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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 16172. Отображено 100.
10-11-2014 дата публикации

СЕНСОР ДЛЯ АНАЛИЗА ГЛИЦИНА В ВОДНЫХ РАСТВОРАХ

Номер: RU0000147538U1

Сенсор для определения глицина в водной среде, включающий серебряную поверхность кварцевого резонатора, отличающийся тем, что поверхность модифицирована сульфидом серебра. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 147 538 U1 (51) МПК G01N 31/00 (2006.01) G01N 27/00 (2006.01) C07C 229/08 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ (21)(22) Заявка: ПОЛЕЗНОЙ МОДЕЛИ К ПАТЕНТУ 2014126453/15, 30.06.2014 (24) Дата начала отсчета срока действия патента: 30.06.2014 (45) Опубликовано: 10.11.2014 Бюл. № 31 (54) СЕНСОР ДЛЯ АНАЛИЗА ГЛИЦИНА В ВОДНЫХ РАСТВОРАХ Формула полезной модели Сенсор для определения глицина в водной среде, включающий серебряную поверхность кварцевого резонатора, отличающийся тем, что поверхность модифицирована сульфидом серебра. 1 4 7 5 3 8 Адрес для переписки: 170100, г. Тверь, ул. Желябова, 33, Тверской государственный университет, Управление интеллектуальной собственности (73) Патентообладатель(и): Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Тверской государственный университет" (RU) R U Приоритет(ы): (22) Дата подачи заявки: 30.06.2014 (72) Автор(ы): Рясенский Сергей Станиславович (RU), Феофанова Мариана Александровна (RU), Скобин Михаил Игоревич (RU), Мельников Никита Валерьевич (RU) R U 1 4 7 5 3 8 U 1 U 1 Стр.: 1 RU 5 10 15 20 25 30 35 40 45 147 538 U1 Сенсор для анализа глицина в водных растворах относится к области аналитической химии и может быть использован в химической, микробиологической, фармацевтической промышленности. В качестве ближайшего аналога (прототипа) выбран акустический сенсор для определения глицина и глицил - глицина в водных и спиртовых растворах (В.Ф. Селеменев, А.Н. Зяблов, А.В. Калач. Определение глицина и глицил-глицина в водных и спиртовых растворах с использованием акустического сенсора // Журн. Заводская лаборатория. Диагностика материалов. 2007. №7, т. 73. С. 17-20), состоящий из стеклянного корпуса с подвижным стеклянным колпачком, ...

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26-01-2012 дата публикации

Compositions and methods for the treatment of pathological condition(s) related to gpr35 and/or gpr35-herg complex

Номер: US20120022116A1
Принадлежит: Corning Inc

Disclosed are compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically related to GPR35, and/or GPR35-hERG signaling complex. For example, disclosed are compounds for preventing and/or treating diseases which are pathophysiologically related to GPR35 in a subject. The compounds having a formula (I), (II) or (III):

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26-01-2012 дата публикации

Process for the production of carnitine from beta-lactones

Номер: US20120022288A1
Принадлежит: Lonza AG

The invention relates to a method for the production of L-carnitine, wherein a β-lactone, which is a 4-(halomethyl)oxetane-2-one, is converted into carnitine with trimethylamine (TMA), wherein the β-lactone is not subjected to a basic hydrolysis step before being contacted with the trimethylamine. The invention also relates to a carnitine having a unique impurity profile.

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02-02-2012 дата публикации

Novel lipids and compositions for the delivery of therapeutics

Номер: US20120027796A1
Принадлежит: Alnylam Pharmaceuticals Inc

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structures: (Formula (I) or (XXXV)).

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09-02-2012 дата публикации

Plasmalogen compounds, pharmaceutical compositions containing the same and methods for treating diseases of the aging

Номер: US20120035250A1
Принадлежит: Phenomenome Discoveries Inc

Described herein are routes of synthesis and therapeutic uses of 1-alkyl, 2-acyl glycerol derivatives of formula I: which when administered to mammalian biological systems result in increased cellular concentrations of specific sn-2 substituted ethanolamine plasmalogens independent of the ether lipid synthesis capacity of the system. Elevating levels of the specific sn-2 substituted species in this way can cause lowering of membrane cholesterol levels and the lowering of amyloid secretion. These compounds can be used for the treatment or prevention of diseases of aging associated with increased membrane cholesterol, increased amyloid, and decreased plasmalogen levels, such as neurodegeneration (including Alzheimer's disease, Parkinson's disease and age-related macular degeneration), cognitive impairment, dementia, cancer (e.g. prostate, lung, breast, ovarian, and kidney cancers), osteoporosis, bipolar disorder and vascular diseases (such as atherosclerosis, hypercholesterolemia).

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23-02-2012 дата публикации

Intermediates in the enantioselective synthesis of 3-(aminomethyl)-5-methyl-hexanoic acid

Номер: US20120046468A1

(S)-(+)-3-(aminomethyl)-5-methyl-hexanoic acid or (S)-pregabalin is an anticonvulsive drug. In addition to its use as an anticonvulsive agent, pregabalin has also been indicated as a medicament in the treatment of anxiety, neuropathic pain and pain in patients with fibromyalgia. Provided herein are thioester intermediates in the synthesis of and processes for the synthesis of 3-(aminomethyl)-5-methyl-hexanoic acid in the (R) or (S) configuration.

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23-02-2012 дата публикации

Method of preparing an alkylamine derivative

Номер: US20120046494A1
Принадлежит: Kolon Life Science Inc

The present invention provides a method of preparing an alkylamine derivates which hardly generates impurities and enables mass production with high purity.

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29-03-2012 дата публикации

Process for producing granules comprising one or more complexing agent salts

Номер: US20120077727A1
Принадлежит: BASF SE

A process for producing granules containing one or more complexing agent salts of the general formula from an aqueous starting solution, containing the one or more complexing agent salts in a concentration of from 10 to 80% by weight, based on the total weight of the aqueous starting solution, in a jet apparatus.

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12-04-2012 дата публикации

Acetylsalicylic acid salts

Номер: US20120088742A1
Принадлежит: Tetra Sia

Novel betaine salts of acetylsalicylic acid, namely 4-trimethylammoniobutanoate acetylsalicylic acid addition salt (gamma-butyrobetaine acetylsalicylate), L-carnitine acetylsalicylic acid addition salt and 3-(trimethylammonioamino)propanoate (meldonium) acetylsalicylic acid addition salt. Use of meldonium acetylsalicylate as antiplatelet agent for treating various pathologies induced by platelet aggregation, anti-inflammatory and antihyperlipidemic agent.

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19-04-2012 дата публикации

Novel lipids and compositions for the delivery of therapeutics

Номер: US20120095075A1
Принадлежит: Alnylam Pharmaceuticals Inc

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure:

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10-05-2012 дата публикации

Bismuth-containing compounds, coordination polymers, methods for modulating pharmacokinetic properties of biologically active agents, and methods for treating patients

Номер: US20120115823A1
Принадлежит: Synthonics Inc

Bismuth-containing compounds include bismuth and a biologically active agent coordinated to the bismuth. The biologically active agent includes at least one heteroatom configured for coordination with the bismuth. Coordination polymers include a polymer matrix that contains a bismuth-containing compound. Methods for modulating a pharmacokinetic property of a biologically active agent include coordinating the biologically active agent to bismuth to form a bismuth-containing compound, and administering the bismuth-containing compound orally to a patient. Methods for treating Parkinson's disease, methods for treating hypothyroidism, methods for treating ulcerative colitis, and methods for treating cancer each include administering a bismuth-containing compound to a patient.

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10-05-2012 дата публикации

Esters with Antimicrobial, Bioresistant and Fungal Resistant Properties

Номер: US20120116115A1
Автор: Thomas Daly
Принадлежит: Individual

A bromine/nitro moiety linked into the backbone of an ester or other compound over a wide range of occurrence rates provides antimicrobial, bio-resistant and fungal resistant properties for metal working fluids (MWF)s and other coatings. The moiety can be have the bromo and nitro groups linked to the same or different carbon atoms. The present invention also relates to urethanes, urea, amides, imides, carbonates, ethers, siloxanes, and many other types of linkages essential to MWF bases.

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17-05-2012 дата публикации

No-Carrier-Added Nucleophilic [F-18] Fluorination of Aromatic Compounds

Номер: US20120123120A1
Принадлежит: UNIVERSITY OF CALIFORNIA

Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No-carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F-18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F-18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F-18]fluoro-L-dopa.

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07-06-2012 дата публикации

Compositions and methods relating to proliferative diseases

Номер: US20120141578A1
Принадлежит: PENN STATE RESEARCH FOUNDATION

Anti-cancer compositions and methods are described herein. In particular, compositions including one or more of leelamine, a leelamine derivative, abietylamine, an abietylamine derivative, and an abietic acid derivative are described. Methods for treatment of pathological conditions particularly cancer, in a subject using one or more of leelamine, a leelamine derivative, abietylamine, an abietylamine derivative, and an abietic acid derivative are described herein.

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07-06-2012 дата публикации

Process for preparing pregabalin

Номер: US20120142949A1
Автор: B. S. Pradhan
Принадлежит: HELVETICA IND (P) Ltd

The invention relates to a process for preparing a compound of formula (I): wherein said process comprises hydrogenation of a compound of formula (II); under alkaline conditions, wherein R represents hydrogen or a labile group capable of being converted to hydrogen. The invention also relates to intermediates used in said process, to the use of said intermediates in the preparation of pregabalin and to a process for resolving racemic compounds of formula (I).

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07-06-2012 дата публикации

Process to prepare a chelating agent or precursor thereof using a cyanide salt

Номер: US20120142964A1
Принадлежит: Akzo Nobel Chemicals International BV

The present invention relates to a process comprising the reaction of a cyanide with an amino acid and an aldehyde, characterized in that the cyanide is a cyanide salt, the amino acid is aspartic acid and/or glutamic acid in the acidic form, and the process is performed under acidic pH by the addition of between 0 and 1 equivalent of an acid based on the amount of aspartic or glutamic acid.

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28-06-2012 дата публикации

Nano-sized particles comprising multi-headed amphiphiles for targeted drug delivery

Номер: US20120164072A1

Nano-sized particles are provided comprising at least one multi-headed amphiphilic compound, in which at least one headgroup of said multi-headed amphiphilic compound is selectively cleavable or contains a selectively cleavable group, and at least one biologically active agent, which is both encapsulated within the nano-particle and non-covalently associated thereto.

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05-07-2012 дата публикации

Compositions, Synthesis, and Methods of Using Cycloalkylmethylamine Derivatives

Номер: US20120172426A1
Принадлежит: Reviva Pharmaceuticals Inc

The present invention provides novel cycloalkylmethylamine derivatives, and methods of preparing cycloalkylmethylamine derivatives. The present invention also provides methods of using cycloalkylmethylamine derivatives and compositions of cycloalkylmethylamine derivatives. The pharmaceutical compositions of the compounds of the present invention can be advantageously used for treating and/or preventing obesity and obesity related co-morbid indications and depression and depression related co-morbid indications.

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26-07-2012 дата публикации

Michael addition reaction product and active energy ray-curable composition

Номер: US20120190846A1
Принадлежит: DIC Corp

The present invention provides a Michael addition reaction product between a specified compound having a group which functions as a Michael donor and a monomer or polymer having a group which functions as a Michael acceptor, a photoinitiator containing the Michael addition reaction product, and an active energy ray-curable composition containing the photoinitiator. The compound having a group functioning as a Michael donor used in the present invention is a phenyl ketone derivative and is characterized by having an amino group or a mercapto group as the group functioning as a Michael donor.

