris tert-butyl.9. The method of claim 1 , wherein B is a protected nucleobase.10. The method of claim 1 , wherein B is a protected nucleobase substituted with a covalent linker to a reactive group.11. The method of claim 1 , wherein B is a substituted or unsubstituted cytosinyl claim 1 , substituted or unsubstituted guaninyl claim 1 , substituted or unsubstituted adeninyl claim 1 , substituted or unsubstituted thyminyl claim 1 , substituted or unsubstituted uracilyl claim 1 , substituted or unsubstituted hypoxanthinyl claim 1 , substituted or unsubstituted xanthinyl claim 1 , substituted or unsubstituted deaza-adeninyl claim 1 , substituted or unsubstituted deaza-guaninyl claim 1 , substituted or unsubstituted deaza-hypoxanthinyl claim 1 , substituted or unsubstituted 7-methylguaninyl claim 1 , substituted or unsubstituted 5 claim 1 ,6-dihydrouracilyl claim 1 , substituted or unsubstituted 5-methylcytosinyl claim 1 , or substituted or unsubstituted 5-hydroxymethylcytosinyl. This application claims the benefit of U.S. Provisional Application No. 62/558,181, filed Sep. 13, 2017, which is incorporated herein by reference in its entirety and for all purposes.DNA sequencing is a fundamental tool in biological and medical research, and is especially important for the paradigm of personalized medicine. Various new DNA sequencing methods have been ...

PROCESSES AND INTERMEDIATES FOR PREPARING ANTI-HIV AGENTS

The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties. 156-. (canceled)58. The method of claim 57 , wherein Bn is unsubstituted.59. The method of claim 57 , wherein the silylating agent is bis(trimethylsilyl)trifluoroacetamide claim 57 , chlorotrimethylsilane claim 57 , hexamethyldisiloxane claim 57 , hexamethyldisilazane claim 57 , trimethylsilyldiethylamine claim 57 , ethyl trimethylsilylacetate claim 57 , bis(trimethylsilyl)sulfate claim 57 , N claim 57 ,N-bitrimethylsilylurea claim 57 , trimethylsilylimidazole or trimethylsilyl trifluoromethanesulfonate.60. The method of claim 57 , wherein the alkylating agent is benzyl chloromethyl ether or R′—CH—O-Bn wherein R′ is Br claim 57 , I claim 57 , OTs claim 57 , OTf or OMs.61. The method of claim 57 , wherein the hydrolyzing agent is a metal hydroxide.62. The method of claim 61 , wherein the metal hydroxide is potassium hydroxide.63. The method of claim 57 , wherein the acid is hydrochloric acid. This patent application claims the benefit of priority of U.S. application Ser. No. 61/488,133 filed May 19, 2011, which application is hereby incorporated by reference.International Patent Application Publication Number WO 2006/110157 and International Patent Application Publication Number WO 2006/015261 provide phosphohamidate derivatives of(2R′,5R′)-9-(3-fluoro-2,5-dihydro-5-phosphonomethoxy-2-furanyl)adenine that are reported to be useful as anti-HIV agents. Compound 13 is one such derivative.International Patent Application Publication Number WO 2010/005986 provides salt forms of compound 13 including the citrate salt (compound 14) which arc also reported to be useful as anti-HIV agents.There is currently a need for improved methods for preparing certain compounds reported in International Patent Application Publication Numbers WO 2006/110157, WO 2006/015261 and WO 2010/005986. In particular, there is a need for new synthetic ...

DUPLEX-SELECTIVE ORGANOMETALLIC DNA INTERCALATORS

Disclosed herein are organometallic complexes and methods of using the same in detecting double stranded DNA or RNA, selectively over single stranded DNA or RNA. 6. The organometallic complex of any one of to , wherein at least one Het is phenanthrolinyl.7. The organometallic complex of any one of to , wherein R is null (i.e. , Het is substituted with CalkylCO) , H , or Calkyl.8. The organometallic complex of any one of to , wherein at least one Het is substituted with a Calkylene-COR , and R comprises an oligonucleotide moiety.9. An organometallic complex having a structure selected from Complexes 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , and 10 , preferably Complex 3 , 5 , 6 , 8 , or 9.10. The organometallic complex of any one of to , being neutral.11. The organometallic complex of any one of to , having a +1 or +2 charge.12. The organometallic complex of any one of to , wherein n is 0.13. The organometallic complex of any one of to , wherein M is Ru.14. The organometallic complex of any one of to , wherein M is Os.15. The organometallic complex of any one of to , further comprising a chloride or hexafluorophosphate counter anion.16. The organometallic complex of any one of to , further comprising a sodium counter cation.17. A conjugate comprising the organometallic complex of any one of to and an oligonucleotide , wherein the organometallic complex comprises at least one R comprising an oligonucleotide moiety.18. A nanoparticle comprising a plurality of cross-linked oligonucleotides and at least one conjugate of , or at least one complex as disclosed in any one of to .19. A method of determining the presence or concentration of a target molecule in a sample comprising contacting the sample with a complex of any one of to under conditions that allow association of the target molecule with the complex , wherein upon association of the target molecule and the complex , the complex undergoes a detectable change , said change indicative of the presence of the target ...

COBALAMIN DERIVATIVES AND THEIR USE FOR THE TREATMENT OF DISEASES CAUSED BY LACK OF VITAMIN B12 SUPPLY

The present invention concerns cobalamin derivatives of formula (I) 3. A pharmaceutical composition comprising a cobalamin derivative according to as active pharmaceutical ingredient (API).4. The pharmaceutical composition according to in the form of an orally applicable formulation.5. The pharmaceutical composition according to in the form of a parenterally applicable formulation.6. A food supplement comprising a cobalamin derivative according to and a suitable additive.8. A method of treating a B-related disease comprising the step of administering to a subject in need thereof the cobalamin derivative according to .9. The method according to claim 8 , wherein the B-related disease being treated is caused by an impairment of cblC.10. The method according to claim 8 , wherein the B-related disease being treated is age-related mental degeneration.11. The method according to claim 10 , wherein the age-related mental degeneration being treated is dementia.12. The method according to claim 10 , wherein the age-related mental degeneration being treated is Alzheimer's disease.13. The process according to claim 7 , wherein Z is a halogen atom. This application corresponds to the U.S. National phase of International Application No. PCT/EP2018/063597, filed May 24, 2018, which, in turn, claims priority to European Patent Application No. 17.172613.6 filed May 24, 2017, the contents of which are incorporated by reference herein in their entirety.Mammals utilize Bor cobalamin derivatives as co-factors for two enzymes, namely methionine synthase and methylmalonyl-CoA mutase. Methionine synthase catalyzes the methylation of homocysteine to form the amino acid methionine concomitantly with the regeneration of tetrahydrofolate from 5-methyltetrahydrofolate. This reaction is strictly dependent on methylcobalamin (MeCbl). Tetrahydrofolate is required to support the biosynthesis of purines and pyrimidines and therefore it is essential for cellular proliferation and homeostasis. ...

METHODS AND COMPOSITIONS FOR ADMINISTRATION OF IRON

The present invention generally relates to treatment of iron-related conditions with iron carbohydrate complexes. One aspect of the invention is a method of treatment of iron-related conditions with a single unit dosage of at least about 0.6 grams of elemental iron via an iron carbohydrate complex. The method generally employs iron carbohydrate complexes with nearly neutral pH, physiological osmolarity, and stable and non-immunogenic carbohydrate components so as to rapidly administer high single unit doses of iron intravenously to patients in need thereof. 1. A method of treating a disease , disorder , or condition characterized by iron deficiency or dysfunctional iron metabolism resulting in reduced bioavailability of dietary iron , comprising administering to a subject in need thereof an iron carbohydrate complex in a single dosage of at least 9 mg of elemental iron per kg of body weight , wherein:a) the iron carbohydrate complex is substantially non-immunogenic, and has substantially no cross reactivity with anti-dextran antibodies; andb) the iron carbohydrate complex is an iron polyisomaltose complex or an iron polyglucose sorbitol carboxymethyl ether complex.2. The method of claim 1 , wherein the iron carbohydrate complex is an iron polyisomaltose complex.3. The method of claim 2 , wherein the polyisomaltose is reduced polyisomaltose.4. The method of claim 1 , wherein the iron carbohydrate complex is an iron polyglucose sorbitol carboxymethyl ether complex.5. The method of claim 4 , wherein the iron carbohydrate complex is a polyglucose sorbitol carboxymethyl ether-coated non-stoichiometric magnetite complex.6. The method of claim 4 , wherein the iron carbohydrate complex has a crystal size of 6.2 to 7.3 nm.7. The method of claim 5 , wherein the iron carbohydrate complex has a crystal size of 6.2 to 7.3 nm.8. The method of claim 4 , wherein the iron carbohydrate complex has an average colloidal particle size of about 30 nm.9. The method of claim 5 , wherein ...

MODIFIED NUCLEOSIDE AND SYNTHETIC METHODS THEREOF

Disclosed are a modified cytidine compound, i.e. a new derivative cytidine generated by adding a guanidyl at position 4 of a cytidine, and a nucleic acid containing the modified compound, for example, RNA. The nucleic acid containing the modified cytidine, especially mRNA, can significantly increase the expression quantity of the mRNA in vivo.

COMPOSITIONS, KITS, AND METHODS TO INDUCE ACQUIRED CYTORESISTANCE USING STRESS PROTEIN INDUCERS

The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism. 1. A method of protecting an organ of a human patient from injury based on a scheduled insult comprising administering to the organ a therapeutically effective amount of (i) iron sucrose; and (ii) vitamin B12 or a derivative thereof , the therapeutically effective amount being administered before the insult to the organ occurs.2. The method of claim 1 , wherein the insult is a scheduled insult.3. The method of claim 2 , wherein the scheduled insult is surgery claim 2 , chemotherapy claim 2 , or radiocontrast toxicity.4. The method of claim 3 , wherein the surgery is an organ transplant surgery.5. The method of claim 2 , wherein the administration occurs at least 2 hours before the scheduled insult to the organ occurs.6. The method of claim 2 , wherein the administration occurs at least 4 hours before the scheduled insult to the organ occurs.7. The method of claim 2 , wherein the administration occurs at least 12 hours before the scheduled insult to the organ occurs.8. The method of claim 2 , wherein the administration occurs at least 18 hours before the scheduled insult to the organ occurs.9. The method of claim 1 , wherein the organ is a transplanted organ.10. The method of claim 1 , wherein the organ is a heart claim 1 , kidney claim 1 , liver claim 1 , or lung.11. The method of claim 1 , wherein the organ is a kidney and protection is evidenced by prevention or reduction in BUN or serum creatinine increases as compared to a reference level.12. A method of protecting an organ of a human patient from injury based on a scheduled insult comprising administering to the organ a therapeutically effective amount of (i) iron sucrose; and (ii) vitamin B12 or a derivative thereof ...

MULTIVALENT SACCHARIDE COMPLEX, RADIOACTIVE MULTIVALENT SACCHARIDE COMPLEX CONTRAST AGENT, AND USE THEREOF

Disclosed herein are a multivalent saccharide complex, a radioactive multivalent saccharide complex contrast agent and use thereof. The multivalent saccharide complex has a chelator, a linker, and glucose, and is configured to diagnose and evaluate the therapeutic effect of cancers. 1. A multivalent saccharide complex , comprising:a chelator, which is 1,4,7-triazacyclononane-N,N′,N′″-triacetic acid (NOTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), di ethyl enetriaminepentaacetic acid (DTPA), 1,4,8,11-tetraazacyclotetradecane-N,N′,N″,N′″-tetraacetic acid (TETA), or 1,4,7-triazacyclononane phosphinic acid (TRAP);at least two molecules of a linker, one end of which is attached to the chelator, wherein the linker is polyethylene glycol (PEG), an amino acid, or a peptide; andat least two molecules of glucose, attached respectively the other end of the linker.3. The multivalent saccharide complex according to claim 1 , wherein R1 claim 1 , R2 and R3 are all glucose.4. The multivalent saccharide complex according to claim 1 , further comprising a radioactive isotope labeled on the compound of Formula (1).5. The multivalent saccharide complex according to claim 4 , wherein the radioactive isotope is rhenium-188 claim 4 , technetium-99 m claim 4 , indium-111 claim 4 , lutetium-177 claim 4 , gallium-68 claim 4 , yttrium 90 claim 4 , flurine-18 claim 4 , or copper-64.6. The multivalent saccharide complex according to claim 4 , wherein the radioactive isotope is gallium-68.7. A contrast agent claim 4 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a multivalent saccharide complex according to ; and'}an excipient acceptable in the contrast agent.8. A method for diagnosing cancers claim 4 , comprising administering an effective amount of a multivalent saccharide complex according to to a subject.9. The use according to claim 8 , wherein the cancers are selected from the group consisting of lymphoma claim 8 , multiple myeloma claim 8 , ...

Development of Imaging and Therapeutic Glucose Analogues for Sodium Dependent Glucose Transporters

The present disclosure describes glucose analogs that are transported on the sodium dependent glucose transporters (SGLTs). These compounds may be useful in a variety of disorders such as, for example, cancer, heart disease, neurological disorders, diabetes, and atherosclerosis. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The compound of claim 1 , wherein Q is —O— claim 1 , Z is a fluorophore claim 1 , and at least two of R claim 1 , R claim 1 , R claim 1 , and Rare not hydrogen.3. The compound of claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , and Ris hydrogen.4. The compound of claim 1 , wherein Z is a radiolabel claim 1 , a radioisotope claim 1 , or a radiotherapeutic.5. The compound of claim 1 , wherein Z is a radiolabel.6. The compound of claim 5 , wherein the radiolabel comprises a ligand and a metal.7. The compound of claim 6 , wherein the ligand is selected from DOTA claim 6 , NOTA claim 6 , DFO claim 6 , and DOTA-DBCO.8. The compound of claim 6 , wherein the metal is selected from Ga claim 6 , Cu claim 6 , Lu claim 6 , Zr claim 6 , Y claim 6 , Y claim 6 , Sc claim 6 , Sc claim 6 , Tb claim 6 , Rb claim 6 , Ac claim 6 , At claim 6 , Th claim 6 , Bi claim 6 , Ra claim 6 , Ra claim 6 , Sr claim 6 , and Sm.9. The compound of claim 1 , wherein Z is a radioisotope selected from F claim 1 , I claim 1 , and I.14. The compound of claim 13 , wherein the radioisotope is selected from Ga claim 13 , Cu claim 13 , Lu claim 13 , Zr claim 13 , Y claim 13 , Y claim 13 , Sc claim 13 , Sc claim 13 , Tb claim 13 , Rb claim 13 , Ac claim 13 , At claim 13 , Th claim 13 , Bi claim 13 , Ra claim 13 , Ra claim 13 , Sr claim 13 , and Sm.15. A method for the treatment of a disorder in a subject claim 1 , the method comprising administering to the subject an effective amount of at least one compound of claim 1 , wherein the disorder is a disorder of ...