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09-08-2012 дата публикации

Process for the preparation of a powder comprising one or more complexing agent salts

Номер: US20120202731A1
Принадлежит: BASF SE

A process is proposed for the preparation of a powder comprising one or more complexing agent salts of the general formula starting from an aqueous solution comprising the one or more complexing agent salts in a concentration of from 10 to 80% by weight, based on the total weight of the aqueous solution, in a spray-drying process, comprising an atomization step and a drying step, wherein the atomization step is carried out with the addition of crystalline fine dust of the same complexing agent salt(s) as are present in the aqueous solution, or one or more complexing agent salts different therefrom, with an upper limit for the average particle diameter of the crystalline fine dust which is lower by at least a factor of 2 than the lower limit of the average particle diameter of the powder obtained after the process, in a fraction of from 0.1 to 20% by weight, based on the weight of the powder obtained after the process.

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09-08-2012 дата публикации

Substituted 4-aminocyclohexane derivatives

Номер: US20120202810A1
Принадлежит: GRUENENTHAL GmbH

The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain and other conditions.

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16-08-2012 дата публикации

L-ornithine phenyl acetate and methods of making thereof

Номер: US20120208885A1
Принадлежит: Ocera Therapeutics Inc

Disclosed herein are forms of L-ornithine phenyl acetate and methods of making the same. A crystalline form may, in some embodiments, be Forms I, II, III and V, or mixtures thereof. The crystalline forms may be formulated for treating subjects with liver disorders, such as hepatic encephalopathy. Accordingly, some embodiments include formulations and methods of administering L-ornithine phenyl acetate.

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30-08-2012 дата публикации

Process for reduction of alpha-acyloxy sulfide derivatives

Номер: US20120220784A1
Принадлежит: Scinopharm Singapore Pte Ltd

The present invention provides an efficient and scalable process to prepare the compound of formula 4 by reduction of the corresponding α-acyloxy sulfides.

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06-09-2012 дата публикации

Compositions and methods useful for treating diseases

Номер: US20120225851A1
Принадлежит: Eutropics Pharmaceuticals Inc

The present invention relates to a chemotherapeutic cancer treatment in which compounds of Formula Ia′, Ib′, Ic′, or II′ (referred to as a group as BH3Is) are administered to a mammal for the treatment of B-cell Lymphoma or other hematopoietic cancers, including diseases associated with MCL-1. In another aspect, the invention provides a method for treating particular types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more compounds selected from the group consisting of compounds or Formula Ia, Ib, Ic, or II in combination with other therapies, for example, a class of therapeutics known as 26S proteosome inhibitors, such as, for example, Bortezomib. In another aspect the present invention relates to autoimmune treatment with pharmaceutical compositions comprising one or more compounds of Formula Ia′, Ib′, Ic′, or II′. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.

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11-10-2012 дата публикации

Novel ligands that modulate rar receptors

Номер: US20120258996A1
Принадлежит: Galderma Research and Development SNC

Novel ligand compounds having the general formula (I): and pharmaceutical/cosmetic compositions comprised thereof are useful in human and veterinary medicine or, alternatively, in cosmetics.

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18-10-2012 дата публикации

Salt forms of [R-(R*,R*)]-2-(4-flurorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid

Номер: US20120264934A1
Принадлежит: PFIZER INC

Novel salt forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid characterized by their X-ray powder diffraction pattern and solid-state NMR spectra are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia, and Alzheimer's Disease.

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18-10-2012 дата публикации

Biological Buffers with Wide Buffering Ranges

Номер: US20120264945A1
Автор: Thomas Daly
Принадлежит: Thomas Daly

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.

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25-10-2012 дата публикации

Small molecules that covalently modify transthyretin

Номер: US20120270938A1
Принадлежит: Scripps Research Institute

A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

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15-11-2012 дата публикации

Novel compounds with high therapeutic index

Номер: US20120289471A1
Автор: V. Ravi Chandran
Принадлежит: Signature R&D Holdings LLC

The present invention is directed to novel therapeutic compounds comprised of an amino acid bonded to a medicament or drug having a hydroxy, amino, carboxy or acylating derivative thereon. These high therapeutic index derivatives have the same utility as the drug from which they are made, and they have enhanced pharmacological and pharmaceutical properties. In fact, the novel drug derivatives of the present invention enhance at least one therapeutic quality, as defined herein. The present invention is also directed to pharmaceutical compositions containing same.

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13-12-2012 дата публикации

METHOD OF RESOLUTION OF (RS)- 1,1'-BI-2-NAPHTHOL FOR OBTAINING ENANTIOMERIC PURE I.E. (S)-(-)-1,1'-BI-2-NAPHTHOL AND/OR (R)-(+)-1,1'-BI-2-NAPHTHOL VIA CO-CRYSTAL FORMATION WITH OPTICALLY ACTIVE DERIVATIVES OF y -AMINO ACIDS

Номер: US20120316361A1
Принадлежит: Lupin Ltd

Novel method for synthesis of optically pure (S)-(−)-1,1′-bi-2-naphthol and/or (R)-(+)-1,1′-bi-2-naphthol via resolution of racemic (RS)-1,1′-bi-2-naphthol through formation of co-crystal with optically active derivatives of γ-amino acids.

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20-12-2012 дата публикации

Development of Novel Detergents for Use in PCR Systems

Номер: US20120322066A1
Принадлежит: Life Technologies Corp

This disclosure relates to novel detergents for use in various procedures including, for example, nucleic acid amplification reactions such as polymerase chain reaction (PCR). Methods for preparing the modified detergents are also described.

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10-01-2013 дата публикации

Synergists

Номер: US20130012611A1
Принадлежит: SUN CHEMICAL BV

Compounds of formula (I): wherein Ar represents an, optionally substituted, aryl or heteroaryl group, R represents an, optionally substituted, aryl or heteroaryl group, an optionally substituted straight or branched chain C 1.10 -alkyl, R 1 is H or methyl, X is an extender group, n is 0 or an integer between 1 and 12 inclusive, A is a polyol residue wherein the unsubstituted polyol from which the residue is derived has at least y OH groups, and y is an integer>1, can easily be prepared, and are useful as synergists in radiation curing.

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07-02-2013 дата публикации

Pyrrolysine analogs

Номер: US20130035478A1
Принадлежит: Ohio State University

Several different pyrrolysine analogs are disclosed in this application. Those analogs have distinct chemical and biophysical properties. Some analogs are useful in chemical ligation applications. Methods of making and using are also disclosed.

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28-02-2013 дата публикации

Method for producing a solid with sufficiently low hygroscopicity which comprises glutamic acid-n,n-diacetic acid (glda) or a derivative thereof

Номер: US20130053296A1
Автор: Andreas Baranyai
Принадлежит: BASF SE

The present invention relates to a solid with sufficiently low hygroscopicity which comprises glutamic acid-N,N-diacetic acid (GLDA) or derivatives and/or salts thereof, and a method for its production.

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28-02-2013 дата публикации

2,5-di(methoxyanilino) terephthalic acid polymorphs and quinacridones realized therefrom2,5-di(methoxyanilino) terephthalic acid polymorphs and quinacridones realized therefrom

Номер: US20130053568A1
Принадлежит: Individual

2,5-di(p-methoxyanilino)terephthalic acid crystal types I and II are made by controlling the pH during the recovery of the oxidized product of the condensation of dimethylsuccinyl succinate with p-methoxyaniline. The resulting 2,5-di(p-methoxyanilino)-terephthalic acid can be converted into 2,9-dimethoxyquinacridone or a solid solution thereof having controlled characteristics.

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21-03-2013 дата публикации

Process for Making Modulators of Cystic Fibrosis Transmembrane Conductance Regulator

Номер: US20130072522A1
Принадлежит: Vertex Pharmaceuticals Inc

The invention provides a process for the preparation of a compound of Formula 1, comprising coupling a carboxylic acid of Formula 2 with an aniline of Formula 3 in the presence of a coupling agent.

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21-03-2013 дата публикации

Dispersant composition

Номер: US20130072703A1
Принадлежит: Lubrizol Advanced Materials Inc

The present invention relates to a composition containing a particulate solid, a non-polar organic medium, and a compound obtained/obtainable by reacting an aromatic amine with hydrocarbyl-substituted acylating agent, wherein the hydrocarbyl-substituted acylating agent is selected from the group consisting of an oligomer or polymer from condensation polymerisation of a hydroxy-substituted C 10-30 carboxylic acid into a polyester, an optionally hydroxy-substituted C 10-30 carboxylic acid, a C 10-30 -hydrocarbyl substituted acylating agent, and a polyolefin-substituted maleic anhydride. The invention further provides compositions for inks, thermoplastics, plasticisers, plastisols, crude grinding and flush.

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21-03-2013 дата публикации

DISPERSANT COMPOSITION

Номер: US20130072704A1
Принадлежит: LUBRIZOL ADVANCED MATERIALS, INC.

The present invention relates to a composition containing a particulate solid, a non-polar organic medium, and a compound obtained/obtainable by reacting an aromatic amine with hydrocarbyl-substituted acylating agent, wherein the hydrocarbyl-substituted acylating agent is selected from the group consisting of an oligomer or polymer from condensation polymerisation of a hydroxy-substituted Ccarboxylic acid into a polyester, an optionally hydroxy-substituted Ccarboxylic acid, a C-hydrocarbyl substituted acylating agent, and a polyolefin-substituted maleic anhydride. The invention further provides compositions for inks, thermoplastics, plasticisers, plastisols, crude grinding and flush. 129-. (canceled)31. The compound of claim 30 , wherein the aromatic amine to hydro-carbyl-substituted acylating agent mole ratio may be in the range of 2:1 to 1:10.32. The compound of claim 30 , wherein the aromatic amine to hydro-carbyl-substituted acylating agent mole ratio may be 1:1 to 1:2.33. The compound of claim 30 , wherein the compound is obtained by reacting an aromatic amine with a hydroxy-substituted Ccarboxylic acid claim 30 , or mixtures thereof.34. The compound of claim 30 , wherein the hydroxy-substituted Ccarboxylic acid is polymerised to form a polyester.35. The composition of claim 34 , wherein the polyester is a polymerisation product of a hydroxy-substituted carboxylic acid of general formula HO—X—COOH claim 34 , wherein X is a divalent saturated or unsaturated aliphatic radical containing at least 4 carbon atoms between the hydroxyl and carboxylic acid groups.36. The compound of claim 34 , wherein the polyester has 4 to 20 repeat units of a hydroxy-substituted Ccarboxylic acid.37. The compound of claim 33 , wherein the hydroxy-substituted Ccarboxylic acid is a mixture of ricinoleic acid and either 12-hydroxystearic acid or 9- and 10-hydroxystearic acids.38. The compound of claim 33 , wherein the hydroxy-substituted Ccarboxylic acid is ricinoleic acid claim 33 , 12- ...

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28-03-2013 дата публикации

NOVEL DERIVATIVES OF MESALAZINE, PROCESS OF THEIR PREPARATION AND THEIR USE IN THE TREATMENT OF INTESTINAL INFLAMMATORY DISEASES

Номер: US20130079399A1
Автор: LABRUZZO Carla
Принадлежит: SOFAR SPA

The present invention refers to the compounds corresponding to the following general formula (I): 3. 5-amino-2-(butyryloxy)benzoic acid and/or pharmaceutically acceptable salts thereof , preferably hydrochloride salt.4. Method for treating acute or chronic intestinal inflammatory diseases claim 1 , comprising the administration to a patient in need of such treatment a compound according to claim 1 , wherein said acute or chronic intestinal inflammatory diseases are preferably selected from among IBD claim 1 , IBS claim 1 , ulcerative colitis claim 1 , Crohn's disease claim 1 , diverticular disease claim 1 , more preferably IBD.5. Method for treating according to claim 4 , wherein said acute or chronic intestinal inflammatory diseases are acute intestinal inflammatory diseases.6. Method for treating according to claim 4 , wherein said acute or chronic intestinal inflammatory diseases are chronic intestinal inflammatory diseases.7. Method for treating according to claim 6 , wherein said chronic intestinal inflammatory diseases are in a remission phase.8. A compound according to claim 2 , characterised in that it is administered enterally claim 2 , preferably orally and/or rectally claim 2 , or topically claim 2 , preferably through anal application.9. Pharmaceutical composition containing a compound according to claim 2 , and at least one physiologically acceptable excipient.10. Pharmaceutical composition according to selected from among tablet claim 9 , capsule claim 9 , granule claim 9 , microgranule claim 9 , suspension or aqueous solution claim 9 , enema claim 9 , suppository claim 9 , gel and rectal foam.13. Process according to claim 11 , wherein the step a) is conducted in an aprotic polar solvent and/or in a mixture of said solvent with HO preferably in a molar ratio comprised between 1:1 and 3:1 claim 11 , more preferably 2:1.14. Process according to claim 11 , wherein said mixture is constituted by dioxane and water claim 11 , preferably in a 2:1 molar ratio ...