HCV POLYMERASE INHIBITORS

The invention provides compounds of the formula: 3. The compound according to claim 2 , wherein Ris NH.5. The compound according to claim 4 , wherein Ris H.7. (canceled)8. The compound according to claim 1 ,wherein U is O.916.-. (canceled)17. The compound according to claim 1 , wherein Ris H.18. The compound according to claim 17 , wherein{'sup': 15', '15′, 'sub': 1', '6, 'both Rare H or C-Calkyl, both R are H; and'}{'sup': '16', 'sub': 1', '6', '3', '7, 'both Rare C-Calkyl or C-Ccycloalkyl.'}1938.-. (canceled)39. A pharmaceutical composition comprising a compound according to in association with a pharmaceutically acceptable adjuvant claim 1 , diluent or carrier.40. A pharmaceutical composition comprising a compound according to claim 1 , further comprising one or more additional other antiviral agent(s).41. A method for the treatment of hepatitis C virus infection comprising the administration of a compound according to .42. (canceled)43. The compound according to claim 18 , wherein both Rare ethyl claim 18 , n-propyl claim 18 , isopropyl claim 18 , n-butyl or isobutyl claim 18 , both R are H claim 18 , and both Rare methyl claim 18 , ethyl claim 18 , isopropyl claim 18 , cyclopropyl claim 18 , cyclobutyl or cyclopentyl.44. The compound according to claim 43 , wherein both Rare C-Calkyl or C-Ccycloalkyl.45. The compound according to claim 44 , wherein both Rare methyl claim 44 , ethyl claim 44 , propyl or isopropyl.46. The compound according to claim 45 , wherein both Rare isopropyl. This Nonprovisional application is a Continuation application of co-pending application Ser. No. 15/360,360 filed on Nov. 23, 2016, which is a Continuation of application Ser. No. 15/210,500 filed on Jul. 14, 2016, now U.S. Pat. No. 9,540,411, which is a Continuation of application Ser. No. 14/634,449 filed on Feb. 27, 2015, which is a Continuation-In-Part application of PCT International Application No. PCT/SE2014/051005 filed on Sep. 2, 2014, which claims priority under 35 U.S. C. § ...

HCV POLYMERASE INHIBITORS

The invention provides compounds of the formula: 142.-. (canceled)45. The process of claim 44 , wherein Pgand Pgboth are triisopropylsilyl or benzoyl.46. The process of claim 45 , wherein Pgand Pgboth are triisopropylsilyl.47. The process of claim 44 , wherein Lg is methylsulfonate.48. The process of claim 44 , wherein the reaction of compound 1e with uracil in step f is performed in the presence of hexamethyldisilazane and a Lewis acid.49. The process of claim 48 , wherein the Lewis acid is TMS triflate.50. The process of claim 44 , wherein removal the hydroxy protecting groups in step g is performed by treatment with an acid in an aqueous solution.51. The process of claim 44 , wherein removal the hydroxy protecting groups is performed by treatment with aqueous acetic acid. This Nonprovisional application is a Continuation-In-Part application of PCT International Application No. PCT/SE2014/051005 filed on Sep. 2, 2014, which claims priority under 35 U.S. C. §119 on Patent Application No. 1352026-8 filed in Sweden on Sep. 4, 2013, on Patent Application No. 1351169-6 filed in Sweden on Oct. 3, 2013, and on Patent Application No, 1450152-2 filed in Sweden on Feb. 12, 2014, the entire contents of each of which are hereby incorporated by reference.The present invention relates to nucleoside derivatives which are inhibitors of the polymerase of hepatitis C virus (HCV). The invention further relates to prodrugs of the nucleoside derivatives, compositions comprising them, and methods for their use in the treatment or prophylaxis of HCV infection.HCV is a single stranded, positive-sense RNA virus belonging to the Flaviviridae family of viruses in the hepacivirus genus. The NS5B region of the RNA polygene encodes an RNA dependent RNA polymerase (RdRp), which is essential to viral replication. Following the initial acute infection, a majority of infected individuals develop chronic hepatitis because HCV replicates preferentially in hepatocytes but is not directly cytopathic. ...

UBA5 INHIBITORS

The present disclosure relates to compounds of the Formula (I), which are UBA5 inhibitors. 4. (canceled)5. The compound of the Formula (I) according to claim 1 , wherein L is (C-C)-alkylene or (C-C)-alkenylene claim 1 , wherein (i) one to five carbon atoms are optionally replaced with a heteroatom selected from O claim 1 , NR′ and S claim 1 , wherein R′ is H claim 1 , (C-C)-alkyl or —C(═O)—(C-C)-alkyl; (ii) two or three adjacent carbon atoms are joined together to form a (C-C)-cycloalkyl group or —(C)-aryl group; and/or (iii) the (C-C)-alkylene or (C-C)-alkenylene is optionally substituted with at least one fluoro.6. (canceled)7. The compound of the Formula (I) according to claim 5 , wherein L is (C-C)-alkylene or (C-C)-alkenylene.8. (canceled)9. (canceled)10. (canceled)11. The compound of the Formula (I) according to claim 1 , wherein W is —NH—C(═O)—.12. The compound of the Formula (I) according to claim 1 , wherein W is —NR′— claim 1 , wherein R′ is H claim 1 , (C-C)-alkyl or —C(═O)—(C-C)-alkyl.13. (canceled)14. (canceled)15. (canceled)16. (canceled)19. (canceled)20. The compound of the Formula (I) according claim 1 , wherein Rand Rare each independently or simultaneously(i) H;(ii) cyclopentyl or cyclohexyl;(iii) morpholinyl or piperazinyl;{'sub': '2', '(iv) phenyl or —(CH)-phenyl;'}{'sub': '2', '(v) naphthyl or —(CH)-naphthyl;'}{'sub': '2', '(vi) pyridinyl or —CH-pyridinyl;'}or{'sub': 1', '2, 'Rand Rare joined together to form a'}(vii) guanine or a guanine derivative;(viii) cytosine or a cytosine derivative;(ix) thymine or a thymine derivative; or(x) adenine or an adenine derivative.21. (canceled)22. The compound of the Formula (I) according claim 20 , wherein Rand Rare joined together to form adenine or an adenine derivative.23. (canceled)25. The compound of the Formula (I) according to claim 1 , wherein M is Zn claim 1 , Cu claim 1 , Fe claim 1 , Ni claim 1 , Mn claim 1 , Co claim 1 , Pd claim 1 , Gd claim 1 , Tb claim 1 , Eu or Mo.26. The compound of the ...

COMPLEXES OF NUCLEIC ACID MOLECULES AND METALS

Provided is a conductive nucleic acid-metal complex including a polyG and PolyC consisting nucleic acids associated with a plurality of metal atoms, and methods for its preparation. 160.-. (canceled)61. A double-stranded nucleic acid-metal complex , comprising:a double stranded nucleic acid comprising at least one continuous region consisting guanine (G) and cytosine (C) nucleotides, anda plurality of metal atoms;wherein said at least one continuous region is associated with the plurality of said metal atoms.62. The complex of claim 61 , wherein within said continuous region one strand of the double strand nucleic acid consists essentially of G and the other strand consists essentially of C nucleotide bases claim 61 , or within said continuous region each of the two strands of the double stranded nucleic acid consists a combination of G and C nucleotides.63. The complex of claim 61 , wherein the nucleic acid part of the complex comprises a combination of two or more continuous regions claim 61 , wherein along at least one of said two or more continuous regions claim 61 , one strand consists essentially of G and the other consists essentially of C nucleotides claim 61 , and along at least one other of said two or more continuous regions claim 61 , each of the strands consists a combination of G and C nucleotides.64. The complex of claim 61 , wherein the double stranded nucleic acid strand is DNA claim 61 , RNA or a chimera of DNA and RNA.65. The complex of claim 61 , wherein the metal atom is a transition metal selected from Groups IIIB claim 61 , IVB claim 61 , VB claim 61 , VIB claim 61 , VIIB claim 61 , VIIIB claim 61 , IB and IIB of block d of the Periodic Table.66. The complex of claim 65 , wherein the metal is selected from Ag claim 65 , Cu claim 65 , Ni claim 65 , Zn claim 65 , Co claim 65 , Cr and Fe.67. The complex of claim 66 , wherein the metal is Ag.68. A double-stranded nucleic acid-metal complex claim 66 , comprising:a DNA or RNA or a chimeric DNA-RNA ...

Compounds linked with a saccharide metal complex and uses thereof

The present disclosure provides compounds linked with a saccharide-metal complex. The compounds are designed to protect organs by inducing acquired cytoresistance without causing injury to the organ, among other potential uses.

BORONIC ACID DERIVATIVES AND THERAPEUTIC USES THEREOF

Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents. Other embodiments relate to pharmaceutical compositions containing boronic acid derivatives and additional excipient such as meglumine. 3. The compound of or , wherein:{'sup': '4', 'sub': 1-4', '1-4, 'each Ris independently selected from the group consisting of —H, —Calkyl, —OH, —O—Calkyl, and halogen; and'}{'sub': 1-4', '1-4, 'Z is selected from the group consisting of aryl optionally substituted with Calkyl, amino, hydroxy, or halogen and heteroaryl optionally substituted with Calkyl, amino, hydroxy, or halogen.'}54. The compound of any one of - claims 1 , wherein R is H.64. The compound of any one of - claims 1 , wherein R is —CRROC(O)Calkyl or —CRROC(O)OCalkyl.7. The compound of claim 6 , where R is —CRROC(O)Calkyl or —CRROC(O)OCalkyl.8. The compound or claim 6 , wherein Rin R is H and Rin R is H or —CH.98. The compound of any one of - claims 1 , wherein Ris selected from H claims 1 , F claims 1 , Cl claims 1 , —CH claims 1 , —CF claims 1 , —OCH claims 1 , and —SCH.109. The compound of any one of - claims 1 , wherein G is H.119. The compound of any one of - claims 1 , wherein G is —NH.129. The compound of any one of - claims 1 , wherein G is —C(O)NRRand Rand Rin G are each independently selected from —H and Calkyl.13. The compound of claim 12 , wherein Rin G is —CHand Rin G is —CH.149. The compound of any one of - claims 1 , wherein G is —CHC(O)NRRand Rand Rin G are each independently selected from —H and Calkyl.15. The compound of claim 14 , wherein Rin G is —CHand Rin G is H or —CH.169. The compound of - claims 1 , wherein:{'sub': '2', 'G is —CH—Y—Z;'}Y is —S—; andZ is selected from the group consisting of imidazole, N-methylimidazole, aminoimidazole, triazole, N-methyltriazole, aminotriazole, tetrazole, N-methyltetrazole, aminotetrazole, thiazole, ...

METHODS AND INTERMEDIATES FOR THE PREPARATION OF FONDAPARINUX

The present invention relates to methods for the synthesis of fondaparinux and intermediates thereto. 233-. (canceled)35. (canceled)37118-. (canceled)120. The method of claim 119 , wherein Xis in the alpha configuration.121. The method of claim 119 , wherein Xis in the beta configuration.122. The method of claim 119 , wherein Xis Calkoxy.123. The method of claim 122 , wherein Xis methoxy.124. The method of claim 123 , wherein Xis alpha-methoxy.125. The method of claim 119 , wherein Xis O(protecting group).126. The method of claim 125 , wherein the protecting group is a silyl protecting group.127. The method of claim 126 , wherein Xis t-butyldiphenylsilyloxy.128. The method of claim 119 , wherein R claim 119 , R claim 119 , and Rare independently selected from the group consisting of N claim 119 , —NH(Cbz) claim 119 , —NH(Boc) claim 119 , —NH(Fmoc) claim 119 , —NHC(O)CCl claim 119 , —NHC(O)CH claim 119 , and —N(C(O)CH).129. The method of claim 119 , wherein R claim 119 , R claim 119 , and Rare the same.130. The method of claim 119 , wherein R claim 119 , R claim 119 , and Rare each a silyl protecting group.131. The method of claim 119 , wherein R claim 119 , R claim 119 , and Rare the same.132. The method of claim 131 , wherein R claim 131 , Rand Rare t-butyldiphenylsilyl.133. The method of wherein Rand Rare the same.134. The method of claim 119 , wherein Rand Rare each optionally substituted benzyl.135. The method of claim 134 , wherein Rand Rare p-bromobenzyl.136. The method of claim 119 , wherein R claim 119 , Rand Rare t-butyldiphenylsilyl; and Rand Rare p-bromobenzyl.137. The method of claim 119 , wherein Rand Rare the same.138. The method of claim 119 , wherein Rand Rare levulinyl.139. The method of claim 119 , wherein R claim 119 , Rand Rare t-butyldiphenylsilyl; and Rand Rare levulinyl.140. The method of claim 119 , wherein Ris —Si(R).141. The method of claim 140 , wherein Ris t-butyldiphenylsilyl.142. The method of claim 119 , wherein Ris C(O)R.143. The ...

COMPLEX COMPOUNDS OF GERMANIUM, METHODS FOR PRODUCING SAME, AND DRUGS

The invention relates to the development of drugs intended for the prophylaxis and/or treatment of viral diseases caused, in particular, by herpes viruses. What are proposed are complex compounds of germanium having the general structural formula: 1. Germanium complex compounds having the general structural formula (I):{'br': None, 'sub': x', 'y', 'z, 'Ge[AD][CA][AA]\u2003\u2003(I)'}wherein AD is a purine nitrogenous base derivative having an antiviral activity;CA is a hydroxycarboxylic acid;AA is an amino acid selected from α-amino acids,wherein x=1-2, y=2-4, and z=0-2, and whereinall ADs in the complex compound are the same or different,all CAs in the complex compound are the same or different, andall AAs in the complex compound are the same or different.2. The complex compounds according to claim 1 , wherein the AD is a derivative of guanine or adenine.3. The complex compounds according to claim 2 , wherein the guanine derivative is selected from the group consisting of acyclovir (9-[(2-hydroxyethoxy)methyl]guanine) claim 2 , valacyclovir (2-(guanin-9-ylmethoxy)ethyl L-valine ether) claim 2 , gancyclovir (9-[(1 claim 2 ,3-dihydroxy-2-propoxy)methyl]guanine) claim 2 , pencyclovir (9-[4-hydroxy-3-(hydroxymethyl)butyl]guanine) claim 2 , or mixtures thereof.4. The complex compounds according to claim 2 , wherein the adenine derivative is selected to be vidarabine (9-β-D-ribofuranosyl adenine).5. The complex compounds according to claim 1 , wherein the amino acid AA is selected from the group consisting of arginine claim 1 , glycine claim 1 , lysine claim 1 , threonine claim 1 , or mixtures thereof.6. The complex compounds according to claim 1 , wherein the hydroxycarboxylic acid CA is selected from the group consisting of citric acid claim 1 , lactic acid claim 1 , malic acid claim 1 , or mixtures thereof.7. A method for preparing germanium complex compounds according to claim 1 , comprising the steps of:(a) mixing germanium dioxide with water to provide an aqueous ...

NOVEL SPIROBICYCLIC INTERMEDIATES

The present invention relates to novel spirobicyclic intermediates useful in the synthesis of spirobicyclic nucleoside analogues. 3. The compound of claim 1 , wherein the hydroxyl protecting group is selected from a silyl group claim 1 , Calkyl claim 1 , Calkyl-O—Calkyl claim 1 , tetrahydropyranyl claim 1 , allyl claim 1 , benzyl claim 1 , —CH-naphthyl claim 1 , or benzoyl claim 1 , —C(═O)—Calkyl claim 1 , or —C(═O)-phenyl; wherein benzyl claim 1 , —CH-naphthyl claim 1 , and benzoyl claim 1 , are optionally substituted with one or two substituents each independently selected from —CHand —OCH; and/or the diol protecting group is C(Calkyl)-.4. The compound of claim 1 , wherein Y is O.5. The compound of claim 1 , wherein Y is CH.6. The compound of claim 1 , wherein n is 1.7. The compound of claim 6 , wherein:{'sup': 1', '2', 'a', 'a', 'a', 'a', 'a', 'c', 'a, 'sub': 2', 'm', '2', '2', 'm', '2', 'm', '2', 'm', '2', '2', 'm', '2', 'm', 'x', '1-6', '2, 'Ris hydrogen and R—(CH)NR, —(CH)OR, —(CH)C(O)OR, —(CH)C(O)NR, —(CH)C(O)R, —(CH)S(O)R, a silyl group, Calkyl substituted with a silyl group, ═O or ═CR; or'}{'sup': 2', '1', 'a', 'a', 'a', 'a', 'a', 'c', 'a, 'sub': 2', 'm', '2', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', '2', 'm', '2', 'm', 'x', '1-6', '2, 'Ris hydrogen and Ris —(CH)NR, —(CH)OR, —(CH)OPG, —(CH)C(O)OR, —(CH)C(O)NR, —(CH)C(O)R, —(CH)S(O)R, a silyl group, Calkyl substituted with a silyl group, —O-aryl, ═O or ═CR.'}8. The compound of claim 1 , wherein n is 0.9. The compound of claim 8 , wherein one of Rand Ris hydrogen and the other is —(CH)NR claim 8 , —(CH)OR claim 8 , —(CH)OPG claim 8 , —C(O)OR claim 8 , —C(O)NRor —B(OR).16. The compound of claim 15 , wherein Ris OR.20. The compound of claim 18 , wherein n is 1.21. The compound of claim 20 , wherein:{'sup': 1', '2', 'a', 'a', 'a', 'a', 'a', 'c', 'a, 'sub': 2', 'm', '2', '2', 'm', '2', 'm', '2', 'm', '2', '2', 'm', '2', 'm', 'x', '1-6', '2, 'Ris hydrogen and Ris —(CH)NR, —(CH)OR, —(CH)C(O)OR, —(CH)C(O)NR, —( ...

HYDROCINNAMOYL PROTECTED RIBOGUANOSINE PHOSPHORAMIDITES FOR DECREASING DEPYRIMIDINATION FROM ALKYL AMINE EXPOSURE DURING FINAL DEPROTECTION

Compounds useful for forming nucleic acids having the structure of Formula I: 3. The compound according to claim 2 , wherein the cyclic hydrocarbon has 5 to 6 carbon atoms.4. The compound according to claim 3 , wherein the cyclic hydrocarbon is selected from the group consisting of cyclopentyl claim 3 , cyclohexyl claim 3 , and phenyl claim 3 , and wherein Rand Rare each claim 3 , independently selected from 4 claim 3 ,4′-dimethoxytirtyl (DMT) and 2-cyanoethyl-(N claim 3 ,N-diisopropylamino)-phosphoramidite.7. The compound according to claim 6 , wherein the cyclic hydrocarbon has 5 to 6 carbon atoms.8. The compound according to claim 7 , wherein the cyclic hydrocarbon is selected from the group consisting of cyclopentyl claim 7 , cyclohexyl claim 7 , and phenyl claim 7 , and wherein Rand Rare each independently selected from 4 claim 7 ,4′-dimethoxytrityl (DMT) and 2-cyanoethyl-(N claim 7 ,N-diisopropylamino)-phosphoramidite.11. The method according to claim 10 , wherein said method further comprises exposing said internucleotide bond to an oxidizing agent.12. The method according to claim 10 , wherein said method further comprises removing said O-thiocarbon protecting group.13. The method according to claim 10 , wherein said nucleoside residue is covalently bound to a solid support.14. The method according to claim 13 , wherein said method further comprises cleaving said nucleic acid from said solid support to produce a free nucleic acid.17. The method according to claim 16 , wherein Q is G or C and the cyclic hydrocarbon is selected from the group consisting of cyclopentyl claim 16 , cyclohexyl claim 16 , and phenyl.18. The method according to claim 17 , wherein Q is G and the cyclic hydrocarbon is selected from the group consisting of cyclopentyl and phenyl. This application claims the benefit of U.S. Provisional Application No. 63/154,691, filed Feb. 27, 2021. The contents of the aforementioned application are hereby incorporated by reference in their entirety. ...

METHOD FOR PREPARING METAL NANOSTRUCTURE BASED ON BIOMOLECULES

The present invention relates to a method for preparing metal nanostructures using DNA, and more particularly, to a method for preparing metal nanostructures, in which a self-assembling DNA is used as a frame, and thus the orientation, shape and size of the nanostructures are easily controlled compared to conventional bottom-up methods. Metal nanostructures prepared by the method show excellent localized surface plasmon resonance properties, and thus can be used as fluorescent substances in drug delivery, biomedical imaging, supersensitive biosensors, etc. 1. A method for preparing a biomolecule-based metal nanostructure , the method comprising the steps of:(a) forming a self-assembled monomolecular layer of a biomolecule on the surface of a metal nanoseed, thereby forming a metal nanoseed-biomolecule complex; and(b) growing a metal ion on the surface of the complex while reducing the metal ion with a reducing agent.2. The method of claim 1 , wherein the metal nanoseed-biomolecule complex is prepared by the steps of:(i) binding a desthiobiotin-modified DNA to a streptavidin-modified magnetic particle to form a magnetic particle-DNA complex;(ii) binding the metal nanoseed to the DNA of the complex to form a magnetic particle-DNA-metal nanoseed complex; and(iii) adding a biotin solution to the magnetic particle-DNA-metal nanoseed complex to separate the bond between the magnetic particle and the DNA and remove the magnetic particle from the complex, thereby obtaining a metal nanoseed-DNA complex,wherein steps (i) to (iii) are repeatedly performed.3. The method of claim 2 , wherein step (i) further comprises claim 2 , after forming the magnetic particle-DNA complex claim 2 , a step of adding the magnetic particle-DNA complex to a mixture solution of EDC and NHS to activate the DNA.4. The method of claim 1 , wherein the metal nanoseed-biomolecule complex is prepared by the steps of:(i) treating the metal nanoseed surface with an oligonucleotide having a terminal ...

PROCESS FOR PREPARATION OF IRON SUCROSE

The present invention is directed to processes for preparation of iron sucrose complex and purification of the obtained iron sucrose through diafiltration. 1. A process for the preparation of iron-sucrose having molecular weight of 34 ,000 to 60 ,000 daltons comprising:(a) preparing iron sucrose crude by the reaction of ferric oxyhydroxide, sucrose, base in an aqueous medium;(b) optionally subjecting the iron sucrose crude obtained in stage (a), to diafiltration; and(c) contacting the iron sucrose obtained in stage (b) with additional sucrose to produce the iron-sucrose with desired molecular weight and particle size.2. The process of claim 1 , wherein in stage (a) claim 1 , the ferric oxyhydroxide is prepared in situ by the reaction of ferric salt with a base.3. The process of claim 2 , wherein the ferric salt is ferric chloride or its hydrate.4. The process of claim 1 , wherein in stage (a) claim 1 , the ferric salt claim 1 , sucrose and base are added initially in any order claim 1 , the ferric oxyhydroxide formed in situ will react with sucrose to produce crude iron sucrose complex.5. The process of claim 1 , wherein the iron sucrose complex formation takes place at a temperature of about 60° C. to about 120° C.6. The process according to claim 1 , wherein the iron sucrose complex formation takes place at a pH of 6 to 12.7. The process of claim 1 , wherein in stage (b) claim 1 , the diafiltration is carried out repeatedly till the desired quality is achieved.8. The process of claim 1 , wherein stage (c) claim 1 , additional sucrose and base are added to achieve the desired molecular weight.9. The process of claim 8 , wherein in stage (c) claim 8 , the reaction mass is heated to about 60° C. to about 120° C. after the addition of sucrose and base to get the desired molecular weight. This patent application claims priority to Indian Provisional Patent Application number 5383/CHE/2013 filed on Nov. 21, 2013, the contents of which are incorporated by reference ...

RUTHENIUM CARBON MONOXIDE RELEASING MOLECULES AND USES THEREOF

The present invention provides novel ruthenium compounds of Formula (I): or salts, isomers, hydrates, or solvates thereof, or combinations thereof; wherein E, R, R, R, R, R, X, and Xare as defined herein, and pharmaceutical compositions thereof. Also provided are methods of use and treatment. Such compounds have been found useful in the treatment of malaria infection. Such compounds may also be useful in the treatment of inflammatory conditions, such as acute lung injury and acute respiratory distress syndrome, which optionally may be associated with a malaria infection. 2. The compound of claim 1 , wherein E is —S—.3. The compound of claim 1 , wherein Ris —CH.4. The compound of claim 1 , wherein each instance of R claim 1 , R claim 1 , R claim 1 , and Ris hydrogen.5. The compound of claim 1 , wherein Xand Xare each —Cl.11. A pharmaceutical composition comprising a compound of claim 1 , or a salt claim 1 , isomer claim 1 , hydrate claim 1 , or solvate thereof claim 1 , or combination thereof claim 1 , and a pharmaceutically acceptable excipient.12. (canceled)13. A method of treating a malaria infection comprising administering an effective amount of a compound of claim 1 , or a salt claim 1 , isomer claim 1 , hydrate claim 1 , or solvate thereof claim 1 , or combination thereof claim 1 , to a subject in need thereof.1423-. (canceled)24. The method of claim 13 , wherein the method further comprises administering one or more anti-malarial additional agents.25. The method of claim 24 , wherein the one or more additional agents is selected from the group consisting of quinazolines claim 24 , protein kinase inhibitors claim 24 , quinines claim 24 , tetracyclines claim 24 , aminoquinolones claim 24 , biquanides claim 24 , cinchona alkaloids claim 24 , sulfonamides claim 24 , artemisinins claim 24 , clindamycin claim 24 , dapsone claim 24 , atovaquone claim 24 , lumefantrine claim 24 , piperaquine claim 24 , pyronaridine claim 24 , atovaquone claim 24 , mefloquine claim 24 ...

Labeled Nucleic Acids: A Surrogate for Nanopore-based Nucleic Acid Sequencing

Materials, methods, and systems for determining the sequence of a target nucleic acid are disclosed and described. Materials can include ssDNA, ssRNA, and dsDNA. Materials are first transformed to partially or fully osmylated single-stranded nucleic acid (osmylated or labeled polymer) after reaction with Osmium tetroxide 2,2′-bipyridine which labels selectively Thymidine over Cytidine, but leaves purines intact. Methods are provided to describe preparation of the osmylated polymers, their purification, and characterization. Labeled polymers are subject to voltage-driven translocation via nanopores of appropriate width so that the polymer can traverse as a single-file. The translocation is monitored and reported as a current vs. time (i-t) profile. The current is stable, but fluctuates during the polymer's translocation in a manner that pinpoints the osmylated bases interspersed among the intact bases. Methods are also described so that the events within the i-t profile unravel the sequence of the target nucleic acid. 1. Methods for preparing osmylated nucleic acids (osmylated or labeled polymers) comprising:Using Osmium tetroxide 2,2′-bipyridine of a recommended preparation at recommended conditions in order to selectively label T or T+C or at alternative levels of osmylation;purifying the product by one or more purification methods to remove the unreacted label;and using one or more analytical methods to characterize the article and confirm extent of labeling by the disclosed assay.2. A method of determining the sequence of pyrimidines of the osmylated polymer , comprising:applying an electric field across a nanopore disposed between a first conductive liquid medium and a second conductive liquid medium andmeasuring an ion current to provide a threshold amount in the absence of the article and thenmeasuring the changed current pattern (i-t) while the labeled polymer traverses through the nanopore.3. A method of assigning changes in i-t measurements from the ...