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18-04-2013 дата публикации

Creatine beta-alaninate: a novel salt for increasing athletic performance

Номер: US20130096193A1
Автор: Bruce W. Kneller
Принадлежит: Individual

Disclosed are creatine β-alaninate, compositions and formulations containing same, and methods of use therefor.

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18-04-2013 дата публикации

AMINO ACID GROUP-MODIFIED ORGANOPOLYSILOXANE AND SILANE, AMINO ACID GROUP-CONTAINING COMPOUND, AND PRODUCTION METHOD THEREOF

Номер: US20130096340A1
Автор: MORIYA Hiroyuki
Принадлежит: SHIN-ETSU CHEMICAL CO., LTD.

An amino acid-modified organopolysiloxane is provided. It has an amino acid derivative bonded to at least one silicon atom of the organopolysiloxane segment constituting the backbone of the organopolysiloxane via an amide bond represented by the following general formula (1): 3. A method according to wherein the compound represented by the general formula (13) is an aliphatic amine containing 6 to 32 carbon atoms.4. A method according to wherein the compound represented by the general formula (13) is a higher aliphatic amine containing 12 to 32 carbon atoms.5. A method according to wherein the compound represented by the general formula (13) is a hydroxy aliphatic amine containing 6 to 32 carbon atoms.6. A method according to wherein the compound represented by the general formula (14) is pyroglutamine acid. The present application is a 37 C.F.R. §1.53(b) divisional of, and claims priority to, U.S. application Ser. No. 13/584,166, filed Aug. 13, 2012. Application Ser. No. 13/584,166 is a divisional of, and claims priority to, U.S. application Ser. No. 12/965,203, filed Dec. 10, 2010. Priority is also claimed to Japanese Patent Application No. 2009-281099 filed Dec. 11, 2009, Japanese Patent Application No. 2009-281114 filed on Dec. 11, 2009 and Japanese Patent Application No. 2009-281126 filed on Dec. 11, 2009. The entire contents of each of these applications is hereby incorporated by reference.This invention relates to an amino acid-modified organopolysiloxane and silane, an amino acid group-containing compound, and production method thereof.Various compounds and methods have been investigated for use in producing an amino acid-modified or a peptide-modified silicone and for use in its production method.For example, in the case of a silicone modified with an amino acid derivative represented by the following formula:the silicone has a structure in which the amino group and the carboxy group of the amino acid have been protected. In addition, this silicone has been ...

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09-05-2013 дата публикации

NOVEL COMPOUNDS

Номер: US20130115179A1
Принадлежит:

The invention relates to novel polyglycerol based UV-filters as well as to topical compositions comprising such novel polyglycerol based UV-filters. Furthermore, the invention relates to the use of such novel polyglycerol based UV-filters to enhance the solubility of butyl methoxydibenzoylmethane or bis-ethylhexyloxyphenol methoxyphenyl triazine in cosmetic oils. 1. Polyglycerol based UV filters obtainable by a process comprising the steps ofa.) ring-opening polymerization of x mol equivalents of glycidol using 1 mol equivalent of a polyol starter unit with y mol equivalents hydroxyl-groups followed byb.) block copolymerization with z×(x+y) mole equivalents of propyleneoxide to form a hyperbranched polyether-polyol backbone carrying (x+y) mol equivalents hydroxyl-groups followed byc.) partial or total esterification of the hydroxyl groups with 2-(4-Diethylamino-2-hydroxybenzoyl)benzoic acidwherein x is an integer from 3-16, y is an integer from 1-6, and z is an integer from 0-10.2. The polyglycerol based UV filter according to claim 1 , wherein 15 to 100% claim 1 , more preferably 30-80% claim 1 , most preferably about 60-75% of the hydroxyl groups of the hyperbranched polyether-polyol backbone are esterified with 2-(4-Diethylamino-2-hydroxybenzoyl)benzoic acid.3. The polyglycerol based UV filter according to claim 1 , wherein the amount of glycidol units x is selected in the range of 3 to 16 mol equivalents per mol equivalent of the polyol starter unit.4. The polyglycerol based UV filter according to claim 1 , wherein the polyol starter unit is trimethylolpropane.5. The polyglycerol based UV filter according to claim 1 , wherein 60-75% of the terminal hydroxyl groups of the hyperbranched polyether-polyol backbone are linked to a 2-(4-Diethylamino-2-hydroxybenzoyl)benzoyl moiety and the residual terminal hydroxyl groups are linked to a capping group.6. The polyglycerol based UV filter according to claim 5 , wherein the capping group is a 2-ethyl hexanoyl claim 5 , ...

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09-05-2013 дата публикации

In-vivo gelling pharmaceutical pre-formulation

Номер: US20130116341A1
Принадлежит: Medicus Biosciences LLC

Provided herein are in vivo gelling pharmaceutical pre-formulations forming biocompatible hydrogel polymers that are polymerized in vivo and kits comprising at least one nucleophilic compound or monomer unit, at least one electrophilic compound or monomer unit, and optionally at least one therapeutic agent. The biocompatible hydrogel polymer is bioabsorbable and releases the therapeutic agent at a target site, avoiding systemic exposure.

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09-05-2013 дата публикации

Process for preparing saturated amino acids or saturated amino esters comprising a metathesis step

Номер: US20130116458A1

The subject matter of the invention is a process for synthesizing a saturated long-chain o.,0)-amino ester (acid) obtained in a first step by cross-metathesis between an acrylic first compound and a monounsaturated second compound comprising at least one nitrile, acid or ester trivalent function, one of these compounds comprising a nitrile function and the other an acid or ester function, in the presence of a ruthenium carbene metathesis catalyst, and in a second step by hydrogenation of the monounsaturated nitrile ester (acid) obtained in the presence of the metathesis catalyst of the preceding stop, acting as a hydrogenation catalyst.

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16-05-2013 дата публикации

DIAMINE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE A4 HYDROLASE

Номер: US20130123243A1
Принадлежит:

This invention is directed to compounds of formula (I): 3. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, cyano, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each independently hydrogen or halo.'}4. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, optionally substituted phenyl, furanyl, thienyl, thiazolyl, or optionally substituted oxazolyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each hydrogen.'}6. A compound according to wherein R an optionally substituted heteroaryl.7. A compound according to wherein R is furanyl claim 6 , oxazoyl claim 6 , pyrazolyl claim 6 , pyridinyl claim 6 , triazolyl claim 6 , thiazolyl claim 6 , or benzothiazolyl claim 6 , each of which is optionally substituted.8. A compound according to wherein:{'sup': 2', '7', '5a', '5b', '5c, 'Rand R, together with the nitrogens to which they are attached and one of R, Rand R, form an optionally substituted 6- to 10-membered bridged N-heterocyclyl.'}10. A compound according to wherein:{'sup': 3', '12', '12', '12, 'Ris a direct bond, —O—, —R—O—, —O—R—, —O—R—O—, or an optionally substituted straight or branched alkylene chain;'}{'sup': 4', '12a, 'Ris a direct bond, —O—R— or an optionally substituted straight or branched alkylene chain;'}{'sup': 8', '13', '10', '13', '10', '13', '10', '11, 'Ris aralkyl optionally substituted with one or more substituents selected from the group consisting of —R—OR, —R—C(═O)ORand —R—C(═O)N(R)R;'}{'sup': 9', '10, 'each Ris independently alkyl, halo or —O—R;'}{'sup': '12', 'Ris an optionally substituted straight ...

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16-05-2013 дата публикации

NOVEL CATIONIC LIPIDS AND METHODS OF USE THEREOF

Номер: US20130123338A1
Принадлежит: Protiva Biotherapeutics, Inc.

The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art. 2. The cationic lipid of claim 1 , wherein Rand Rare independently selected from the group consisting of a methyl group and an ethyl group.3. The cationic lipid of claim 1 , wherein Rand Rare both methyl groups.4. The cationic lipid of claim 1 , wherein Rand Rare joined to form an optionally substituted heterocyclic ring having from 2 to 5 carbon atoms and from 1 to 3 heteroatoms selected from the group consisting of nitrogen (N) claim 1 , oxygen (O) claim 1 , sulfur (S) claim 1 , and combinations thereof.5. The cationic lipid of claim 1 , wherein X is O claim 1 , C(O)O claim 1 , C(O)N(R) claim 1 , N(R)C(O)O claim 1 , or C(O)S.6. The cationic lipid of claim 1 , wherein Ris selected from the group consisting of hydrogen (H) and an optionally substituted methyl group claim 1 , ethyl group claim 1 , or C-Calkyl claim 1 , alkenyl claim 1 , or alkynyl group.7. The cationic lipid of claim 1 , wherein X is an optionally substituted heterocyclic ring having from 2 to 5 carbon atoms and from 1 to 3 heteroatoms selected from the group consisting of nitrogen (N) claim 1 , oxygen (O) claim 1 , sulfur (S) claim 1 , and combinations thereof.8. The cationic lipid of claim 1 , wherein Y is (CH)and n is 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 claim 1 , or 6.9. The cationic lipid of claim 8 , wherein n is 2 claim 8 , ...

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16-05-2013 дата публикации

Imaging Agents

Номер: US20130123618A1
Автор: Mark M. Goodman
Принадлежит: EMORY UNIVERSITY

This invention provides amino acid derivatives useful in detecting and evaluating brain and body tumors, including (1S,2S) anti-2-[ 18 F]FACPC and (1R,2R) anti-2-[ 18 F]FACPC.

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23-05-2013 дата публикации

METHODS AND COMPOSITIONS FOR DELIVERY OF ACTIVE AGENTS

Номер: US20130129785A1
Принадлежит: ALNYLAM PHARMACEUTICALS, INC

A lipid particle can include a cationic lipid. Synthesis of the cationic lipid can include a ylide-based reaction, such as a Wittig reaction or sulfur ylide reaction. In some cases, the synthesis can also include a Michael addition or a related addition reaction. 2. The compound of claim 1 , wherein X are Y are alkyl.3. The compound of claim 3 , wherein X and Y are both methyl.4. The compound of claim 1 , wherein Lis a linear alkylene unit.5. The compound of claim 1 , wherein Lis a linear alkylene unit.6. The compound of claim 5 , wherein Lcontains one or more double bonds and one or more cycloalkylene groups.7. The compound of claim 1 , wherein Rand Rare each claim 1 , independently claim 1 , C-Calkyl or C-Calkenyl.8. The compound of claim 7 , wherein one of Rand Ris a linear C-Calkyl or C-Calkenyl group and the other of Rand Ris a branched C-Calkyl or C-Calkenyl group.9. The compound of claim 1 , wherein Z is —C(O)O— claim 1 , —C(O)N(R)— claim 1 , —O(CO)N(R) claim 1 , —C(O)N(R)C(O)O— claim 1 , or —N(R)C(O)N(R)—.10. The compound of claim 1 , wherein Ris H or alkyl.11. The compound of claim 1 , wherein{'sub': 1', '4, 'X and Y are each, independently, C-Calkyl;'}{'sup': 1', '2, 'sub': 2', '10, 'Land Lare each, independently, an C-Clinear or branched alkylene linking unit, which may optionally contain one or more double bonds and further may optionally be interrupted by one or more heteroatoms and/or one or more cycloalkylene groups;'}{'sub': 1', '2', '10', '30, 'Rand Rare each, independently, a C-Caliphatic group, which may optionally contain one or more double bonds, and may optionally be interrupted by one or more heteroatoms and/or one or more cycloalkylene groups;'}{'sup': 3', '3', '3', '3', '3', '3', '3', '3, 'Z is —C(O)O—, —OC(O)—, —C(O)N(R)—, —N(R)C(O)—, —O(CO)N(R), —N(R)C(O)O—, —C(O)N(R)C(O)O—, —OC(O)N(R)C(O)— or —N(R)C(O)N(R)—;'}{'sup': '3', 'sub': 1', '4, 'each occurrence of Ris independently H or C-Calkyl; and'}{'img': [{'@id': 'CUSTOM-CHARACTER-00003', '@ ...