POLYENE MACROLIDE DERIVATIVE

The present invention is the following Amphotericin B derivative: 1. A method for treating a fungal infection, which comprises administrating the effective doses for antifungal of a compound defined below to human or animals: This application is a divisional of copending application Ser. No. 15/315,646 filed on Dec. 1, 2016, which is the National Phase under 35 U.S.C. § 371 of International Application No. PCT/JP2015/066976 filed on Jun. 12, 2015, which claims the benefit under 35 U.S.C. § 119(a) to Patent Application No. 2014-121341, filed in Japan on Jun. 12, 2014, all of which are hereby expressly incorporated by reference into the present application.The present invention relates to polyene macrolide derivatives. Especially, the present invention relates to polyene macrolide derivatives which are useful for treatment or prevention against fungal infection of human or animals.Amphotericin B is known as a drug having microbicidal effect by binding to ergosterol of cell membrane of fungi and forming ostium to membrane from long ago. Amphoteiricn B is used as formulation using deoxycholic acid or liposome due to its low water solubility and high toxicity. However, the formulation using deoxycholic acid is still high toxicity, so satisfactory administration and long-term treatment cannot be achieved. The formulation using liposome can greatly avoid possibility of hepatotoxicity and nephrotoxicity compared with the formulation using deoxycholic acid, but effective treatment is not still actually achieved because of decrease of drug efficacy (Non-patent Document 1, 2).Therefore, chemical modification of amphotericin B has been tried for the improvement of its water solubility or the avoidance of its toxicity. For example, amphotericin B derivative having amide at 16th position (Patent Document 1, 3, 4, 5, 10) and ester derivative (Patent Document 2, 6, 7, 9, 11) are disclosed. In addition, amphotericin B derivatives having a modification at amino sugar part are ...

LIPID-BASED PLATINUM COMPOUNDS AND NANOPARTICLES

The present disclosure is in relation to the field of nanotechnology and cancer therapeutics. In particular, the present disclosure relates to platinum based compounds comprising platinum moiety, linker moiety and lipid moiety and corresponding nanoparticles thereof. The disclosure further relates to synthesis of said platinum based compounds, nanoparticles and compositions comprising said platinum based compounds/nanoparticles. The disclosure also relates to methods of managing cancer by employing aforesaid carbene compounds, platinum based compounds, nanoparticles and compositions thereof. 1. A compound comprising:(a) a platinum moiety; and(b) a lipid connected to said platinum moiety.2. The compound of claim 1 , wherein the compound comprises a carbonyl moiety.3. The compound of claim 2 , wherein the carbonyl moiety is a carboxylic acid selected from the group consisting of succinic acid claim 2 , malonic acid claim 2 , oxalic acid claim 2 , keto acid claim 2 , and any combination thereof.4. The compound of claim 1 , wherein the platinum atom is conjugated to said lipid via covalent bond claim 1 , coordinate bond or a combination thereof.5. The compound of claim 1 , wherein the compound comprises at least one linker between the platinum moiety and the lipid.9. (canceled)10. The compound of claim 5 , wherein the linker is selected from the group consisting of:{'sub': 2', '2', '1', '1', '2', '2', '2', 'n, '(i) —X—CH—X—X—, wherein X is NH; Xis C(O)O, C(O)NH, O(CH)—O, NH, or O; Xis (CH)or C(O); and n is 0, 1, 2, 3, 4, or 5;'}{'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'm', '2', 'n', '2', 'm', '2', 'n', '2', 'n', '2', 'm', '2', 'n, '(ii) —(CH)O—, —(CH)NHC(O)O—, —(CH)OC(O)NH—, —(CH)C(O)NH(CH)O—, —(CH)O(CH)O—, —(CH)O(O)—, —(CH)NHC(O)(CH)O—, or —(CH)C(O)O—; wherein n and m are independently 0, 1, 2, 3, 4, or 5;'}{'sub': 3', '4', '5', '6', '3', '2', '4', '5', '6', '2, '(iii) —X—XX—X, wherein Xis CH, CH, or O; and X, Xand Xare independently same or different and ...

PHOSPHOROAMIDATE ESTERS, AND USE AND SYNTHESIS THEREOF

Phosphoramidate esters and related nucleotide analogs useful in polynucleotide sequencing techniques, and synthetic methods for preparing those compounds, are disclosed. These compounds include nucleotide phosphoramidates analogs that are modified on the alpha-phosphate to enable attachment of a variety of application-specific substituents such as tether molecules. 2. The compound of wherein each of Rand Ris selected from an alkyl group and an oxyalkyl group claim 1 , either of which terminates in a functional group selected from carbon-carbon double bond claim 1 , carbon-carbon triple bond claim 1 , hydroxyl claim 1 , amine claim 1 , azide claim 1 , hydrazine claim 1 , thiol claim 1 , carboxyl claim 1 , formyl claim 1 , hydroxylamino and halogen.3. The compound of wherein each of Rand Ris selected from an alkyl group and an oxyalkyl group claim 1 , either of which terminates in a linker group (LG1) claim 1 , the LG1 bonded to a tether (T).4. The compound of wherein LG1 and LG2 are triazole groups.5. The compound of wherein Ris —(CH)—C≡CH and q is an integer selected from 2-10.9. The compound of wherein Ris —C≡C—(CH)—C≡CH.13. The compound of wherein each of LG1 and LG2 is a triazole group.18. The process of further comprising reacting the N-phosphoroamidate-monoester triphosphate (160) with a tether precursor of the formula X-T-X where X represents a reactive functional group that is reactive with the terminating functional group of Rand R claim 17 , so as to form linker groups LG1 and LG2.19. The process of wherein X is an azide group and the terminating functional groups of Rand Rare alkyne groups. The present invention is in the field of phosphoroamidate ester compounds, synthetic methods for making said compounds, and methods for the determination of nucleic acids using said compounds, e.g., in the field of single molecule sequencing.Chemically modified nucleotides have been extensively used in the study of many complicated biological systems. In particular, ...

Intermediate for Production of Nucleoside Analog and Method for Producing the Same

A compound represented by the general formula (III) which serves as an intermediate of an oligonucleotide analog having stable and excellent antisense or antigene activity or having excellent activity as a detection reagent (probe) for a specific gene or as a primer for the initiation of amplification of a specific gene can be produced at high yields regardless of the type of nucleobase by a method comprising reacting a compound represented by the general formula (II) or a salt thereof with a trimethylsilylated compound obtained from a compound represented by the general formula (IVb), wherein X, Y, Z, A, R, and B are as defined in claim 2. The method of claim 1 , wherein X is a methyl group substituted by 1 to 3 aryl groups claim 1 , or a methyl group substituted by 1 to 3 aryl groups wherein the aryl ring is substituted by a lower alkyl claim 1 , lower alkoxy claim 1 , halogen claim 1 , or cyano group.3. The method of claim 1 , wherein X is a benzyl group claim 1 , a p-methoxybenzyl group claim 1 , a dimethoxytrityl group claim 1 , or a monomethoxytrityl group.4. The method of claim 1 , wherein Y is a methyl group substituted by 1 to 3 aryl groups claim 1 , or a methyl group substituted by 1 to 3 aryl groups wherein the aryl ring is substituted by a lower alkyl claim 1 , lower alkoxy claim 1 , halogen claim 1 , or cyano group.5. The method of claim 1 , wherein Y is a benzyl group claim 1 , a β-naphthylmethyl group claim 1 , or a p-methoxybenzyl group.6. The method of claim 1 , wherein Z is an aliphatic acyl group having 2 to 4 carbon atoms.7. The method of claim 1 , wherein Z is an acetyl group.8. The method of claim 1 , wherein A is a methylene group or an ethylene group.9. The method of claim 1 , wherein A is a methylene group.10. The method of claim 1 , wherein B is a 6-aminopurin-9-yl group claim 1 , a 6-aminopurin-9-yl group with the amino group protected claim 1 , a 2 claim 1 ,6-diaminopurin-9-yl group claim 1 , a 2-amino-6-chloropurin-9-yl group claim 1 , a ...

SILICA PARTICLES COATED WITH BETA-CYCLODEXTRIN FOR THE REMOVAL OF EMERGING CONTAMINANTS FROM WASTEWATER

Provided is a silica particle coated with β-cyclodextrin, wherein said cyclodextrin is attached to said silica particle via at least one crosslinking agent and/or at least one copolymer. Also provided are methods of removing contaminants from a flowing or stationary liquid phase comprising the step of contacting said liquid phase with the silica particle coated with β-cyclodextrin. 1. A silica particle coated with β-cyclodextrin polymer , wherein said β-cyclodextrin polymer is formed by polymerizing β-cyclodextrin with(i) hexamethylene diisocyanate, wherein the molar ratio of β-cyclodextrin: hexamethylene diisocyanate in said polymerization is from about 1:7 to about 1:15 and wherein the molar ratio of β-cyclodextrin:silica in said polymerization is from about 1:15 to about 1:30; or(ii) epichlorohydrin, wherein the molar ratio of β-cyclodextrin: epichlorohydrin in said polymerization is from about 1:7 to about 1:9 and wherein the molar ratio of β-cyclodextrin:silica in said polymerization is from about 1:83 to about 1:125.2. A silica particle modified with a functional group on its surface and coated with β-cyclodextrin , wherein said β-cyclodextrin is attached to said silica particle via a chemical bond to the functional group on the surface of the silica.3. The silica particle of wherein said functional group is formed by chemical reaction of said silica with a compound selected from the group consisting of glycidoxypropyl trimethoxysilane and aminopropyl triethoxysilane.4. A silica particle modified with a functional group on its surface and coated with β-cyclodextrin polymer claim 2 , wherein said β-cyclodextrin polymer is formed by polymerizing β-cyclodextrin with hexamethylene diisocyanate or epichlorohydrin and wherein said β-cyclodextrin polymer is attached to said silica particle via a chemical bond to the functional group on the surface of the silica.5. The silica particle of wherein said functional group is formed by chemical reaction of said silica with ...

Composition of iron sucrose and process for its preparation

The present invention relates to composition of iron sucrose and process for its preparation. The present invention also related to a process for the preparation of iron sucrose suitable for the iron sucrose composition.

METHODS OF PRODUCING C-ARYL GLUCOSIDE SGLT2 INHIBITORS

Method for the production of C-aryl glucoside SGLT2 inhibitors useful for the treatment of diabetes and related diseases. and intermediates thereof. The C-aryl glucosides may be complexed with amino acid complex forming reagents. 2. The method of wherein the acid labile protecting group is selected from the group consisting of methoxymethyl ether claim 1 , methylthiomethyl ether claim 1 , 2-methoxyethoxymethyl ether claim 1 , bis(2-chloroethoxy)methyl ether claim 1 , tetrahydropyranyl ether claim 1 , tetrahydrothiopyranyl ether claim 1 , 4-methoxytetrahydropyranyl ether claim 1 , 4-methoxytetrahydrothiopyranyl ether claim 1 , tetrahydrofuranyl ether claim 1 , tetrahydrothiofuranyl ether claim 1 , 1-ethoxyethyl ether claim 1 , 1-methyl-1-methoxyethyl ether claim 1 , 2-(phenylselenyl)ethyl ether claim 1 , t-butyl ether claim 1 , allyl ether claim 1 , triphenylmethyl ether claim 1 , α-naphthyldiphenylmethyl ether claim 1 , p-methoxyphenyldiphenyl methyl ether claim 1 , trialkylsilyl ether claim 1 , trimethylsilyl ether claim 1 , triethylsilyl ether claim 1 , isopropyldimethylsilyl ether claim 1 , t-butyldimethylsilyl ether claim 1 , t-butyldiphenylsilyl ether and combinations thereof.3. The method of wherein the acid labile protecting group is selected from the group consisting of methoxymethyl ether claim 2 , 2-methoxyethoxymethyl ether claim 2 , tetrahydropyranyl ether claim 2 , trimethylsilyl ether claim 2 , isopropyldimethylsilyl ether claim 2 , t-butyldimethylsilyl ether claim 2 , t-butyldiphenylsilyl ether claim 2 , and combinations thereof.5. The method of wherein Y is selected from the group consisting of alkali metals claim 4 , and alkaline earth metals.6. The method of further comprising reacting D-glucono-1 claim 4 ,5-lactone with an acid labile protecting group providing reagent to form the compound of Formula (II).7. The method of wherein the acid labile protecting group providing reagent is selected from the group consisting of trimethylsilylchloride ...

METHOD AND KIT FOR DETECTION OF CYANIDE

A metal contamination detection system, forming part of a cyanide detection system, comprising a solid buffer, the buffer being adapted to provide a pH of from 9-10. 1. A metal contamination detection system , forming part of a cyanide detection system , comprising a solid buffer , the buffer being adapted to provide a pH of from 9-10.2. The metal contamination detection system according to claim 1 , in which the buffer is selected from the group consisting of a N-cyclohexyl-2-aminoethanesulfonic acid (CHES) buffer claim 1 , Carbonate-Bicarbonate Buffer (Carbonate) claim 1 , Glycine Buffer (Glycine) claim 1 , 2-Amino-2-Methyl-1-Propanol (AMP) buffer claim 1 , and 2-Amino-2-methyl-1 claim 1 ,3-propanediol (AMPD) buffer.3. The metal contamination system according to claim 2 , in which the buffer is CHES.4. A method of detecting metal contamination in a cyanide detection system claim 2 , comprising adding a test sample to a solid buffer prior to testing for cyanide.5. The method according to claim 4 , in which the buffer is selected from the group consisting of Carbonate-Bicarbonate Buffer (Carbonate) claim 4 , Glycine Buffer (Glycine) claim 4 , 2-Amino-2-Methyl-1-Propanol (AMP) buffer claim 4 , 2-Amino-2-methyl-1 claim 4 ,3-propanediol (AMPD) buffer and CHES buffer.6. The method according to claim 4 , in which the buffer is CHES.8. The cyanide detection kit according to claim 7 , in which in which the buffer is selected from the group consisting of a CHES buffer claim 7 , Carbonate-Bicarbonate Buffer (Carbonate) claim 7 , Glycine Buffer (Glycine) claim 7 , 2-Amino-2-Methyl-1-Propanol (AMP) buffer claim 7 , and 2-Amino-2-methyl-1 claim 7 ,3-propanediol (AMPD) buffer.9. The cyanide detection kit according to claim 8 , in which the buffer is a CHES buffer. This disclosure relates to the detection of cyanide and to methods for doing so. More particularly, it relates to the detection of impurities that could give false results.Cyanide compounds are essential substances in ...