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23-05-2013 дата публикации

Esters with Antimicrobial, Bioresistant and Fungal Resistant Properties

Номер: US20130131365A1
Автор: Daly Thomas
Принадлежит:

A bromine/nitro moiety linked into the backbone of an ester or other compound over a wide range of occurrence rates provides antimicrobial, bio-resistant and fungal resistant properties for metal working fluids (MWF)s and other coatings. The moiety can be have the bromo and nitro groups linked to the same or different carbon atoms. The present invention also relates to urethanes, urea, amides, imides, carbonates, ethers, siloxanes, and many other types of linkages essential to MWF bases. 2. The anionic surfactant of where n=n′=7 claim 1 , m=m′=7 claim 1 , and A=Br.3. A metal working fluid base comprising a molecule according to .4. A foaming or anti-foaming agent comprising a molecule according to .6. The molecule of where R═R′=—(CH)CHA=—(CH2)CH.7. A metal working fluid base comprising a molecule according to .8. A surfactant comprising a molecule according to .9. A foaming or anti-foaming agent comprising a molecule according to . This is a continuation of application Ser. No. 13/351,512 filed Jan. 17, 2012 which was a continuation of Ser. No. 12/965,252 filed Dec. 10, 2010 which was a divisional from application Ser. No. 12/287,726 filed Oct. 10, 2008, now abandoned, which was a continuation-in-part of application Ser. No. 11/800,569 filed May 7, 2007, now U.S. Pat. No. 7,439,376 issued Oct. 21, 2008, which was a continuation in part of application Ser. No. 10/603,356 filed Jun. 25, 2003, now abandoned, which claimed priority from U.S. Provisional patent application No. 60/392,007 filed Jun. 26, 2002. Applications Ser. Nos. 13/351,512, 12/965,252, 12/287,726, 11/800,569, 10/603,356 and 60/392,007 are hereby incorporated by reference. This application also incorporates by reference my other patent application Ser. No. 10/350,928 filed Jan. 23, 2003 entitled Polymers with Antimicrobial, Bioresistant and Fungal Resistant Properties.The text of this continuation application is substantially identical to that of grandparent application Ser. No. 10/603,356.1. Field of ...

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30-05-2013 дата публикации

TRYPTOPHAN HYDROXYLASE INHIBITORS FOR THE TREATMENT OF METASTATIC BONE DISEASE

Номер: US20130137635A1
Автор: Sands Arthur Thomas
Принадлежит: LEXICON PHARMACEUTICALS, INC.

This invention relates to tryptophan hydroxylase inhibitors, compositions comprising them, and methods of their use for the treatment, management and/or prevention of metastatic bone disease. 2. The use of claim 1 , wherein the metastatic bone disease is osteosclerotic (osteoblastic).3. The use of claim 2 , wherein the metastatic bone disease is bone metastases of prostate cancer.4. The use of claim 3 , wherein the compound is used in combination with a therapeutically or prophylactically effective amount of a second drug.5. The use of claim 4 , wherein the second drug is a luteinizing hormone-releasing hormone agonist (e.g. claim 4 , leuprolide claim 4 , goserelin claim 4 , buserelin); an antiandrogen (e.g. claim 4 , flutamide claim 4 , nilutamide); or an adrenal gland inhibitor (e.g. claim 4 , ketoconazole claim 4 , aminoglutethimide).6. The use of claim 5 , wherein the second drug is mitoxantrone claim 5 , estramustine claim 5 , doxorubicin claim 5 , etoposide claim 5 , vinblastine claim 5 , paclitaxel claim 5 , carboplatin claim 5 , or vinorelbine.11. The pharmaceutical composition of claim 10 , wherein the second drug is mitoxantrone claim 10 , estramustine claim 10 , doxorubicin claim 10 , etoposide claim 10 , vinblastine claim 10 , paclitaxel claim 10 , carboplatin claim 10 , or vinorelbine. This invention relates to tryptophan hydroxylase inhibitors, compositions comprising them, and methods of their use for the treatment, management and/or prevention of metastatic bone disease.The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] is involved in multiple central nervous facets of mood control and in regulating sleep, anxiety, alcoholism, drug abuse, food intake, and sexual behavior. In peripheral tissues, serotonin is implicated in the regulation of vascular tone, gut motility, primary hemostasis, and cell-mediated immune responses. Walther, D. J., et al., 299:76 (2003). Some evidence also suggests that serotonin can affect bone growth. See, e.g., ...

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13-06-2013 дата публикации

Salts of Isophosphoramide Mustard and Analogs Thereof As Anti-Tumor Agents

Номер: US20130149296A1
Автор: Lee R. Morgan
Принадлежит: Dekk Tek Inc

The present disclosure relates to salts and compositions of isophosphoramide mustard and isophosphoramide mustard analogs. In one embodiment the salts can be represented by the formula I: (I) wherein A + represents an ammonium species selected from the protonated (conjugate acid) or quaternary forms of aliphatic amines and aromatic amines, including basic amino acids, heterocyclic amines, substituted and unsubstituted pyridines, guanidines and amidines; and X and Y independently represent leaving groups. Also disclosed herein are methods for making such compounds and formulating pharmaceutical compositions thereof. Methods for administering the disclosed compounds to subjects, particularly to treat hyperproliferative disorders, also are disclosed.

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13-06-2013 дата публикации

ALKYNE AND ALKENE DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE-1 RECEPTOR MODULATORS

Номер: US20130150331A1
Принадлежит: ALLERGAN, INC.

The present invention relates to novel alkyne and alkene derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors. 2. A compound according to claim 1 , wherein:{'img': {'@id': 'CUSTOM-CHARACTER-00015', '@he': '3.89mm', '@wi': '6.69mm', '@file': 'US20130150331A1-20130613-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'sup': 14', '15, '“” represents a double bond “—CR═CR—”.'}3. A compound according to claim 1 , wherein:{'sup': '1', 'sub': '2', 'Lis CH.'}4. A compound according to claim 1 , wherein:{'sup': '1', 'Lis O, S or NH.'}7. A compound according to claim 1 , selected from:[3-({4-[(1E)-4-(3,4-dimethylphenyl)-3-(3-fluorophenyl)but-1-en-1-yl]benzyl}amino)propyl]phosphonic acid; and3-({4-[(1E)-4-(3,4-dimethylphenyl)-3-(3-fluorophenyl)but-1-en-1-yl]benzyl}amino)propanoic acid.8. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound according to claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , diluents or carrier.9. A pharmaceutical composition according to claim 8 , wherein the compound is selected from:[3-({4-[(1E)-4-(3,4-dimethylphenyl)-3-(3-fluorophenyl)but-1-en-1-yl]benzyl}amino)propyl]phosphonic acid; and3-({4-[(1E)-4-(3,4-dimethylphenyl)-3-(3-fluorophenyl)but-1-en-1-yl]benzyl}amino)propanoic acid. This application is a Divisional of U.S. patent application Ser. No. 13/305,398, filed Nov. 28, 2011, which claims the benefit of U.S. Provisional Application Ser. No. 61/419,278 filed Dec. 3, 2010, both of which are hereby incorporated by reference in their entirety.The present invention relates to novel alkyne and alkene derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals, as modulators of sphingosine-1-phosphate receptors. The invention relates specifically to the use of ...

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13-06-2013 дата публикации

Pharmaceutical composition comprising a curcumin derivative

Номер: US20130150628A1
Автор: Thomas M. DiMauro
Принадлежит: Individual

The present invention is directed to a pharmaceutical composition comprising:

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20-06-2013 дата публикации

AMINO ACID-, PEPTIDE-AND POLYPEPTIDE-LIPIDS, ISOMERS, COMPOSITIONS, AND USES THEREOF

Номер: US20130158021A1
Принадлежит: Massachusetts Institute of Technology

Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: 2. (canceled)3. The compound of claim 1 , wherein each instance of Q is O.4. The compound of claim 1 , wherein at least one instance of Ris H.5. The compound of claim 1 , wherein Ris a group of formula (iv).6. The compound of claim 1 , wherein L is an optionally substituted alkylene.811-. (canceled)1534-. (canceled)3750-. (canceled)5359-. (canceled)61. (canceled)62. The composition of claim 60 , wherein the composition is a pharmaceutical composition claim 60 , a cosmetic composition claim 60 , a nutraceutical composition claim 60 , or a composition with non-medical application.6377-. (canceled)79. The method of claim 78 , wherein the desired property is solubility in water claim 78 , solubility at different pH claim 78 , ability to bind polynucleotides claim 78 , ability to bind heparin claim 78 , ability to bind small molecules claim 78 , ability to bind protein claim 78 , ability to form microparticles claim 78 , ability to increase transfection efficiency claim 78 , ability to support cell growth claim 78 , ability to support cell attachment claim 78 , ability to support tissue growth claim 78 , and/or intracellular delivery of the APPL and/or an agent complexed or attached thereto to aid in bioprocessing.81. The method of claim 80 , wherein the disease claim 80 , disorder claim 80 , or condition is selected from the group consisting of ...

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20-06-2013 дата публикации

Process for Preparing Crystalline 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic Acid and Use for Production of Primovist®

Номер: US20130158241A1
Принадлежит: Bayer Intellectual Property GmbH

The invention relates to a method for producing crystalline 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic acid of the formula I by saponifying 3,6,9-triaza-3,6,9-tris(tert-butoxycarbonylmethyl)-4-(4-ethoxybenzyl)-undecanedioic acid di-tert-butyl ester of the formula II in an aqueous alkali metal hydroxide solution and using 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic acid of the formula I for producing the gadolinium complex of 3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(4-ethoxybenzyl)undecanedioic acid [(Gd-EOB-DTPA)=Primovist®].

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20-06-2013 дата публикации

CANCER HEAT THERAPY-ENHANCING AGENT

Номер: US20130158293A1
Принадлежит:

Provided is an enhancer for cancer thermotherapy not combined with photodynamic therapy. Cancer treatment not combined with photodynamic therapy is made available by using, as an enhancer for cancer thermotherapy, 5-aminolevulinic acids represented by formula (1): 2. The enhancer for cancer thermotherapy according to claim 1 , wherein the 5-aminolevulinic acids or a salt thereof are not encapsulated inside a lipid membrane or in an internal aqueous phase thereof. The present invention relates to an enhancer for cancer thermotherapy, and more particularly to an enhancer for cancer thermotherapy not combined with photodynamic therapy (PDT), comprising 5-aminolevulinic acids or a salt thereof.Cancer (malignant tumor) is the most frequent cause of death in Japan, and one out of two Japanese is said to suffer from the disease. In addition, cancer is one of the leading causes of death among other developed countries. Accordingly, development of an effective treatment method for cancer has been a long-lasting goal of most people in the world including Japan. Cancer, however, derives from cells of a patient himself/herself. Thus, an effective therapeutic agent and/or method capable of effectively treating cancer without an adverse effect have not been easily developed, so that a potent therapeutic agent or method has yet to be reported.Examples of current major cancer treatment include surgical treatment, chemotherapy, and radiotherapy. Recently, the treatment has extended to include thermotherapy and photodynamic therapy.The above thermotherapy is a treatment method which takes advantage of the fact that cancer cells are heat-sensitive in nature compared to normal cells, and specifically inhibits proliferation of the cancer cells. That is, when a tissue containing cancer and normal cells is heated at about 42 to 43° C.., homeostasis plays a role in the section of the normal cells to expand blood vessels surrounding the cells, thereby increasing their blood flow and ...