RADIATION ENHANCED MACROMOLECULAR DELIVERY OF THERAPEUTIC AGENTS FOR CHEMOTHERAPY

Described herein are anti-cancer compounds composed of a macromolecule comprising (1) at least one anti-cancer agent directly or indirectly bonded to the macromolecule and (2) at least one high Z element directly or indirectly bonded to the macromolecule that is capable of producing Auger electrons upon exposure to X-ray energy. When the compounds are exposed to low energy X-ray (e.g., kilo electron volts KeV) Auger electrons are produced by the high Z elements present in the compound. Because lower energy is required when compared to typical radiotherapy, which uses therapeutic X-ray energy in the million electron volt range (MeV), the subject experiences lower collateral damage when compared to radiation therapy. Additionally, the presence of the anti-cancer agent provides a second mechanism for killing cancer cells. Methods for making and using the anti-cancer compounds are also described herein. 1. A compound comprising a macromolecule comprising (1) at least one anti-cancer agent directly or indirectly bonded to the macromolecule and (2) at least one high Z element directly or indirectly bonded to the macromolecule that is capable of producing Auger electrons upon exposure to X-ray energy.3. The compound of claim 1 , wherein the macromolecule comprises dextran claim 1 , dextrin claim 1 , hyaluronic acid claim 1 , chitosan claim 1 , polylactic/glycolic acid (PLGA) claim 1 , poly lactic acid (PLA) claim 1 , polyglutamic acid (PGA) claim 1 , polymaleic acid claim 1 , polyaspartamides claim 1 , polyethylene glycol (PEG N-(2-hydroxypropyl) methacrylamide (HPMA) claim 1 , polyvinylpyrrolidone claim 1 , polyethyleneimine claim 1 , polyamidoamine (linear) claim 1 , poly(amido amine) (PAMAM) claim 1 , diaminobutane (DAB) claim 1 , diaminoethane (DAE) claim 1 , and a dendrimer comprising polyamidoamine claim 1 , polypropyleneimine claim 1 , polyether claim 1 , polylysine claim 1 , or any combination thereof.4. The compound of claim 1 , wherein the macromolecule comprises ...

TRANSITION METAL MOLYBDOTUNGSTEN OXY-HYDROXIDE

A hydroprocessing catalyst has been developed. The catalyst is a unique transition metal molybdotungsten oxy-hydroxide material. The hydroprocessing using the transition metal molybdotungsten oxy-hydroxide material may include hydrodenitrification, hydrodesulfurization, hydrodemetallation, hydrodesilication, hydrodearomatization, hydroisomerization, hydrotreating, hydrofining, and hydrocracking. 2. The transition metal molybdotungsten oxy-hydroxide material of wherein the transition metal molybdotungsten oxy-hydroxide material is present in a mixture with at least one binder and wherein the mixture comprises up to 25 wt % binder.3. The transition metal molybdotungsten oxy-hydroxide material of wherein the binder is selected from the group consisting of silicas claim 2 , aluminas claim 2 , and silica-aluminas.4. The transition metal molybdotungsten oxy-hydroxide material of wherein M is nickel or cobalt.5. The transition metal molybdotungsten oxy-hydroxide material of wherein M is nickel.6. The transition metal molybdotungsten oxy-hydroxide material of wherein the transition metal molybdotungsten oxy-hydroxide material is sulfided.8. The method of wherein the reacting is conducted at a temperature ranging from about 60° C. to about 120° C. for a period of time ranging from 30 minutes to around 2 days.9. The method of wherein the recovering is by filtration or centrifugation.10. The method of further comprising adding a binder to the recovered metal molybdotungsten oxy-hydroxide material11. The method of wherein the binder is selected from the group consisting of aluminas claim 10 , silicas claim 10 , and alumina-silicas.12. The method of further comprising sulfiding the recovered transition metal molybdotungsten oxy-hydroxide material.14. The process of wherein the conversion process is hydroprocessing.15. The process of wherein the conversion process is selected from the group consisting of hydrodenitrification claim 13 , hydrodesulfurization claim 13 , ...

HOST-GUEST METAL ORGANIC FRAMEWORK SYSTEMS

The present invention relates to a method for producing Metal Organic Framework (MOF) having a framework that encapsulates a bio-molecule, the method comprising combining in a solution the bio-molecule and MOF precursors, wherein the bio-molecule promotes formation of the encapsulating framework. 1. A method for producing Metal Organic Framework (MOF) having a framework that encapsulates a bio-molecule , the method comprising combining in a solution the bio-molecule and MOF precursors , wherein the bio-molecule promotes formation of the encapsulating framework.2. A method of producing crystalline Metal Organic Framework (MOF) having a framework that defines intrinsic cavities and encapsulates a bio-molecule , said method comprising:combining in a solution MOF precursors and a bio-molecule, the bio-molecule promoting formation of the encapsulating framework,wherein the bio-molecule has a smallest dimension that is larger than the largest cavity diameter (LCD) of any intrinsic cavity of the framework.3. The method according to claim 2 , wherein the smallest dimension of the bio-molecule is at least 1.5 times larger than the LCD of any intrinsic cavity of the framework.4. The method according to claim 2 , wherein the LCD is between 5 Å and 500 Å.5. The method according to claim 1 , wherein the bio-molecule is a protein claim 1 , a nucleic acid claim 1 , an amino acid or a combination thereof.6. The method according to claim 1 , wherein the bio-molecule is a protein which is an enzyme.7. The method according to claim 1 , wherein the bio-molecule is a protein and has a concentration in the solution of between 0.1 and 20 mg/mL.8. The method according to claim 1 , wherein the bio-molecule is an amino acid and has a concentration in the solution of between 0.1 and 100 mg/mL.9. The method according to claim 1 , wherein the bio-molecule is a nucleic acid and has a concentration in the solution of between 0.001 and 100 μM.10. The method according to claim 1 , wherein the MOF ...

SYNTHETIC pGpG ANALOGS, METHODS OF PREPARATION AND METHODS OF USE

The present invention relates to compounds according to Formula I: and salts thereof, wherein R, R, R, R, and L are as defined herein. Methods for preparing compounds of Formula I are also provided. The present invention further includes methods of treating and preventing bacterial infections, and methods of identifying pGpG-binding domains in bacteria, using the compounds of Formula I. 2. A compound according to claim 1 , or a salt thereof claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , and Ris hydrogen.3. A compound according to or a salt thereof claim 2 , wherein at least one of Rand Ris hydrogen.6. A compound according to claim 5 , selected from the group consisting of:3-((((2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl)amino)-4-(((2S,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-4-hydroxy-2-(hydroxymethyl)tetrahydrofuran-3-yl)amino)cyclobut-3-ene-1,2-dione;3-((((2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)amino)-4-(((2S,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-4-hydroxy-2-(hydroxymethyl)tetrahydrofuran-3-yl)amino)cyclobut-3-ene-1,2-dione, and a salt thereof.8. A method of treating an individual suffering from a bacterial infection claim 1 , comprising administering to the individual an effective amount of at least one compound or a pharmaceutically acceptable salt thereof claim 1 , according to .9. A method of preventing bacterial infection in an individual claim 1 , comprising administering to the individual an effective amount of at least one compound or a pharmaceutically acceptable salt thereof claim 1 , according to .10. A method of reducing the risk of bacterial infection in an individual claim 1 , comprising administering to the individual an effective amount of at least one compound or a pharmaceutically acceptable salt thereof claim 1 , according to .11. The method according to claim 8 , comprising administering to the individual an effective ...

REGIOSELECTIVE SILYL EXCHANGE OF PER-SILYLATED OLIGOSACCHARIDES

The present invention provides novel, regioselectively-acylated oligosaccharide compounds and methods for preparing them. In another aspect, the. invention provides a method for preparing a selectively-acylated oligosaccharide. The method includes forming a reaction mixture containing a protected oligosaccharide and an acylating agent. The protected oligosaccharide includes at least three hydroxyl moieties and each hydroxyl moiety is protected with a silyl protecting group. The reaction mixture is formed under conditions sufficient to selectively replace at least one silyl protecting group with a —C(0)-C1_6 alkyl group, and the selectively-acylated oligosaccharide comprises at least one —C(0)-C1_6 alkyl group and at least one silyl protecting group. 2. The compound according to claim 1 , wherein{'sup': 1', '2', '3', '4', '6', '7, 'R, R, R, R, and Rare each independently selected from the group consisting of —OR, the α-linked monosaccharide, and the β-linked monosaccharide;'}{'sup': 1a', '2a', '3a', '4a', '6a', '7, 'R, R, R, R, and Rare each independently selected from the group consisting of —ORand the linking moiety —O—;'}{'sup': '7', 'sub': 1-6', '3, 'each Ris independently selected from the group consisting of —C(O)—Calkyl and —Si(R); and'}{'sup': 1', '2', '3', '4', '6', '1a', '2a', '3a', '4a', '6a', '7', '7', '8, 'sub': '3', 'at least one of R, R, R, R, R, R, R, R, R, and Ris —OR, wherein Ris —Si(R).'}3. The compound according to claim 2 , wherein Ris selected from the group consisting of the α-linked monosaccharide and the β-linked monosaccharide.46-. (canceled)911-. (canceled)15. (canceled)1720-. (canceled)21. The method according to claim 14 , wherein the reaction mixture further comprises an acid selected from the group consisting of acetic acid claim 14 , formic acid claim 14 , and trichloroacetic acid.22. (canceled)23. The method according to claim 14 , wherein the reaction mixture further comprises at least one base selected from the group consisting of ...

Cancer cell specific imaging probes and methods of use

The present invention provides a compound having the structure: wherein X is an imaging agent containing at least one amine nitrogen; Y is a chemical linker, wherein Y is present or absent, and when present Y is a chemical linker containing at least one amine nitrogen or Y is a para-aminobenzyl alcohol linker; Z is CH 3 or CF 3 ; R 1 is —H, —NR 2 R 3 , —NH—C(═O)—R 4 , —NH—C(═O)—OR 4 , —CH 2 —C(═O)—NR 5 R 6 , —OR 7 , —CO 2 R 7 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, or heteroaryl, wherein R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each, independently, —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, an amino acid or an oligopeptide; wherein an amine of the amino acid or oligopeptide is substituted or unsubstituted; and n is an integer from 0 to 6; or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

VIRUS DETECTION

The invention provides methods and materials for use in the detection of influenza viruses which utilise a nanoparticle, for example gold nanoparticle, probe comprising a plurality of glycoconjugate ligands, each glyconjugate ligand (GL) having a plurality of sialic-acid containing recognition group (Y) coupled to the nanoparticle via a multivalent core (X), wherein the multivalent core (X) is a trivalent core, whereby there are 3 recognition groups per ligand, wherein the recognition groups on the bioconjugate specifically bind to the hemagglutinin on the target influenza virus. The probes may include further ligands bound to the nanoparticle which do not bind specifically to an influenza virus—for example polyethylene glycol groups. These can modulate density of the glycoconjugate ligand on the surface of the nanoparticle. Binding of probes is detected by a plasmonic signal which is specific to the influenza virus. 151.-. (canceled)52. A nanoparticle probe comprising a plurality of glycoconjugate ligands ,each glyconjugate ligand (GL) having a plurality of sialic-acid containing recognition groups (Y) coupled to the nanoparticle via a multivalent core (X),wherein the multivalent core (X) is a trivalent core, whereby there are 3 recognition groups per ligand,wherein the recognition groups on the bioconjugate specifically bind to the hemagglutinin on a target influenza virus,wherein the probe has at least one further type of ligand bound to the nanoparticle, wherein the further type of ligand is one which does not bind specifically to the target influenza virus.53. The nanoparticle probe of claim 52 , wherein the or each recognition group terminates with the α-anomer of a sialic acid moiety claim 52 , and the sialic acid moiety is bound to a monosaccharide through a 2 claim 52 ,6 glycosidic bond or 2 claim 52 ,3 glycosidic bond.54. The nanoparticle probe of claim 53 , wherein the target influenza virus is a human influenza virus or avian influenza virus.55. The ...

SILYL ETHERIFIED DERIVATIVES OF 5-AZACYTIDINES IN CARBOHYDRATE MOIETY

The present invention relates to a prodrug of 5-azacytidine or 2′-deoxy-5-azacytidine having remarkable stability against cytidine deaminase, a metabolic hydrolyzing enzyme in replacement of current injections (5-azacytidine or 2′-deoxy-5-azacytidine) which are clinically used as therapeutic agents for various myelomas including myelodysplastic syndrome. The present invention provides a compound represented by formula (1), or salt thereof, 2. The compound according to claim 1 , wherein Ris a silyl group represented by the formula (2) claim 1 , while Ris hydrogen atom.3. The compound according to claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently Cto Calkyl group claim 1 , which may have a substituent claim 1 , Cto Caryl group claim 1 , which may have a substituent or Cto Carylalkyl group claim 1 , which may have a substituent.4. The compound according to claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently Cto Calkyl group claim 1 , which may have a substituent.5. The compound according to claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently Cto Ccycloalkyl group claim 1 , which may have a substituent.6. The compound according to claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently Cto Ccycloalkyl group claim 1 , which may have a substituent.8. The compound according to claim 7 , wherein R claim 7 , R claim 7 , and Rare each independently Cto Ccycloalkyl group claim 7 , which may have a substituent.9. The compound according to claim 7 , wherein R claim 7 , R claim 7 , and Rare each independently Cto Ccycloalkyl group claim 7 , which may have a substituent.10. A method for producing the compound or salt thereof claim 1 , according to claim 1 , the method comprising: reacting 5-azacytidine or 2′-deoxy-5-azacytidine with silyl halide.11. A pharmaceutical composition claim 1 , which comprises the compound claim 1 , or salt thereof claim 1 , according to .12. A method for treatment of a symptom claim 1 ...

BORON-CONTAINING COMPOUND

To provide a novel boron-containing compound. A compound represented by the following formula: wherein black circle represents B, white circles represent B—H; —Rrepresents —(CH)n-X—R(n represents an integer of 0 to 6; Xrepresents O, S, NH, S—S, O—CO, NHCO or SCO, or does not exist; Rrepresents C-Calkyl, hydroxy C-Calkyl, amino C-Calkyl, azido C-Calkyl, hydroxycarbonyl C-Calkyl, or the like), or a group having a repeating sequence of —(CH)—O— 3 times or more and 10 times or less and having a methyl group or an ethyl group at the end on the oxygen atom side; and —Ris —(CH)m-X—R(m represents an integer from 0 to 8; Xrepresents O, S, NH, S—S, O—CO, NHCO or SCO, or does not exist; and Rrepresents a tumor recognition moiety), or does not exist 13. A pharmaceutical composition comprising one or more compounds according to .14. The pharmaceutical composition according to claim 13 , which is used for treating cancer with BNCT. The present invention relates to a boron-containing compound and a method for producing the same. The boron-containing compound of the present invention can be applied to various applications. For example, the boron-containing compound of the present invention is useful as a neutron capture therapy agent for use in boron neutron capture therapy (BNCT).Recently, attention has been drawn to a boron neutron capture therapy (BNCT) as a novel cancer treatment method utilizing a radioisotope. The boron neutron capture therapy is a treatment method in which a boron-containing compound containing boron-10 isotope (B) is delivered to cancer cells and the cancer cells are irradiated with a low energy neutron (for example, thermal neutrons), and thus the cancer cells are locally destroyed by a nuclear reaction which arises in the cells. In this treatment method, since it is important to cause a boron-containing compound which contain B to be selectively accumulated by cells of cancerous tissue so as to enhance therapeutic effect, boron-containing compounds which ...