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27-06-2013 дата публикации

TETRASUBSTITUTED BENZENES

Номер: US20130165486A1
Принадлежит: EnVivo Pharmaceuticals, Inc.

Tetrasubstituted benzenes that act as modulators of gamma secretase and their use in the treatment of one or more symptoms of treating neurodegenerative disorders, e.g., Alzheimer's disease, are described. 162.-. (canceled)64. The compound of claim 63 , wherein Rand Rare independently selected from the group consisting of (a) H claim 63 , (b) (C-C)alkyl and (c) (C-C)alkyl-(C-C)cycloalkyl provided that both Rand Rare not H claim 63 , wherein each alkyl or cycloalkyl of Rand Ris optionally independently substituted with one or more groups selected from the group consisting of halo claim 63 , hydroxy claim 63 , cyano claim 63 , CFand (C-C)alkyl claim 63 ,or{'sub': 1', '2', '1', '4', '3', '1', '4, 'Rand Rtaken together with the carbon to which they are attached form a 3-7 membered cycloalkyl or heterocycloalkyl ring which optionally bears a C-Calkyl substituent that can be optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, oxo, cyano, CFand (C-C)alkyl,'}or{'sub': 1', '2', '20', '21', '20', '21', '3', '1', '4, 'Rand Rare taken together with the carbon to which they are attached form a 3-7 membered cycloalkyl ring substituted with Rand Rwherein Rand Rtaken together with the carbon or carbons to which they are attached form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, cyano, CFand (C-C)alkyl;'}Y is —O—,{'sub': '4', 'claim-text': [{'sub': 0', '3', '3', '7, '(a) (C-C)alkyl(C-C)cycloalkyl,'}, '(b) trifluoroethyl and', '(c) trifluoropropyl;', {'sub': 6', '3', '2', '1', '4', '2', '2', '3', '6', '6', '2', '6, 'Z is a phenyl ring optionally bearing up to 3 substituents independently selected from the group consisting of halogen, R, CF, CN, NO, OH, (C-C)alkoxy, OCHCHOCH, SR, S(O)Rand S(O)R;'}], 'Ris selected from the group consisting of'}{'sub': 5', '3, 'claim-text': [{'sub': '6', 'Ris selected ...

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27-06-2013 дата публикации

HOMO- AND HETERO-POLYAMINO-ACID DERIVATIVES OF FULLERENE C60, METHOD FOR PRODUCING SAME, AND PHARMACEUTICAL COMPOSITIONS BASED ON SAID DERIVATIVES

Номер: US20130165691A1
Принадлежит:

The invention relates to the pharmaceutical industry and to medicine, specifically to novel homo- and hetero-polyamino-acid derivatives of fullerene Cof general formula: C(H){NH(CH)COO—}{NH(L)COOH)}, where n=2-5, x=3, L=—(CH), where m=1-5, or —CO(CH)CH(NH)—, where k=1-2, characterized in that the compounds comprise covalently bonded amino-acid groups and polar ionic forms of the amino acids, and also to a method for producing said derivatives, and to the production of pharmaceutical compositions based on same. The method for producing homo- and hetero-polyamino-acid derivatives of fullerene is based on the reaction of a nucleophilic bond of amino acids to fullerene, forming covalently bonded amino-acid derivatives of fullerene, with the subsequent introduction of polar ionic forms of the amino acids. A pharmaceutical composition comprises, as active substance, homo- and hetero-polyamino-acid derivatives of fullerene of formula 1. Homo- and heteropoly(amino acid) derivatives of fullerene of general formula C(H){NH(CH)COO—}{NH(L)COOH)} , wherein n=2-5 , x=3 , L=—(CH) , wherein m=1-5 , or —CO(CH)CH(NH)— , wherein k=1-2 , characterized in that the compounds comprise covalently bonded amino acid groups and polar ionic forms of amino acids.2. Fullerene derivatives according to claim 1 , characterized in that the amino acid groups are moieties of aliphatic amino acids of general formula NH(CH)COOH claim 1 , wherein n=2-5.3. Fullerene derivatives according to claim 1 , characterized in that the polar ionic forms of amino acids are moieties of dicaboxylic amino acid amides of general formula NH(CO)(CH)CH(NH)COOH claim 1 , wherein k=1-2.4. A method for producing the fullerene derivatives according to claim 1 , characterized in that the fullerene derivatives are produced by reacting fullerene with a tenfold molar excess of anhydrous potassium salts of amino acids of general formula NH(CH)COOK claim 1 , wherein n=2-5 claim 1 , in an aromatic organic solvent medium claim 1 , ...

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27-06-2013 дата публикации

HYDRATED N-FULLERENE AMINO ACIDS, METHOD FOR PRODUCING THE LATTER, AND PHARMACEUTICAL COMPOSITIONS ON THE BASIS THEREOF

Номер: US20130165692A1
Принадлежит:

The invention relates to the pharmaceutical industry and to medicine, specifically to novel hydrated amino-acid derivatives of fullerene Cof general formula C(H){NH(CH)COOH}.xHO, where C-fullerene, n=5, 6, 7, x=8-10, and also to a method for producing said derivatives, and to the production of pharmaceutical compositions on the basis thereof. Hydrated N-fullerene amino acids are formed in the interaction of fullerene with 15 times the molar excess of anhydrous potassium salts of amino acids in a medium of organic aromatic solvent with slow addition to the resultant suspension of an interphase catalyst and with mixing and heating to a temperature not exceeding 60° C. until the solution is completely decolorized and a solid residue formed, after which the latter is separated out, and then 0.8 M of aqueous solutions of potassium salts of fullerene amino-acid derivatives is treated with a solution of organic or mineral acids, followed by centrifugation, rinsing and drying of the residue. A pharmaceutical composition which exhibits activity against the herpes virus, flu viruses of various origin and HIV, and also anti-tumor and anti-psoriatic activity, comprising, as active substance, an effective quantity of hydrated N-fullerene amino acids. 1. Hydrated N-fullerene amino acids of general formula C(H){NH(CH)COOH}xHO , wherein Cis fullerene; n=5 , 6 , or 7; and x=8 to 10.2. A method for producing the compound according to claim 1 , characterized in that the fullerene is reacted with a 15-fold molar excess of anhydrous potassium salts of amino acids of general formula NH(CH)COOH claim 1 , wherein n=5 claim 1 , 6 claim 1 , or 7 claim 1 , in an aromatic solvent medium claim 1 , comprising a slow addition to the resulting suspension of a phase-transfer catalyst under stirring and heating to a temperature not higher than 60 to 80° C. until the solution is completely decolorized and a solid residue is formed claim 1 , wherein said residue represents potassium salts of the ...

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27-06-2013 дата публикации

PROCESS FOR PREPARING 4-AMINO-5-HEXENOIC ACID AND INTERMEDIATES THEREOF

Номер: US20130165693A1
Принадлежит: TARGEON

The present invention relates to a new and competitive process for the preparation of 4-amino-5-hexenoic acid and intermediates thereof. The compound, and compositions containing the compound as an active ingredient, can be used for the treatment and/or prophylaxis of epilepsy and West syndrome. 1. A process for producing 4-amino-5-hexenoic acid using succinimide as raw material , characterized in that it comprises at least a first step a) consisting of reducing said succinimide with a hydride donor in an alcoholic solvent in presence of a protic acid to produce a 5-alkoxy-2-pyrrolidone intermediate.2. A process according to which further comprises the following steps:b) reacting said 5-alkoxy-2-pyrrolidone intermediate with at least 2 equivalents of a vinyl magnesium halide reagent (vinyl Grignard reagent) in a suitable solvent, to form 5-vinyl-2-pyrrolidone; andc) hydrolyzing said 5-vinyl-2-pyrrolidone to form 4-amino-5-hexenoic acid.3. A process according to claim 2 , where the vinyl magnesium halide reagent of step b) is present in the amount of 2 to 3 molar equivalents.4. A process according to claim 2 , where the vinyl magnesium halide reagent of step b) is present in the amount of 2 to 2.5 molar equivalents.5. A process according to claim 2 , wherein steps a) and b) are being undertaken without isolation of the 5-alkoxy-2-pyrrolidone intermediate.6. A process according to claim 2 , wherein steps a) claim 2 , b) and c) are being undertaken without isolation of the 5-alkoxy-2-pyrrolidone or 5-vinyl-2-pyrrolidone intermediates.7. A process according to claim 1 , which further comprises the following steps:b) submitting said 5-alkoxy-2-pyrrolidone intermediate to i) one equivalent of a basic reagent in a suitable solvent, and ii) at least one equivalent of a vinyl magnesium halide reagent (vinyl Grignard reagent), to form 5-vinyl-2-pyrrolidone, the two steps being undertaken in the same reaction vessel, andc) hydrolyzing said 5-vinyl-2-pyrrolidone to 4-amino-5- ...

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04-07-2013 дата публикации

3-[4-(PHENYLAMINOOXALYLAMINO)PHENYL]HEX-4-YNOIC ACIDS, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS A MEDICAMENT

Номер: US20130172248A1
Принадлежит:

The invention relates to 3-[4-(phenylaminooxalylamino)phenyl]hex-4-ynoic acids, and to physiologically compatible salts thereof. 2. A compound as claimed in claim 1 , wherein{'sub': '3', 'R1 is H, F, CH;'}{'sub': '3', 'R2 is F, CH;'}{'sub': '3', 'R3 is F, CH;'}{'sub': 3', '3, 'R4 is H, Cl, CH, CF;'}and physiologically compatible salts thereof.9. (canceled)10. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.11. The pharmaceutical composition as claimed in claim 10 , which comprises at least one further active ingredient.12. The pharmaceutical composition as claimed in claim 11 , which comprises claim 11 , as a further active ingredient claim 11 , one or more antidiabetics claim 11 , active hypoglycemic ingredients claim 11 , HMG-CoA reductase inhibitors claim 11 , cholesterol absorption inhibitors claim 11 , PPAR gamma agonists claim 11 , PPAR alpha agonists claim 11 , PPAR alpha/gamma agonists claim 11 , PPAR delta agonists claim 11 , fibrates claim 11 , MTP inhibitors claim 11 , bile acid absorption inhibitors claim 11 , CETP inhibitors claim 11 , polymeric bile acid adsorbers claim 11 , LDL receptor inducers claim 11 , ACAT inhibitors claim 11 , antioxidants claim 11 , lipoprotein lipase inhibitors claim 11 , ATP citrate lyase inhibitors claim 11 , squalene synthetase inhibitors claim 11 , lipoprotein(a) antagonists claim 11 , HM74A receptor agonists claim 11 , lipase inhibitors claim 11 , insulins claim 11 , sulfonylureas claim 11 , biguanides claim 11 , meglitinides claim 11 , thiazolidinediones claim 11 , alpha-glucosidase inhibitors claim 11 , active ingredients which act on the ATP-dependent potassium channel of the beta cells claim 11 , glycogen phosphorylase inhibitors claim 11 , glucagon receptor antagonists claim 11 , activators of glucokinase claim 11 , inhibitors of gluconeogenesis claim 11 , inhibitors of fructose 1 claim 11 ,6-biphosphatase claim 11 , modulators of glucose transporter 4 claim ...