ASYMMETRIC AUXILIARY GROUP

To provide a chiral reagent or a salt thereof. The chiral reagent has following chemical formula (I). In the formula (I), Gand Gare independently a hydrogen atom, a nitro group (—NO), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both Gand Gtaken together to form a group of formula (IV). 3. The chiral reagent or a salt thereof in accordance with claim 2 , wherein each of Gand Gis a group of formula (II) claim 2 , wherein Gto Gare independently a hydrogen atom claim 2 , a nitro group claim 2 , a halogen atom claim 2 , a cyano group or Calkyl group.4. The chiral reagent or a salt thereof in accordance with claim 2 , wherein each of Gand Gis a group of formula (II) claim 2 , wherein each of Gto Gis a hydrogen atom.5. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (II) claim 2 , wherein Gto Gare independently a hydrogen atom claim 2 , a nitro group claim 2 , a halogen atom claim 2 , a cyano group or Calkyl group.6. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and Gis a group of formula (II) claim 2 , wherein each of Gand Gis a hydrogen atom and Gis a nitro group.7. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , Caryl group claim 2 , Caralkyl group claim 2 , Calkyl Caryl group claim 2 , Calkoxy Caryl group claim 2 , or Caryl Calkyl group.8. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom claim 2 , and Gis a group of formula (III) claim 2 , wherein Gto Gare independently Calkyl group claim 2 , Caryl group claim 2 , Caralkyl group claim 2 , Calkyl Caryl group claim 2 , Calkoxy Caryl group claim 2 , or Caryl Calkyl group.9. The chiral reagent or a salt thereof in accordance with claim 2 , wherein Gis a hydrogen atom and ...

METHODS OF PREPARING SUBSTITUTED NUCLEOSIDE ANALOGS

Disclosed herein are methods of preparing a nucleoside analog, which are useful in treating diseases and/or conditions such as viral infections, and intermediates thereof. 2. The method of claim 1 , wherein the silyl group is selected from the group consisting of trimethylsilyl (TMS) claim 1 , triethylsilyl (TES) claim 1 , dimethylisopropylsilyl (IPDMS) claim 1 , diethylisopropylsilyl (DEIPS) claim 1 , tert-butyldimethylsilyl (TBDMS) claim 1 , triisopropylsilyl (TIPS) claim 1 , tert-butyldiphenylsilyl (TBDPS) claim 1 , tri-iso-propylsilyloxymethyl claim 1 , [2-(trimethylsilyl)ethoxy]methyl claim 1 , tetraisopropyldisilylene (TIPDS) and di-tert-butyldimethylsilylene (DTBS).3. The method of claim 2 , wherein the silyl group is a triisopropylsilyl (TIPS) group.4. The method of claim 1 , wherein the triarylmethyl group is selected from the group consisting of trityl claim 1 , monomethoxytrityl (MMTr) claim 1 , 4 claim 1 ,4′-dimethoxytrityl (DMTr) and 4 claim 1 ,4′ claim 1 ,4″-trimethoxytrityl (TMTr).6. The method of claim 5 , wherein the chlorinating reagent is LiCl.8. The method of claim 7 , wherein the 7-membered ring is cleaved using an acid.9. The method of claim 8 , wherein the acid is HCl.11. The method of claim 10 , wherein the silyl group is removed using a fluoride source.12. The method of claim 11 , wherein the fluoride source is selected from the group consisting of tetrabutylammonium fluoride claim 11 , pyridine.HF claim 11 , triethylamine trihydrofluoride claim 11 , hydrofluoric acid claim 11 , tris(dimethylamino)sulfonium difluorotrimethylsilicate claim 11 , SiFand ammonium fluoride13. The method of claim 12 , wherein the fluoride source is tetra-n-butylammonium fluoride.15. The method of claim 14 , wherein the acyl groups are formed via an esterification reaction using isobutyric anhydride.16. The method of any one of - claim 14 , further comprising using 4-dimethylaminopyridine as a catalyst.19. The method of claim 18 , wherein the cyclization is ...

PROTECTED MONOMER AND METHOD OF FINAL DEPROTECTION FOR RNA SYNTHESIS

A method of deprotecting a solid support bound polynucleotide comprising at least one 2′-protected ribonucleotide in which a step of contacting the polynucleotide with a composition comprising a diamine is performed under conditions sufficient to deprotect and cleave the polynucleotide which remains retained on the solid support. 1. A method of deprotecting a polynucleotide bound to a solid support with a linker , the polynucleotide comprising at least one 2′-protected ribonucleotide having a phosphate protecting group , a 2′-protecting group , and optionally a nucleobase-protecting group; the method comprising:(a) contacting the solid support bound polynucleotide with a first composition comprising a phosphate deprotection reagent and removing the phosphate protecting group, thereby producing a first deprotected polynucleotide bound to the solid support;(b) contacting said first deprotected polynucleotide bound to the solid support with a second composition comprising a 2′-deprotection reagent and removing the 2′-protecting group, thereby producing a second deprotected polynucleotide bound to the solid support; and(c) after step (b) has been completed, contacting said second deprotected polynucleotide bound to the solid support with a third composition comprising a diamine in organic solvent, gas-phase or neat, and cleaving the linker and also removing the nucleobase protecting group, if present, and thereby producing a deprotected, cleaved polynucleotide which is retained on the solid support.2. The method of claim 1 , wherein the method further comprises:(d) washing the deprotected, cleaved polynucleotide retained on the solid support with an organic solvent; and(e) eluting the deprotected, cleaved polynucleotide from the solid support.3. The method of claim 1 , wherein said 2′-protecting group is selected from tertbutyldimethylsilyl (TBDMS) claim 1 , triisopropylsilyloxymethyl (TOM) and 2′-O-bis(2-acetoxyethoxy)methyl (ACE).4. The method of claim 1 , wherein the ...

POLYENE MACROLIDE DERIVATIVE

The present invention is the following Amphotericin B derivative: 3. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein J claim 1 , L and Vare hydroxy; and Jand Vare hydrogen.4. The compound or its pharmaceutically acceptable salt according to claim 1 , wherein X is a group of formula: —N(R)—CO—X; Xis a group represented by formula (III); and T is a bond.5. The compound or its pharmaceutically acceptable salt according to claim 4 , wherein Ris halogen claim 4 , hydroxy claim 4 , carboxy claim 4 , substituted or unsubstituted amino claim 4 , substituted or unsubstituted aromatic heterocyclylamino claim 4 , substituted or unsubstituted non-aromatic heterocyclylamino claim 4 , substituted or unsubstituted alkylammonium claim 4 , carbamoyl claim 4 , sulfamoyl claim 4 , sulfo claim 4 , cyano claim 4 , substituted or unsubstituted ureido claim 4 , guanidino claim 4 , substituted or unsubstituted alkyloxy claim 4 , substituted or unsubstituted non-aromatic heterocyclyloxy claim 4 , substituted or unsubstituted alkylphosphonyl claim 4 , substituted sulfamoyl claim 4 , substituted or unsubstituted aromatic carbocyclyl claim 4 , substituted or unsubstituted non-aromatic carbocyclyl claim 4 , substituted or unsubstituted aromatic heterocyclyl or substituted or unsubstituted non-aromatic heterocyclyl;wherein said substituted or unsubstituted amino is selected from unsubstituted amino, hydroxyamino, sulfamoylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylsulfonylamino, substituted or unsubstituted non-aromatic carbocyclylcarbonylamino, substituted or unsubstituted aromatic carbocyclylcarbonylamino, substituted or unsubstituted aromatic heterocyclylcarbonylamino and substituted or unsubstituted non-aromatic heterocyclylcarbonylamino;wherein said substituted or unsubstituted ureido is selected from ureido, substituted or unsubstituted alkylureido, substituted or unsubstituted aromatic heterocyclylureido and ...

DNA-MN HYBRID PARTICLES AND METHOD OF MANUFACTURING THE SAME

This invention relates to DNA-Mn hybrid particles and a method of manufacturing the same, the method including producing a circular DNA template for replication and forming particles in which DNA and Mn are bound to each other using Mn during the synthesis of a new strand of DNA from the circular DNA template for replication using a DNA polymerase, thus promoting the activity of the DNA polymerase using the coenzyme function of Mn and broadening the range of application fields of DNA as a biomaterial. 1. A method of manufacturing DNA-Mn hybrid particles , comprising forming particles comprising DNA and Mn bound to each other using Mn during polymerization of DNA using a DNA polymerase.2. A method of manufacturing DNA-Mn hybrid particles , comprising:producing a circular DNA template for replication; andforming particles comprising DNA and Mn bound to each other using Mn during synthesis of a new strand of DNA from the circular DNA template for replication using a DNA polymerase,wherein the forming the particles is performed in a manner such that the circular DNA template for replication, the DNA polymerase and a Mn compound are added together and reacted at a predetermined temperature for a predetermined period of time.3. The method of claim 2 , wherein the particles have a spherical shape.4. The method of claim 3 , wherein each of the particles has a multilayer structure.5. The method of claim 2 , wherein the Mn promotes activity of the DNA polymerase.6. The method of claim 2 , wherein the particles are used as a material for an energy storage device.7. The method of claim 2 , wherein the particles are changed in size and shape by adjusting an amount of Mn that is used.8. The method of claim 2 , wherein the producing the circular DNA template for replication comprises:hybridizing a primer and ssDNA having base sequences enabling complementary binding to the primer at both terminals thereof and an arbitrary base sequence at a center thereof through complementary ...

PROCESSES AND INTERMEDIATES FOR PREPARING ANTI-HIV AGENTS

The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties. 2. (canceled)3. The compound of wherein each Ris independently —C(═O)aryl claim 1 , wherein —C(═O)aryl is optionally substituted with one or more (C-C)alkyl groups.4. The compound of wherein each Ris benzoyl.5. The compound of wherein each Ris independently (C-C)alkyl.6. (canceled)7. The compound of wherein each Ris independently aryl claim 1 , wherein aryl is optionally substituted with one or more (C-C)alkyl groups.956-. (canceled) This patent application claims the benefit of priority of U.S. application Ser. No. 61/488,133 filed May 19, 2011, which application is hereby incorporated by reference.International Patent Application Publication Number WO 2006/110157 and International Patent Application Publication Number WO 2006/015261 provide phosphonamidate derivatives of (2R′,5R′)-9-(3-fluoro-2,5-dihydro-5-phosphonomethoxy-2-furanyl)adenine that are reported to be useful as anti-HIV agents. Compound 13 is one such derivative.International Patent Application Publication Number WO 2010/005986 provides salt forms of compound 13 including the citrate salt (compound 14) which are also reported to be useful as anti-HIV agents.There is currently a need for improved methods for preparing certain compounds reported in International Patent Application Publication Numbers WO 2006/110157, WO 2006/015261 and WO 2010/005986. In particular, there is a need for new synthetic methods that are simpler or less expensive to carry out, that provide an increased yield, or that eliminate the use of toxic or costly reagents.The present invention provides new synthetic processes and synthetic intermediates that are useful for preparing the compound of formula 13 or salts or stereoisomers thereof. The present invention also provides new synthetic processes and synthetic intermediates that are useful for preparing additional compounds reported in ...

Process for the preparation of trivalent iron complexes with mono-, di- and polysaccharide sugards

Process for the preparation of trivalent iron complexes with mono-, di- and polysaccharide sugars, consisting of the activation of the sugar by oxidation with nascent bromine generated in situ by reaction between an alkaline or alkaline earth bromine and an alkaline hypochlorite, the complexation of the activated sugar in solution with a ferric salt dissolved in an aqueous solution, the purification of the resulting solution through ultrafiltration and finally the stabilization of the trivalent iron-sugar complex by heating at a temperature between 60° C. and 100° C. for a period between 1 and 4 hours at a pH between 9.0 and 11.0.

EXOCYLIC NITROGEN ATOM PROTECTED NUCLEOSIDE AND METHOD FOR PRODUCING AND USING THE SAME

The present invention provides nucleosides comprising a sterically hindered silyl protecting group on the exocyclic nitrogen atom of the nucleobase, oligonucleotides comprising the same, and methods for producing the same. In particular, the silyl protecting group is a sufficiently sterically hindered such that it is stable to a various oligonucleotide synthesis procedures. 2. The exocyclic amine-protected nucleoside of claim 1 , wherein said nucleobase is selected from the group consisting of cytosine claim 1 , adenine claim 1 , guanine claim 1 , 2 claim 1 ,6-diaminopurine claim 1 , and 5-methylcytosine.3. The exocyclic amine-protected nucleoside of claim 1 , wherein said silyl protecting group is stable to a borane reagent.4. The exocyclic amine-protected nucleoside of claim 1 , wherein said silyl protecting group is stable to a strongly basic condition.6. The exocyclic amine-protected nucleoside of claim 5 , wherein each of R claim 5 , R claim 5 , and Ris independently selected from the group consisting of methyl claim 5 , ethyl claim 5 , n-propyl claim 5 , tert-butyl claim 5 , neo-pentyl claim 5 , isobutyl claim 5 , and isopropyl; or two of R claim 5 , R claim 5 , and Rtogether form 9-BBN.7. The exocyclic amine-protected nucleotide of claim 1 , wherein a 5′-protecting group comprises an acid labile hydroxyl protecting group or a base labile hydroxyl protecting group.8. The exocyclic amine-protected nucleoside of claim 4 , wherein said 5′-protecting group comprises dimethoxytrityl claim 4 , trimethoxytrityl claim 4 , monomethoxytrityl claim 4 , trityl claim 4 , fluorenylmethyloxy claim 4 , 9-phenylxanthen-9-yl claim 4 , alkylcarbonate claim 4 , arylcarbonate claim 4 , or other sterically blocking protecting group.9. An oligonucleotide comprising a nucleobase having an exocyclic amine group that is protected with a silyl protecting group claim 4 , wherein said silyl protecting group is stable to reaction conditions associated with oligonucleotide synthesis.10. The ...

A Nucleoside Derivative For Use As A Drug, Particularly For The Treatment Of Chronic Lymphocytic Leukemia

We disclose nucleoside derivatives useful as drugs, particularly for the treatment of chronic lymphocytic leukemia. 1. A nucleoside derivative containing a boron cluster connected with the nucleoside structure at position 2 or 8 of purine nucleobase through a connecting group and its 5′ phosphate , thiophosphate or phosphonate derivative for use as a drug.2. A nucleoside derivative for use according to characterised in that the connecting group is defined by the formula:{'sub': 2', 'm', 'k', 'n', '1', '2', 'j', 'i', 'p', '2', 'r—', '2, '(CH)W(CC)T(CH)Q(CC)(CH)where: m, j and r are whole numbers from 0 to 3; k, n, l, i and p each have a value of 0 or 1; W, T and Q independently of one another denote O, S, C(O), S(O), S(O), Se, NR, where R denotes: H, alkyl, haloalkyl, alkoxyalkyl or aryl,'}the boron cluster is 1,2-dicarba-closo-dodecaborane (ortho-carboranyl), 1,7-dicarba-closo-dodecaborane (meta-carboranyl), 1,12-dicarba-closo-dodecaborane (para-carboranyl), 7, 8-dicarba-nido-undecaborane (nido-carboranyl), closo-dodecaborane or their derivatives substituted on a carbon or boron atom,that the nucleoside part of the agent is selected from a group containing a combination of guanine, adenine or cytosine and ribose, deoxyribose or arabinose residue.4. A nucleoside derivative for use according to claim 3 , characterised in that R3 denotes: OH or O (PO)m where m is a whole number from 0 to 3 claim 3 , and R4 and R5 respectively denote: H and OH or OH and H.5. A nucleoside derivative for use according to claim 1 , characterised in that it is a compound selected from the group encompassing:2-ethynyl-(1,12-dicarba-c/oso-dodecaboran-2-yDadenosine,8-ethynyl-(1,12-dicarba-doso-dodecaboran-2-yl)-2′ -deoxyadenosine,2-ethynyl-(1,12-dicarba-doso-dodecaboran-2-yparabinoadenosine,2-ethyl -(1,12-dicarba-c/oso-dodecaboran-2-yparabinoadenosine or phosphates thereof.6. A method for treatment or prophylaxis of neoplasms a comprising administering the nucleoside derivative of .7. A ...

COMPLEXES FOR INTRACELLULAR IMAGING

The present disclosure relates to complexes for intracellular imaging and also to methods and kits for intracellular imaging or cell labelling. Certain embodiments of the present disclosure provide a complex comprising a transition metal carbonyl compound, a conjugated bidentate ligand and a tetrazolato compound comprising a saccharide group. 149.-. (canceled)50. A complex comprising a transition metal carbonyl compound , a conjugated bidentate ligand and a tetrazolato compound comprising a saccharide group.51. The complex according to claim 50 , wherein the transition metal carbonyl compound is a Re(I) tricarbonyl compound.52. The complex according to claim 50 , wherein the conjugated bidentate ligand comprises a bidentate diimine ligand.53. The complex according to claim 50 , wherein the conjugated bidentate ligand comprises a phenanthroline or a bipyridine compound.54. The complex according to claim 50 , wherein the conjugated bidentate ligand comprises a 1 claim 50 , 10 phenanthroline compound and/or a substituted derivative thereof.5550. The complex according to claim 50 , wherein the tetrazolato compound comprises a phenyltetrazolate and/or a substituted derivative thereof.56. The complex according to claim 50 , wherein the tetrazolato compound comprises a 1 claim 50 ,2 claim 50 ,3 triazole phenyltetrazolate and/or a substituted derivative thereof.57. The complex according to claim 50 , wherein the tetrazolato compound comprises a monosaccharide group and/or a disaccharide group.58. The complex according to claim 50 , wherein the saccharide group comprises a mannopyranose group claim 50 , a glucose group or a galactose group.59. The complex according to claim 50 , wherein the saccharide group comprises a maltose group.62. An intracellular imaging agent claim 50 , the agent comprising a complex according to .63. A method of intracellular imaging of a cell claim 50 , the method comprising exposing a cell to a complex according to and imaging the complex in the ...

INFLAMMATION IMAGING AND THERAPY

An imaging agent comprising a conjugate of an oligosaccharide moiety with an imaging moiety. The oligosaccharide is Lewis A or Lewis B or a mimetic thereof, or a pharmaceutically acceptable salt or PEGylated form of Lewis A or Lewis B or its mimetics. Lewis A and Lewis B and its mimetics are also provided for use in the therapeutic treatment of inflammatory diseases, autoimmune diseases and cancer. 2. An imaging agent according to claim 1 , wherein the mimetic of Lewis A or Lewis B is Lewis A or Lewis B having one or more of the following modifications (i) to (iv) claim 1 , or a salt thereof or a PEGylated form thereof:{'sub': 1-6', '3', '1-12', '2-12', '2-12', '2', '3', '1-4', '1-4, '(i) one or more OH and/or NAc groups are independently replaced with hydrogen, halogen, Calkoxy, —NR′R″, —NR′COR″, —N(COR′)(COR″), —SR′, —COR′, —COOR′,—OC(O)R′, —OC(O)OR′, —OC(O)NR′R″, —OC(O)SR′, —OP(O)(OR′)(OR″), —OSOH, or Calkyl, Calkenyl or Calkynyl which is optionally substituted with one or more substituents selected from halogen, NH, N, CN, COOH, COO(Calkyl), OH and Calkoxy, or in the case of NAc may be replaced with OH;'}{'sub': 3', '1-12', '2-12', '2-12', '2', '3', '1-4', '1-4, '(ii) one or more hydrogen atoms are independently replaced with OH, halogen or a group selected from OR′, —NR′R″, —SR′, —COR′, —COOR′, —OC(O)R′, —OC(O)OR′, —OC(O)NR′R″, —OC(O)SR′, —OP(O)(OR′)(OR″), —OSOH, or Calkyl, Calkenyl or Calkynyl which is optionally substituted with one or more substituents selected from halogen, NH, N, CN, COOH, COO(Calkyl), OH and Calkoxy;'}(iii) one or more —O— moieties are independently replaced with —CR′R″—, —S—, —NR′— or —NR′CO—;{'sub': 1', '1', '1, '(iv) in the Glc saccharide unit, the unit —C(R)—O— is replaced with —C(R)═N— or —C(R)═CR′—;'}{'sub': 1-12', '2', '3', '1-4', '1-4, 'wherein each R′ and R″ is identical or different and is selected from hydrogen and Calkyl groups which are optionally substituted with one or more substituents selected from halogen, NH, N, CN, ...

COMPOSITIONS AND METHODS FOR BOROCARBOHYDRATE COMPLEXES

Borocarbohydrate complex containing compositions are presented that have an improved di-complex to boric acid ratio. In some embodiments, compositions are characterized by a di-complex to boric acid ratio of at least 5:1 and more typically at least 10:1 in liquid form, and at least 20:1 in dried form. In other embodiments, compositions are characterized by a minimum content of 80 wt % di-complex and a boric acid content of less than 15 wt %, and more typically less than 5 wt %. Contemplated compositions are thought to have improved biological activity and reduced content of undesired components. 1. A method of producing a composition that comprises borocarbohydrate complexes in an amount of at least 65 wt % , wherein the borocarbohydrate complexes include di-complexes and mono-complexes , wherein the composition further comprises boric acid , and wherein the di-complex and the boric acid are present in a ratio of at least 10:1 , the method comprising:selecting a molar ratio between a carbohydrate and the boric acid of at least 1.8:1;selecting a preparative scale for the reaction of at least 1000 ml; andreacting the carbohydrate with the boric acid at the ratio and the scale to thereby form the carbohydrate complexes, and optionally adding a cation to thereby form a salt of the carbohydrate complexes.2. The method of wherein the step of reacting forms the carbohydrate complexes in an amount of at least 70 wt %.3. The method of wherein the molar ratio between the carbohydrate and the boric acid is between 1.8:1 and 2.4:1.4. The method of wherein the preparative scale for the reaction is at least 5 claim 1 ,000 ml.5. The method of wherein the di-complex and the boric acid are present in a ratio of at least 15:1.6. The method of wherein the di-complex and the boric acid are present in a ratio of at least 20:1.7. The method of wherein the composition is a liquid composition.8. The method of wherein the carbohydrate is fructose.9. The method of wherein the cation is a ...

METHODS AND COMPOSITIONS FOR ADMINSTRATION OF IRON

The present invention generally relates to treatment of iron-related conditions with iron carbohydrate complexes. One aspect of the invention is a method of treatment of iron-related conditions with a single unit dosage of at least about 0.6 grams of elemental iron via an iron carbohydrate complex. The method generally employs iron carbohydrate complexes with nearly neutral pH, physiological osmolarity, and stable and non-immunogenic carbohydrate components so as to rapidly administer high single unit doses of iron intravenously to patients in need thereof. 1. A method of treating iron deficiency anemia , comprising:administering to an adult human subject having iron deficiency anemia a pharmaceutical composition comprising a polynuclear iron (III)-hydroxide 4(R)-(poly-(1→4)-O-α-D-glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate in a single dosage unit of at least about 0.6 grams of elemental iron, wherein the pharmaceutical composition is administered intravenously in about 15 minutes or less.2. The method of claim 1 , wherein the iron deficiency anemia is associated with non-dialysis dependent chronic kidney disease claim 1 , heavy uterine bleeding claim 1 , or a gastrointestinal disorder.3. The method of claim 1 , wherein administration of the pharmaceutical composition results in an increase in hemoglobin levels compared to hemoglobin levels before administration of the pharmaceutical composition.4. A method of treating functional iron deficiency comprising:administering to an adult human subject having iron deficiency anemia a pharmaceutical composition comprising a polynuclear iron (III)-hydroxide 4(R)-(poly-(1→4)-O-α-D-glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate in a single dosage unit of at least about 0.6 grams of elemental iron, wherein:the pharmaceutical composition is administered intravenously in about 15 minutes or less; andadministration of the pharmaceutical composition results in an increase in Transferrin saturation (TSAT ...

HOST-GUEST METAL ORGANIC FRAMEWORK SYSTEMS

The present invention relates to a method for producing Metal Organic Framework (MOF) having a framework that encapsulates a bio-molecule, the method comprising combining in a solution the bio-molecule and MOF precursors, wherein the bio-molecule promotes formation of the encapsulating framework. 112.-. (canceled)13. A crystalline Metal Organic Framework (MOF) having a framework that defines intrinsic cavities and encapsulates a bio-molecule , wherein the bio-molecule has a smallest dimension that is larger than the largest cavity diameter (LCD) of any intrinsic cavity of the framework.14. The MOF according to claim 13 , wherein the bio-molecule is a protein claim 13 , a nucleic acid claim 13 , an amino acid claim 13 , or a combination thereof.15. The MOF according to claim 14 , wherein the bio-molecule is a protein which is an enzyme.16. The MOF according to encapsulating from 1% wt to 32% wt bio-molecule relative to the weight of the MOF.17. The MOF according to claim 13 , wherein the LCD is between 5 Å and 500 Å.18. The MOF according to claim 13 , wherein the smallest dimension of the bio-molecule is at least 1.5 times larger than the LCD of any intrinsic cavity of the framework. The invention relates in general to host-guest Metal Organic Framework (MOF) systems. In particular, the invention relates to MOFs containing bio-molecules and methods for producing the same.MOFs are hybrid coordination structures formed by metal clusters comprising metal ions, e.g. metal ions or metal oxides, coordinated by multi-functional organic ligands. This results in the formation of one-, two- or three-dimensional structures that can be highly porous.The porosity of MOFs can be visualised as a spatial arrangement of cavities in the form of cages connected by channels. Depending on the particular choice of metal ions and organic ligands, MOFs having cavities in the form of open micro- and mesopores are available.The unique size characteristics and spatial distribution of the ...

METHODS AND COMPOSITIONS FOR ADMINISTRATION OF IRON

The present invention generally relates to treatment of iron-related conditions with iron carbohydrate complexes. One aspect of the invention is a method of treatment of iron-related conditions with a single unit dosage of at least about 0.6 grams of elemental iron via an iron carbohydrate complex. The method generally employs iron carbohydrate complexes with nearly neutral pH, physiological osmolarity, and stable and non-immunogenic carbohydrate components so as to rapidly administer high single unit doses of iron intravenously to patients in need thereof. 1. A method of treating a disease , disorder , or condition characterized by iron deficiency or dysfunctional iron metabolism , comprising intravenously administering to a subject in need thereof an iron carbohydrate complex in a single dosage unit of at least 0.7 grams of elemental iron in 15 minutes.2. The method of claim 1 , wherein the disease claim 1 , disorder claim 1 , or condition is anemia.3. The method of claim 2 , wherein the anemia is iron deficiency anemia.4. The method of claim 3 , wherein the iron deficiency anemia is associated with chronic blood loss; acute blood loss; pregnancy; childbirth; childhood development; psychomotor and cognitive development in children; breath holding spells; heavy uterine bleeding; menstruation; chronic recurrent hemoptysis; idiopathic pulmonary siderosis; chronic internal bleeding; gastrointestinal bleeding; parasitic infections; chronic kidney disease; dialysis; surgery or acute trauma; and chronic ingestion of alcohol claim 3 , chronic ingestion of salicylates claim 3 , chronic ingestion of steroids; chronic ingestion of non-steroidal anti-inflammatory agents claim 3 , or chronic ingestion of erythropoiesis stimulating agents.5. The method of claim 2 , wherein the anemia is anemia of chronic disease.6. The method of claim 5 , wherein the chronic disease is selected from the group consisting of rheumatoid arthritis; cancer; Hodgkin's leukemia; non-Hodgkin's leukemia ...