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11-07-2013 дата публикации

Quinazoline derivatives

Номер: US20130178624A1
Принадлежит: Janssen Pharmaceutica NV

The present invention concerns the compounds of formula wherein Z represents NH; Y represents —C 3-9 alkyl-, —C 2-9 alkenyl-, —C 3-7 alkyl-CO—NH optionally substituted with amino, mono- or di(C 1-4 alkyl)amino or C 1-4 alkyloxycarbonylamino-, —C 3-7 alkenyl-CO—NH— optionally substituted with amino, mono- or di(C 1-4 alkyl)amino- or C 1-4 alkyloxycarbonylamino-, C 1-5 alkyl-NR 13 —C 1-5 alkyl-, —C 1-5 alkyl-NR 14 —CO—C 1-5 alkyl-, —C 1-6 alkyl-CO—NH—, —C 1-5 alkyl-CO NR 15 —C 1-5 alkyl-, —C 1-3 alkyl-NH—CO-Het 20 -, —C 1-2 alkyl-CO-Het 21 -CO—, —C 1-2 alkyl-NH—CO—CR 16 R 17 —NH—, —C 1-2 alkyl-CO—NH—CR 18 R 19 —CO—, —C 1-2 alkyl-CO—NR 20 —C 1-3 alkyl-CO—, or —NR 22 —CO—C 1-3 alkyl-NH—; X 1 represents a direct bond, O or —O—C 1-2 alkyl-; X 2 represents a direct bond, —CO—C 1-2 alkyl-, NR 12 , —NR 12 —C 1-2 alkyl, —O—N═CH— or —C 1-2 alkyl-; R 1 and R 2 are hydrogen or halo; R 3 are hydrogen; R 4 represents hydrogen or C 1-4 alkyloxy; R 12 and R 13 are hydrogen or C 1-4 alkyl; R 14 and R 15 are hydrogen; R 16 and R 17 each independently represent hydrogen or C 1-4 alkyl; R 18 and R 19 are hydrogen or C 1-4 alkyl optionally substituted with phenyl or hydroxy; R 20 and R 21 are hydrogen or C 1-4 alkyl optionally substituted with C 1-4 alkyloxy; Het 20 , Het 21 and Het 22 are a heterocycle selected from the group consisting pyrrolidinyl, 2-pyrrolidinonyl or piperidinyl optionally substituted with hydroxy.

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11-07-2013 дата публикации

PROCESS FOR THE SYNTHESIS OF TAPENTADOL AND INTERMEDIATES THEREOF

Номер: US20130178644A1
Принадлежит: EUTICALS S.P.A.

The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high stereoselectivity due to the presence of the benzyl group as substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol equilibrium towards the desired enantiomer and amplifies the capacity of the stereocenter present in the compound (VII) to orient the nucleophilic addition of the organometallic compound at the carbonyl towards the desired stereoisomer. This substitution thus allows obtaining a considerable increase of the yields in this step, and consequently allows significantly increasing the overall yield of the entire tapentadol synthesis process. 130-. (canceled)32. The process according to claim 31 , wherein the halide is bromide and the metal is zinc or magnesium.33. The process according to claim 31 , wherein the ethyl metal halide is ethylmagnesium bromide.34. The process according to claim 32 , wherein the ethyl metal halide is used in a quantity between 1 and 5 equivalents with respect to compound (VIII).35. The process according to claim 31 , wherein the alkylation is carried out at a temperature between 0° C. and the boiling temperature of the solvent.36. The process according to claim 35 , wherein the alkylation is carried out at a temperature between 10 and 30° C.38. The process according to claim 37 , wherein the chiral acid is selected from D(−) mandelic acid claim 37 , D(−) 2-chloromandelic acid claim 37 , D(−) tartaric acid claim 37 , and (2R claim 37 ,3R)-O claim 37 ,O′-dibenzoyl tartaric acid.39. The process according to claim 38 , wherein the chiral acid is D(−) mandelic acid.40. The process according to claim 37 , wherein the polar solvent of step a′) is selected from: water claim 37 , aliphatic ketones and/or aliphatic alcohols claim 37 , used ...

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25-07-2013 дата публикации

ENZYMATIC CONJUGATION OF POLYPEPTIDES

Номер: US20130189287A1
Принадлежит:

The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions 1. An antibody or antibody fragment comprising a functionalized acceptor glutamine residue , the functionalized acceptor glutamine residue having Formula IVa ,{'br': None, 'sub': n', 'z', 'q', 'q', 'r, '(Q)-NH—(C)—X-L-(V—(Y—(Z))))\u2003\u2003Formula IVa'}or a pharmaceutically acceptable salt or solvate thereof,wherein:Q is glutamine residue present in an antibody or antibody fragment;{'sub': 'n', '(C)is a substituted or unsubstituted alkyl or heteroalkyl chain, optionally wherein any carbon of the chain is substituted with an alkoxy, hydroxyl, alkylcarbonyloxy, alkyl-S—, thiol, alkyl-C(O)S—, amine, alkylamine, amide, or alkylamide;'}n is an integer selected from among the range of 2 to 20;X is NH, O, S, absent, or a bond;L is independently absent, a bond or a continuation of a bond, or a carbon comprising framework of 5 to 200 atoms substituted at one or more atoms;r is an integer selected from among 1, 2, 3 or 4;q is an integer selected from among 1, 2, 3 or 4;z is an integer selected from among 1, 2, 3 or 4; andV is independently absent, a bond or a continuation of a bond, a non-cleavable moiety or a conditionally-cleavable moiety;Y is independently absent, a bond or a continuation of a bond, or a spacer system which is comprised of 1 or more spacers; andZ is a moiety that improves pharmacokinetic properties, a therapeutic moiety or a diagnostic moiety, wherein Z is an organic compound that is electrically negatively charged, hydrophobic and/or that has a molecular weight of at least 400 g/mol.2. The antibody of claim 1 , wherein n is an integer selected from among the range of 10 to 20.3. The antibody of claim 1 , wherein (C)is a heteroalkyl chain that comprises a (CH—CH—O—)group claim 1 , wherein x is ...

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25-07-2013 дата публикации

CRYSTALLINE FORMS OF 4-[2-(4-METHYLPHENYLSULFANYL)-PHENYL] PIPERIDINE WITH COMBINED SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITION FOR THE TREATMENT OF NEUROPATHIC PAIN

Номер: US20130190352A1
Принадлежит: H. Lundbeck A/S

Crystalline forms of 4-[2-(4-methylphenylsulfanyl)-phenyl]piperidine and salts thereof are provided e.g. for the treatment of neuropathic pain. 2. The compound according to claim 1 , which compound is the HBr addition salt.34-. (canceled)5. The compound according to claim 1 , which compound is the DL-lactic acid addition salt.67-. (canceled)8. The compound according to claim 1 , which compound is the glutaric acid addition salt (1:1).910-. (canceled)11. The compound according to claim 1 , which compound is the malonic acid addition salt (1:1).12. The compound according to claim 11 , which compound is characterized by peaks in an XRPD at 10.77° claim 11 , 16.70° claim 11 , 19.93° and 24.01°2θ claim 11 , or at 6.08° claim 11 , 10.11° claim 11 , 18.25° and 20.26°2θ.1310. The compound according to claim 11 , which compound is characterised by an XRPD as depicted in or .14. The compound according to which compound is L-aspartic acid addition salt (1:1) or L-aspartic acid addition salt hydrate (1:1).15. The compound according to which compound is glutamic acid addition salt (1:1) or glutamic acid addition salt monohydrate.16. (canceled)17. A pharmaceutical composition comprising a compound according to together with a pharmaceutically acceptable excipient.18. A method of treating a disease selected from chronic pain claim 1 , depression in partial responders claim 1 , treatment resistant depression claim 1 , Alzheimer's disease claim 1 , cognitive impairment claim 1 , ADHD claim 1 , melancholia claim 1 , PTSD claim 1 , hot flushes claim 1 , sleep apnea claim 1 , alcohol claim 1 , nicotine or carbohydrate craving claim 1 , substance abuse claim 1 , alcohol or drug abuse claim 1 , emesis claim 1 , eating disorders claim 1 , IBS claim 1 , affective disorders claim 1 , depression claim 1 , major depressive disorder claim 1 , postnatal depression claim 1 , depression associated with bipolar disorder claim 1 , Alzheimer's disease claim 1 , psychosis or Parkinson's disease claim ...

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01-08-2013 дата публикации

Mglu 2/3 agonists

Номер: US20130197079A1
Принадлежит: Eli Lilly and Co

The present invention provides novel mGlu2/3 agonists useful in the treatment of neurological or psychiatric disorders.

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01-08-2013 дата публикации

Short synthesis of tolterodine, intermediates and metabolites

Номер: US20130197082A1
Автор: Damjan Sterk
Принадлежит: Lek Pharmaceuticals dd

A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

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01-08-2013 дата публикации

ANTIPROLIFERATIVE COMPOUNDS, CONJUGATES THEREOF, METHODS THEREFOR, AND USES THEREOF

Номер: US20130197259A1
Принадлежит: Medarex, Inc.

Antiproliferative compounds having a structure represented by formula (II), where n, R, R, R, R, and Rare as defined herein, can be used to treat tumors, optionally when conjugated to a ligand such as an antibody: 2. A compound according to claim 1 , wherein Ris H or C-Calkyl.3. A compound according to claim 2 , wherein Ris Me.4. A compound according to claim 1 , wherein Ris H claim 1 , Boc (t-butoxycarbonyl) claim 1 , Troc (2 claim 1 ,2 claim 1 ,2-trichloroethoxy carbonyl) claim 1 , Bpoc ((1-methyl-1-(4-biphenyl)ethoxycarbonyl)) claim 1 , Cbz (benzyloxy carbonyl) claim 1 , Aloc (allyloxycarbonyl) claim 1 , methyl amine claim 1 , or Fmoc (9-fluorenylmethoxycarbonyl).5. A compound according to claim 4 , wherein Ris H or C-Calkyl.6. A compound according to claim 5 , wherein Ris Me. This application is a divisional of application Ser. No. 12/846,493, filed Jul. 29, 2010, now allowed; which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Applications Nos. 61/230,932, filed Aug. 3, 2009; and 61/232,883, filed Aug. 11, 2009; the disclosures of which are incorporated herein by reference.This invention relates to compounds structurally related to the tubulysins, conjugates thereof with a ligand, methods for making and using such compounds and conjugates, and compositions comprising such compounds and conjugates.The tubulysins are cytotoxins originally isolated from cultures of the myxobacteria or , with each organism producing a different mixture of tubulysins (Sasse et al. 2000; Reichenbach et al. 1998). Their crystal structure and biosynthetic pathway have been elucidated (Steinmetz et al. 2004) and their biosynthesis genes have been sequenced (Hoefle et al. 2006b). Pretubulysin, a biosynthetic precursor of the tubulysins, also has been shown to possess significant activity in its own right (Ullrich et al. 2009). (Full citations for the documents cited herein by first author or inventor and year are listed at the end of this specification.)The tubulysins ...

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08-08-2013 дата публикации

NAPHT-2-YLACETIC ACID DERIVATIVES TO TREAT AIDS

Номер: US20130203727A1
Принадлежит: Gilead Sciences, Inc.

The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula (I). 2. The compound of wherein Ris (C-C)alkyl claim 1 , (C-C)alkenyl or —O(C-C)alkyl wherein any (C-C)alkyl or (C-C)alkenyl of Ris optionally substituted with one or more groups selected from —O(C-C)alkyl claim 1 , halo claim 1 , oxo and —CN; and wherein Ris H.4. The compound of wherein Ris selected from:{'sub': 1', '6', '2', '6', '1', '6', '3', '7', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6, 'a) aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and heteroaryl is optionally substituted with one or more groups each independently selected from halo, (C-C)alkyl, (C-C)alkenyl, (C-C)haloalkyl, (C-C)cycloalkyl, —OH, —O(C-C)alkyl, —SH, —S(C-C)alkyl, —NH, —NH(C-C)alkyl and —N((C-C)alkyl), wherein (C-C)alkyl is optionally substituted with hydroxy, —O(C-C)alkyl, cyano or oxo;'}{'sub': 3', '14', '3', '14', '3', '7, 'sup': 1', '1, 'b) (C-C)carbocycle, wherein (C-C)carbocycle is optionally substituted with one or more Zgroups, wherein two Zgroups together with the atom or atoms to which they are attached optionally form a (C-C)carbocycle or heterocycle; and'}{'sup': 7', '1, 'c) aryl, heteroaryl and fused-heterocycle, wherein any aryl, heteroaryl and fused-heterocycle is substituted with one or more Zgroups and optionally substituted with one or more Zgroups.'}5. The compound of wherein Ris selected from:{'sub': 1', '6', '2', '6', '1', '6', '3', '7', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6, 'a) aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and ...