THE SCANO-miR PLATFORM IDENTIFIES A DISTINCT CIRCULATING MICRORNA SIGNATURE FOR THE DIAGNOSIS OF DISEASE

The disclosure relates to the identification of a novel molecular signature based on the differential expression of circulating microRNAs (miRNA) in serum samples specific to patients with clinically significant diseases or disorders, such as cancer. 1. A method of detecting aggressive prostate cancer in an individual , the method comprising: isolating miRNA from a sample from the individual; ligating the miRNA to a universal linker; hybridizing the miRNA to a nucleic acid that is on a surface , wherein the nucleic acid is complementary to miR-433 and/or miR-200c; contacting the miRNA with a spherical nucleic acid (SNA) , wherein the SNA comprises a polynucleotide that is sufficiently complementary to the universal linker to hybridize under appropriate conditions; wherein detection of the SNA is indicative of aggressive prostate cancer in the individual.2. The method of wherein the SNA comprises a metal.3. The method of wherein the SNA comprises gold.4. The method of wherein the SNA is hollow.5. The method of wherein the SNA comprises a liposome.6. The method of any one of - wherein the surface is an array.7. The method of wherein the array comprises a plurality of different nucleic acids.8. The method of any one of - wherein the sample is a body fluid claim 6 , serum claim 6 , or tissue obtained from an individual suffering from a disease.9. The method of any one of - wherein the sample is a liquid biopsy obtained from an individual suffering from a disease.10. The method of any one of - wherein the sample is a body fluid claim 6 , serum claim 6 , or tissue obtained from an individual not known to be suffering from a disease.11. The method of any one of - wherein the sample is a liquid biopsy obtained from an individual not known to be suffering from a disease.12. The method of or wherein the profile is compared to an earlier profile determined from the individual.13. The method of or wherein the profile is compared to a profile determined from an additional ...

COMPOSITIONS, KITS, AND METHODS TO INDUCE ACQUIRED CYTORESISTANCE USING STRESS PROTEIN INDUCERS

The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism. 1. A method of protecting an organ of a human patient from injury based on a scheduled insult comprising administering to the organ a therapeutically effective amount of (i) iron sucrose; and (ii) vitamin B12 or a derivative thereof , the therapeutically effective amount being administered before the insult to the organ occurs.2. The method of claim 1 , wherein the insult is a scheduled insult.3. The method of claim 2 , wherein the scheduled insult is surgery claim 2 , chemotherapy claim 2 , or radiocontrast toxicity.4. The method of claim 3 , wherein the surgery is an organ transplant surgery.5. The method of claim 2 , wherein the administration occurs at least 2 hours before the scheduled insult to the organ occurs.6. The method of claim 2 , wherein the administration occurs at least 4 hours before the scheduled insult to the organ occurs.7. The method of claim 2 , wherein the administration occurs at least 12 hours before the scheduled insult to the organ occurs.8. The method of claim 2 , wherein the administration occurs at least 18 hours before the scheduled insult to the organ occurs.9. The method of claim 1 , wherein the organ is a transplanted organ.10. The method of claim 1 , wherein the organ is a heart claim 1 , kidney claim 1 , liver claim 1 , or lung.11. The method of claim 1 , wherein the organ is a kidney and protection is evidenced by prevention or reduction in BUN or serum creatinine increases as compared to a reference level.12. A method of protecting an organ of a human patient from injury based on a scheduled insult comprising administering to the organ a therapeutically effective amount of (i) iron sucrose; and (ii) vitamin B12 or a derivative thereof ...

METHOD OF PREPARING NUCLEASE-RESISTANT DNA-INORGANIC HYBRID NANOFLOWERS

The present invention relates to a method of preparing nucleic acid-inorganic hybrid nanoflowers, which comprises allowing a nucleic acid to react with a solution of a metal ion-containing compound at room temperature, thereby forming a complex between the metal ion and the nitrogen atom of an amide bond or amine group present in the nucleic acid. According to the present invention, organic-inorganic hybrid nanoflower structures may be synthesized using nucleic acid in a simple manner under an environmentally friendly condition without any toxic chemical substance. The produced organic-inorganic hybrid nanoflower structures show a high DNA encapsulation yield, have resistance against nuclease, and show significantly increased peroxidase activity. Thus, these nanoflower structures may be widely used as a gene therapy carrier and in biosensing technology. 1. A method of preparing a nucleic acid-magnetic nanoparticles-inorganic hybrid nanoflower comprising:(a) reacting nucleic acid and amine-coated magnetic nanoparticles at room temperature to obtain a nucleic acid-magnetic nanoparticle complex bound by electrostatic attraction; and(b) obtaining a nucleic acid-magnetic nanoparticles-inorganic hybrid nanoflower by reacting a solution in which a metal ion-containing compound is dissolved and the nucleic acid-magnetic nanoparticle complex at room temperature to induce a covalent coordination bond between amide bond present in the nucleic acid or nitrogen atom in amine group and nitrogen atom present in amine group and a metal ion on surface of the magnetic nanoparticles.2. The method of preparing nucleic acid-magnetic nanoparticles-inorganic hybrid nanoflower of claim 1 , wherein the nucleic acid is DNA or RNA.3. The method of preparing nucleic acid-magnetic nanoparticles-inorganic hybrid nanoflower of claim 1 , wherein the metal is at least one selected from the group consisting of copper (Cu) claim 1 , zinc (Zn) claim 1 , calcium (Ca) and manganese (Mn).4. The method of ...

Beta-D-2'-DEOXY-2'-alpha-FLUORO-2'-beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: This application claims priority to U.S. Ser. No. 62/129,319 filed on Mar. 6, 2015, U.S. Ser. No. 62/253,958 filed on Nov. 11, 2015, and U.S. Ser. No. 62/276,597 filed on Jan. 8, 2016, each of which is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof to treat the Hepatitis C virus (“HCV”).Hepatitis C (HCV) is an RNA single stranded virus and member of the Hepacivirus genus. It is estimated that 75% of all cases of liver disease are caused by HCV. HCV infection can lead to cirrhosis and liver cancer, and if left to progress, liver failure which may require a liver transplant. Approximately 170-200 million people worldwide are infected, with an estimated 3-4 million infections in the United States.RNA polymerase is a key component in the targeting of RNA single stranded viruses. The HCV non-structural protein NS5B RNA-dependent RNA polymerase is a key enzyme responsible for initiating and catalyzing viral RNA synthesis. As a result, HCV NS5B is an attractive target for the current drug discovery and development of anti-HCV agents. There are two major subclasses of NS5B inhibitors: nucleoside analogs, which are anabolized to their active triphosphates—which act as alternative substrates for the polymerase—and non-nucleoside inhibitors (NNIs), which bind to allosteric regions on the protein. Nucleoside or nucleotide inhibitors mimic natural polymerase substrate and act as chain terminators. They inhibit the initiation of RNA transcription and elongation of a nascent RNA chain.In addition to targeting RNA polymerase, other RNA viral proteins may also be targeted in combination therapies. For example, HCV proteins that are additional targets for therapeutic approaches are NS3/4A (a serine protease) and NS5A (a non-structural protein that is an essential component of HCV replicase and exerts a range of effects on cellular pathways).In December 2013, the first ...

Transcriptome In Vivo Analysis (TIVA) and Transcriptome In Situ Analysis (TISA)

Compositions and methods of capturing one or more nucleic acid molecules of a cell or subcellular compartment are described. In certain aspects, the compositions comprise a caged molecule comprising one or more photolinkers and an antisense oligonucleotide, which when uncaged hybridizes to a target nucleic acid molecule. 2. The molecule of further comprising a label for isolating nucleic acids.3. The molecule of claim 1 , further comprising a cell penetrating domain.4. The molecule of claim 1 , wherein the antisense oligonucleotide is at least an 18mer 2′fluoro oligonucleotide having a nucleic acid sequence that is substantially complementary to the polyA tail of an mRNA.5. The molecule of claim 1 , wherein the molecule is a circular caged molecule wherein a first end of the antisense oligonucleotide is directly or indirectly linked to a first photolabile ligand of the ruthenium-based photolinker and a second end of the antisense oligonucleotide is directly or indirectly linked elsewhere on the compound.6. The molecule of claim 5 , wherein the second end of the antisense oligonucleotide is directly or indirectly linked to a second photolabile ligand of the ruthenium-based photolinker.7. The molecule of claim 1 , further comprising one or more fluorophores.8. The molecule of claim 7 , wherein the one or more fluorophores is a FRET pair.9. The molecule of claim 1 , wherein the antisense oligonucleotide comprises a randomized nucleotide sequence.10. The molecule of claim 1 , wherein irradiation of ruthenium-based photolinker exposes the antisense oligonucleotide thereby allowing the antisense oligonucleotide to hybridize with a nucleic acid.11. The molecule of claim 1 , wherein the molecule is a hairpin caged molecule comprising a stem and a loop claim 1 , wherein the molecule comprises a first stem-forming oligonucleotide and a second stem-forming oligonucleotide claim 1 , wherein the first stem-forming oligonucleotide and a second stem-forming oligonucleotide ...

USE OF FLUORINE-CONTAINING WATER SOLUBLE PLATINUM COMPLEX IN PREPARING DRUGS FOR PREVENTION AND TREATMENT OF CANCERS

Disclosed in the present invention is the use of a fluorine-containing in preparing drugs for the prevention and treatment of tumors, said platinum complex being shown as formula (I). Experiments have demonstrated that the present fluorine-containing water soluble platinum complex is highly water soluble and exhibiting superior cytotoxicity and efficacy compare to the clinical platinum drugs. Said complex alone or in combination with other chemotherapeutics is able to treat cancer in mammals, and in particular, humans, said cancers including lung cancer, colon cancer, head and neck cancer, prostate cancer, breast cancer, ovarian cancer, cervical cancer, leukemia, lymphoid cancer, skin cancer, pancreatic cancer, liver cancer, bladder cancer, esophageal cancer, gastric cancer, male genital cancer or bone cancer. 110-. (canceled)13. The method for treating and preventing cancer with the platinum complex of claim 11 , wherein X and Y together form trans-(1R claim 11 ,2R)-cyclohexanediamine;15. The method of claim 14 , wherein wherein X and Y together form trans-(1R claim 14 ,2R)-cyclohexanediamine;16. The method of claim 14 , wherein the further chemotherapeutic agent is one or more members selected from 5-FU and Folinic Acid. Certain aspects of the present disclosure provide a method of preventing and treating cancer, especially involving the methods of using fluorine-containing water-soluble platinum complexes for prevention and treatment of cancer.Cancer is a disease that gene mutation under certain circumstances leads to uncontrolled cell division, thus resulting in continually growth and metastasis of the cell to kill the host. The drugs of prevention and treatment of cancer include alkylating agents, antagonists of cell metabolism, antitumor antibiotics, alkaloids, platinum complexes, as well as asparaginase inhibitors and hormonal therapy and the like. The main purpose of almost all of the antitum.or drugs is to effectively prevent the rapid cell division in a ...

Ruthenium-Based Photolinkers and Methods of Use

The present invention provides ruthenium-based photolinker compounds, caged molecules comprising the ruthenium-based photolinker compounds, and methods of use. In certain aspects, the compositions disclosed herein comprise an active domain conjugated to a ruthenium-based photolinker, such that irradiation of the photolinker exposes the active domain. 2. The composition of claim 1 , wherein Xand Xare each independently selected from the group consisting of 3-ethynylpyridine claim 1 , 3-(bromomethyl)pyridine claim 1 , maleimide claim 1 , nicotinaldehyde claim 1 , 1-(4-(pyridin-3-yl)-1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)ethanone claim 1 , 4-pentynenitrile claim 1 , and 4-aminobutyne.3. The composition of claim 1 , wherein Land Lare joined to form a first bidentate ligand and Land Lare joined to form a second bidentate ligand claim 1 , further wherein the first bidentate ligand and the second bidentate ligand are selected from the group consisting of 2 claim 1 ,2′-bipyridyl (bpy) and biquinoline.4. The composition of claim 1 , wherein L claim 1 , L claim 1 , and Lare joined to form a tridentate ligand claim 1 , further wherein the tridentate ligand is 2 claim 1 ,2′:6′ claim 1 ,2″-terpyridine.5. The composition of claim 4 , wherein Lis a fluorophore.6. The composition of claim 1 , wherein the compound of formula (II) is selected from the group consisting of [Ru(bipyridine)(3-ethynyl-pyridine)] claim 1 , Ru(bipyridine)(3-ethynylpyridine)Cl claim 1 , Ru(bipyridine)(3-ethynylpyridine)(PF) claim 1 , [Ru(biquinoline)(4-pentynenitrile)] claim 1 , Ru(biquinoline)(4-pentynenitrile)Cl claim 1 , Ru(biquinoline)(4-pentynenitrile)(PF) claim 1 , [Ru(bipyridine)(4-aminobutyne)] claim 1 , [Ru(bipyridine)(4-pentynenitrile)] claim 1 , [Ru(bipyridine)(nicotinaldehyde)] claim 1 , [Ru(bipyridine)(1-(4-(pyridin-3-yl)-1H-1 claim 1 ,2 claim 1 ,3-triazol-1-yl)ethanone)] claim 1 , [Ru(bipyridine)(3-(bromomethyl)pyridine)]2+ claim 1 , [Ru(bipyridine)(maleimide)] claim 1 , a salt thereof claim ...

COMPOSITIONS, KITS, AND METHODS TO INDUCE ACQUIRED CYTORESISTANCE USING STRESS PROTEIN INDUCERS

The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism. 1244.-. (canceled)246. A kit comprising: a therapeutically effective amount of: (i) iron sucrose and (ii) tin protoporphyrin , wherein administration of the therapeutically effective amount of the iron sucrose and the tin protoporphyrin to an organ at least one of: protects the organ without causing injury to the organ; generates acquired cytoresistance in the organ in the absence of causing injury to the organ; or up-regulates expression of protective stress proteins in the organ without causing injury to the organ.247. A kit of claim 246 , further comprising administration instructions.248. A kit of claim 246 , wherein the organ is protected from an injury based on an insult.249. A kit of claim 246 , wherein the administration occurs at least 8 hours before a scheduled insult.250. A kit of claim 249 , wherein the scheduled insult is surgery claim 249 , chemotherapy claim 249 , or radiocontrast toxicity.251. A kit of claim 250 , wherein the surgery is an organ transplant surgery.252. A kit of claim 246 , wherein the organ is a transplanted organ.253. A kit of claim 246 , wherein the organ is a kidney and protection against injury is evidenced by prevention or reduction in blood urea nitrogen (BUN) or serum creatinine increases as compared to a reference level.254. A kit of claim 246 , wherein the kit includes a therapeutically effective amount of vitamin B12 or a derivative of vitamin B12.255. A kit of claim 246 , wherein the kit includes a therapeutically effective amount of myoglobin or a nitrited myoglobin.256. A method comprising administering to an organ a composition comprising a therapeutically effective amount of: (i) iron sucrose and (ii) tin protoporphyrin claim ...