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08-08-2013 дата публикации

SUBSTITUTED 8-ALKOXY-2-AMINOTETRALIN DERIVATIVES, AND USE THEREOF

Номер: US20130203751A1
Принадлежит: Bayer Intellectual Property GmbH

The present application relates to novel substituted 8-alkoxy-2-aminotetraline derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular disorders. 5. (canceled)6. A method for the treatment and/or prevention of heart failure claim 1 , angina pectoris claim 1 , hypertension claim 1 , pulmonary hypertension claim 1 , ischemias claim 1 , vascular disorders claim 1 , thromboembolic disorders and arteriosclerosis comprising administering and effective amount of a compound of to a human or animal in need thereof.7. (canceled)8. A pharmaceutical composition comprising a compound of in combination with one or more inert claim 1 , non-toxic claim 1 , pharmaceutically suitable excipients.9. The pharmaceutical composition of claim 8 , further comprising an at least one active ingredients selected from the group consisting of an organic nitrate claim 8 , an NO donors claim 8 , a cGMP-PDE inhibitor claim 8 , a stimulator of guanylate cyclase claim 8 , an agent having antithrombotic activity claim 8 , an agent lowering blood pressure claim 8 , and an agent altering lipid metabolism.10. (canceled) The present application relates to novel substituted 8-alkoxy-2-aminotetraline derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular disorders.One of the most important cellular transmission systems in mammalian cells is cyclic guanosine monophosphate (cGMP). Together with nitric oxide (NO), which is released from the endothelium and transmits hormonal and mechanical signals, it forms the NO/cGMP system. Guanylate cyclases catalyze the biosynthesis of cGMP from ...

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08-08-2013 дата публикации

Ionic Viscoelastics and Viscoelastic Salts

Номер: US20130204010A1
Принадлежит: Boston University

One embodiment of the present invention relates to ionic liquids and ionic viscoelastics formed between [1] a small molecule or macromolecule containing two or more cations; and [2] a small molecule or macromolecule containing two or more anions. Another embodiment of the invention is the use of the inventive ionic liquids and ionic viscoelastics, formed between a small molecule or macromolecule containing two or more cations and a small molecule or macromolecule containing two or more anions, to form a crosslinked network. In certain embodiments, the ionic liquids formed can be viscous liquids, viscous liquid formed networks, or viscoelastic networks/gels. In certain embodiments, the ionic material of the invention may be used for a variety of applications including, but not limited to, lubricants, additives, gas separation, liquid separation, membranes, fuel cells, sensors, batteries, coatings, heat storage, liquid crystals, biocompatible fluids, solvents, and electronic materials.

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08-08-2013 дата публикации

ANTIPROLIFERATIVE COMPOUNDS, CONJUGATES THEREOF, METHODS THEREFOR, AND USES THEREOF

Номер: US20130204033A1
Принадлежит: Medarex, Inc.

Antiproliferative compounds having a structure represented by formula (II), where n, R, R, R, R, and Rare as defined herein, can be used to treat tumors, optionally when conjugated to a ligand such as an antibody: 2. A compound according to claim 1 , wherein Rand Rare independently selected from H claim 1 , Boc claim 1 , Troc claim 1 , Bpoc claim 1 , Cbz claim 1 , Aloc claim 1 , methylamine claim 1 , and Fmoc.3. A compound according to claim 2 , wherein Ris H or C-Calkyl.4. A compound according to claim 3 , wherein Ris Me.5. A compound according to claim 1 , wherein Ris H or C-Calkyl.6. A compound according to claim 5 , wherein Ris Me.7. A compound according to claim 1 , wherein Rand Rare different amine protecting groups.8. A compound according to claim 7 , wherein Ris H or C-Calkyl.9. A compound according to claim 8 , wherein Ris Me. This application is a divisional of application Ser. No. 12/846,493, filed Jul. 29, 2010, now allowed; which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Applications Nos. 61/230,932, filed Aug. 3, 2009; and 61/232,883, filed Aug. 11, 2009; the disclosures of which are incorporated herein by reference.This invention relates to compounds structurally related to the tubulysins, conjugates thereof with a ligand, methods for making and using such compounds and conjugates, and compositions comprising such compounds and conjugates.The tubulysins are cytotoxins originally isolated from cultures of the myxobacteria or , with each organism producing a different mixture of tubulysins (Sasse et al. 2000; Reichenbach et al. 1998). Their crystal structure and biosynthetic pathway have been elucidated (Steinmetz et al. 2004) and their biosynthesis genes have been sequenced (Hoefle et al. 2006b). Pretubulysin, a biosynthetic precursor of the tubulysins, also has been shown to possess significant activity in its own right (Ullrich et al. 2009). (Full citations for the documents cited herein by first author or inventor and year are ...

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15-08-2013 дата публикации

ANTI-INFECTIVE AND IMMUNOMODULATORY COMPOUNDS

Номер: US20130209515A1
Принадлежит:

The present invention provides pharmaceutical compositions and methods that include the use of anti-infective compounds that potentiate the host-immune response or limit or prevent the expression or activity of individual virulence factors. In addition, the compositions have immunomodulatory activity, and therefore can be used to prime host defenses to prevent or limit bacterial, fungal, and viral viability. In the compositions and methods of the inventions, specific steps of the bacterial-, fungal-, or viral-host interaction are targeted to prevent pathogenesis (e.g., infection). Such an approach should prevent pathogenic organisms from acquiring resistance to the protective anti-infective compounds. 114-. (canceled)16. The method of claim 15 , wherein said compound is 2′-aminoacetophenone.17. The method of claim 15 , wherein said compound is 2′-amino-3-hydroxyacetophenone.18. The method of claim 15 , wherein said disease is a bacterial infection claim 15 , a viral infection claim 15 , an autoimmune disease claim 15 , an allergic condition claim 15 , or cancer.19. The method of claim 18 , wherein said bacterial infection is the result of a Gram-negative bacterium.20Vibrio harveyi, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio alginolyticus, Pseudomonas phosphoreum, Pseudomonas aeruginosa Yersinia enterocolitica, Escherichia coli, Salmonella typhimurium, Haemophilus influenzae, Helicobacter pylori, Bacillus subtilis, Borrelia burgfdorferi, Neisseria meningitidis, Neisseria gonorrhoeae, Yersinia pestis, Campylobacter jejuni, Deinococcus radiodurans, Mycobacterium tuberculosis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenesStaphylococcus aureus.. The method of claim 18 , wherein said bacterial infection is the result of claim 18 , or22. The method of claim 21 , wherein said disease is the result of a bacterial infection claim 21 , fungal infection claim 21 , or viral infection.23. The method of claim 22 , wherein said bacterial infection is ...

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15-08-2013 дата публикации

NEW SALT OF A PYRIMIDIN DERIVATIVE

Номер: US20130210848A1
Принадлежит: LABORATORIOS SENOSIAIN S.A. DE C.V.

The present invention relates to a salt of a pyrimidin derivative of the acid (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamide)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic, to a method for preparing same and to the use thereof in formulating pharmaceutical formulations. 19-. (canceled)10. (3R ,5S ,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamide)-6-(propan-2-yl) pyrimidin-5-yl]-3 ,5-dihydroxihept-6-enoic amino acid salt , wherein the amino acid is lysine and wherein the bond formed between these two entities is a non-covalent bond.11. (3R ,5 S ,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamide)-6-(propan-2-yl)pyrimidin-5-yl]-3 ,5-dihydroxihept-6-enoic amino acid salt , wherein the amino acid is histidine and wherein the bond formed between these two entities in a non-covalent bond.12. A pharmaceutical composition comprising the salt of claim 10 , in combination with a pharmaceutically acceptable carrier.13. A pharmaceutical composition comprising the salt of claim 11 , in combination with a pharmaceutically acceptable carrier.14. A method of manufacturing a pharmaceutical composition comprising the step of adding the salt of to a pharmaceutically acceptable carrier.15. A method of manufacturing a pharmaceutical composition comprising the step of adding the salt of to a pharmaceutically acceptable carrier.16. The method according to claim 14 , wherein the pharmaceutical compositions are in the form of tablets or capsules.17. A method of manufacturing medicaments for the prevention or treatment of cardiovascular diseases comprising the step of adding the compound of to a pharmaceutically acceptable carrier.18. A process for synthesizing a rosuvastatin-lysine salt claim 10 , comprising the steps:a) subjecting the rosuvastatin calcium salt to a dissociation process; andb) mixing the acid rosuvastatin resulting from the previous step with an aqueous solution containing lysine for forming the salt in the presence of a methanol/ethyl ...

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15-08-2013 дата публикации

LIPASE INHIBITORS

Номер: US20130210883A1
Принадлежит:

The invention provides a compound of formula (I) as defined herein 3. A compound of wherein Ris thiophenyl claim 1 , piperidinyl claim 1 , indolyl or methylindolyl.4. A compound of wherein Ris selected from phenyl claim 1 , benzyl claim 1 , pyridyl claim 1 , furanyl claim 1 , thiophenyl claim 1 , pyrrolyl.5. A compound of wherein Ris selected from pyrrazolyl claim 1 , pyridinyl claim 1 , thienyl claim 1 , and furanyl.7. A compound of wherein Ris phenyl.8. A compound of having an ICfor lipase activity of less than 40 uM.9. A compound of wherein the lipase is ATGL.10. A compound of claim 1 , for use in the treatment or prevention of a disorder.11. A compound of claim 10 , for use in the treatment or prevention of diabetes type II claim 10 , stroke claim 10 , atherosclerosis claim 10 , coronary artery disease claim 10 , high triglyceride levels claim 10 , cachexia claim 10 , or its associated or related disorders or conditions claim 10 , including weight loss claim 10 , muscle atrophy or wasting claim 10 , fat loss claim 10 , reduced WAT.12. A method of inhibiting the activity of a lipase in vitro claim 1 , by contacting said lipase with a compound of formula (I) as per .13. A method of wherein the lipase is ATGL.14. A pharmaceutical composition comprising the compound of formula (I) as per and a pharmaceutically acceptable excipient.15. A method for treating or preventing diabetes type II claim 1 , coronary artery disease claim 1 , atherosclerosis claim 1 , stroke claim 1 , cachexia claim 1 , or its associated or related disorders or conditions claim 1 , including weight loss claim 1 , muscle atrophy or wasting claim 1 , fat loss claim 1 , and/or reduced WAT claim 1 , the method comprising the administration of the compound of formula (I) as per claim 1 , optionally in a pharmaceutical composition that includes a pharmaceutically acceptable excipient claim 1 , to a subject in need of such a treatment or prevention.17. The method of wherein said lipase is ATGL.19. The ...

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22-08-2013 дата публикации

Zwitterionic lipids

Номер: US20130216607A1
Принадлежит: UNIVERSITY OF CALIFORNIA

In various embodiments, the present invention provides zwitterionic lipids, encapsulants incorporating these zwitterionic lipids and such encapsulants encapsulating one or more bioactive agent. An exemplary bioactive agent is a nucleic acid. Also provided are pharmaceutical formulations of the encapsulants and methods of using such formulations to deliver a bioactive agent to a subject in treating or diagnosing disease in that subject.

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22-08-2013 дата публикации

Non-Natural Amino Acids

Номер: US20130217632A1
Автор: Dix Thomas A.

This invention relates in one aspect to non-natural desamino alkyl amino acid compounds, methods of making these compounds, and peptides containing these compounds. In one embodiment, the peptide is neurotensin (8-13) in which the N-terminus is an alpha-desamino, alpha-methyl-N,N-dimethyl-homolysine residue of the invention. 157-. (canceled)59. The compound of claim 58 , wherein the compound is a compound of Formula (I) and the stereochemistry at Cα is S.60. The compound of claim 58 , wherein the compound is a compound of Formula (I) and R claim 58 , R claim 58 , and Rare independently H or methyl.61. The compound of claim 58 , wherein the compound is a compound of Formula (I) and R is methyl.62. The compound of claim 58 , wherein the compound is:a compound of Formula (I), wherein n is 3, 4 or 5;a compound of Formula (II), wherein n is 2, 3, 4 or 5, and z is 2, 3 or 4;a compound of Formula (III), wherein n is 2, 3, 4 or 5, and z is z is 2, 3 or 4 ora compound of Formula (IV), wherein n is 2, 3 or 4.63. The compound of claim 58 , wherein the compound is selected from the group consisting of compounds 22-43 recited in Scheme 2.64. The compound of claim 58 , wherein the compound is a compound of Formula (I) and the protecting group is BOC (t-butoxy carbonyl) claim 58 , FMOC (fluorenylmethoxycarbonyl) claim 58 , Alloc (allyloxycarbonyl) claim 58 , CBZ (benzyloxycarbonyl) claim 58 , Pbf (2 claim 58 ,2 claim 58 ,4 claim 58 ,6 claim 58 ,7-pentamethyl-dihydrobenzofuran-5-sulfonyl) claim 58 , NO(nitro) claim 58 , Pmc (2 claim 58 ,2 claim 58 ,5 claim 58 ,7 claim 58 ,8-pentamethylchroman-6-sulfonyl) claim 58 , Mtr (4-methoxy-2 claim 58 ,3 claim 58 ,6-trimethylbenzenesulfonyl) claim 58 , or Tos (tosyl).66. The peptide of claim 65 , wherein the peptide is a known peptide claim 65 , further wherein the residue is covalently coupled through an amide bond to the N-terminus amine group of the known peptide claim 65 , a substitute for its corresponding analogous natural amino acid ...

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22-08-2013 дата публикации

Compounds and Compositions for the Treatment of Cancer

Номер: US20130217645A1
Принадлежит: PROMETIC BIOSCIENCES INC.

New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of a combination of two of these compounds is described and the use of the combination of one of these compounds with an anticancer agent such as decarbazine, doxorubicin, daunorubicin, cyclophosphamide, busulfex, busulfan, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin and chlorambucil. 130-. (canceled)37. The method of claim 31 , wherein the pharmaceutically acceptable salt is a base addition salt.38. The method of claim 37 , wherein the base addition salt comprises a metal counterion selected from sodium claim 37 , potassium claim 37 , magnesium claim 37 , calcium and lithium.39. The method of claim 38 , wherein the metal counterion is sodium.41. The method of claim 40 , wherein the compound is Compound I claim 40 , II claim 40 , VIII claim 40 , XIII claim 40 , XV claim 40 , XVII claim 40 , XVIII claim 40 , XIX or XX.42. The method of claim 40 , wherein the compound is Compound I claim 40 , II claim 40 , XV claim 40 , XVII or XIX.43. The method of claim 31 , wherein said subject is a human patient.44. The method of claim 31 , wherein the cancer is bladder cancer claim 31 , breast cancer claim 31 , colorectal cancer claim 31 , kidney cancer claim 31 , melanoma claim 31 , non-Hodgkin's lymphoma claim 31 , leukemia claim 31 , ovarian cancer claim 31 , pancreatic cancer claim 31 , prostate cancer or uterine cancer.45. The method of claim 31 , wherein the cancer is breast cancer claim 31 , colorectal cancer claim 31 , leukemia cancer claim 31 , melanoma cancer or pancreatic cancer.46. The method of claim 31 , wherein the compound is used in combination with an anticancer agent.47. The method of claim 46 , wherein ...

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22-08-2013 дата публикации

PHENOXY DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR MODULATORS

Номер: US20130217651A1
Принадлежит: ALLERGAN, INC.

The present invention relates to novel phenoxy derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors. 2. A compound according to wherein Lis CH.3. A compound according to wherein Lis CH.4. A compound according to wherein a is 1 claim 1 , 2 or 3.8. A compound according to selected from:3-[(4-{[5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyl]oxy}benzyl)amino]propanoic acid;3-({4-[3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)butoxy]benzyl}amino)propanoic acid;{3-[(4-{[5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyl]oxy}benzyl)amino]propyl}phosphonic acid;[3-({4-[3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)butoxy]benzyl}amino) propyl]phosphonic acid;3-[(4-{[4-(3,5-difluorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)amino]propanoic acid;3-[(4-{[4-(3-chlorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)amino]propanoic acid;{3-[(4-{[4-(3,5-difluorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)amino]propyl}phosphonic acid;{3-[(4-{[4-(3-chlorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)amino]propyl}phosphonic acid;3-[(4-{[5-(3,4-dimethylphenyl)-4-(3-thienyl)pentyl]oxy}benzyl)amino]propanoic acid;3-[(4-{[5-(3,4-dimethylphenyl)-4-(3-thienyl)pentyl]oxy}benzyl)amino]propyl}phosphonic acid; and3-[(4-{[4-(2,3-difluorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)amino]propanoic acid.9. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound according to and a pharmaceutically acceptable adjuvant claim 1 , diluents or carrier.10. A pharmaceutical composition according to wherein the compound is selected from:3-[(4-{[5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyl]oxy}benzyl)amino]propanoic acid;3-({4-[3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)butoxy]benzyl}amino)propanoic acid;{3-[(4-{[5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyl]oxy}benzyl)amino]propyl}phosphonic acid;[3-({4-[3-(3-chlorophenyl)-4-(3,4- ...

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29-08-2013 дата публикации

METHOD FOR PRODUCING CRYSTALLINE 5-AMINOSALICYLIC ACID

Номер: US20130225539A1
Принадлежит: PharmaZell GmbH

The invention relates to a method for producing crystalline 5-aminosalicylic acid with a particularly high tap and/or bulk density. 1. 5-Aminosalicylic acid (5-ASA) , characterized by having a bulk density of from 300 g/l to 700 g/l and grain size distribution of X(10)=1 μm-30 μm , X(50)=15 μm-60 μm , X(90)=35 μm-220 μm.2. 5-Aminosalicylic acid (5-ASA) according to claim 1 , characterized by a tapped density of from 510 g/l to 900 g/l.3. A process for producing the crystalline 5-aminosalicylic acid (5-ASA) as defined in comprising the following steps:(i) crystallizing 5-ASA from an aqueous solution of 5-ASA with or without the addition of protic or aprotic polar solvents in a concentration range of from 0 to 100% at a temperature of from 25° C. to 150° C. and at a pH-value of from 3.0 to 5.0 to form a suspension of 5-ASA; and(ii) wet grinding the suspension in a homogenizer.4. The process according to claim 3 , characterized in that said crystallizing is effected at a temperature of from 60° C. to 120° C.5. The process according to claim 3 , characterized by comprising a further step (iii) of cooling the suspension.6. The process according to claim 3 , characterized by comprising a further step (iv) of separating the 5-ASA crystals from the mother liquor.7. The process according to claim 3 , characterized by comprising a further step (v) of drying the 5-ASA crystals.8. Dosage articles selected from the group consisting of suppositories claim 1 , enemas claim 1 , sachets with micropellets and tablets comprising the 5-aminosalicylic acid (5-ASA) according to .9. Use of the 5-aminosalicylic acid (5-ASA) according to for preparing a dosage form selected from the group consisting of suppositories claim 1 , enemas claim 1 , sachets with micropellets and tablets.10. A pharmaceutical composition comprising the 5-aminosalicylic acid (5-ASA) according to .11. The 5-aminosalicylic acid as defined in for use in therapy and prophylaxis of a disease selected from the group ...

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29-08-2013 дата публикации

Phenylketone Carboxylate Compounds and Pharmaceutical Uses Thereof

Номер: US20130225681A1
Принадлежит: PROMETIC BIOSCIENCES INC.

Phenylketone carboxylate compounds of Formula I, wherein n=2-6; R═C(0); —OC(O)— or —CH(OH)—; A is (CH2)mCOOH, W(CH2)mCOOH or YCH(COOH)((CH2)pCH3) when B is Ft B is (CH2)mCOOH, W(CH2)mCOOH or YCH(COOH)((CH2)pCH3) when A is Ft or A and B form a 5-7 membered cycloalkyl substituted with COOFt W=0, S or NFt Y=0,S,NH or CH2; m=0-2; p=1-7; have been prepared. These compounds and their pharmaceutically acceptable salts have beneficial therapeutic effects to prevent or treat a condition related to (l) blood disorders, (ii) inflammation related diseases, (iii) renal disorders and/or renal disorders complications, or (iv) fibrosis-related organ dysfunction. 124-. (canceled)26. The compound of claim 25 , wherein R is —C(O)—.27. The compound of claim 25 , wherein p is 3-7.28. The compound of claim 25 , wherein the salt is a base addition salt.29. The compound of claim 28 , wherein the base addition salt comprises a metal counterion selected from sodium claim 28 , potassium claim 28 , magnesium claim 28 , calcium and lithium.30. The compound of claim 29 , wherein the metal counterion is calcium.32. The compound of claim 31 , wherein the compound is Compound I claim 31 , III or X.33. A pharmaceutical composition comprising a compound according to claim 25 , and a pharmaceutically acceptable carrier.34. A method for the prevention or treatment of: (i) a blood disorder claim 25 , (ii) an inflammation-related disease claim 25 , (iii) a renal disorder or a renal disorder complication claim 25 , or (iv) a fibrosis-related organ dysfunction wherein said method comprises administering claim 25 , to a patient in need of such treatment claim 25 , a compound of .35. The method of claim 34 , wherein the blood disorder is anemia or neutropenia.36. The method of claim 34 , wherein said method stimulates erythropoiesis and/or hematopoiesis in the subject.37. The method of claim 34 , wherein the renal disorder is a nephropathy.38. The method of claim 34 , used for nephroprotection of a subject ...

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29-08-2013 дата публикации

IMAGING AGENTS

Номер: US20130225828A1
Автор: Goodman Mark M.
Принадлежит: EMORY UNIVERSITY

The present invention provides novel amino acid compounds useful in detecting and evaluating brain and body tumors. These compounds have the advantageous properties of rapid uptake and prolonged retention in tumors and can be labeled with halogen isotopes such as fluorine-18, iodine-123, iodine-124, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77, bromine-82, astatine-210, astatine-211, and other astatine isotopes. These compounds can also be labeled with technetium and rhenium isotopes using known chelation complexes. The compounds disclosed herein bind tumor tissues in vivo with high specificity and selectivity when administered to a subject. Preferred compounds show a target to non-target ratio of at least 2:1, are stable in vivo and substantially localized to target within 1 hour after administration. Preferred compounds include 1-amino-2-[F]fluorocyclobutyl-1-carboxylic acid (2-[F]FACBC) and 1-amino-2-[]fluoromethylcyclobutyl-1-carboxylic acid (2-[F]FMACBC). The labeled amino acid compounds of the invention are useful as imaging agents in detecting and/or monitoring tumors in a subject by PET or SPECT. 2. The compound of claim 1 , wherein halo is a non-radioactive F claim 1 , Cl claim 1 , Br claim 1 , or I.3. The compound of claim 1 , wherein (CRR)is CH.4. The compound of claim 1 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Ris t-butyl.6. The compound of claim 1 , wherein Ris acyl.7. The compound of claim 6 , wherein acyl is t-butoxycarbonyl.8. A compound di-tert-butyl 2-oxa-3-thia-4-azabicyclo[3.2.0]heptane-4 claim 6 ,5-dicarboxylate 3 claim 6 ,3-dioxide.9. A kit comprising a compound of and a radio isotope labeling reagent.10. The kit of wherein the compound is di-tert-butyl 2-oxa-3-thia-4-azabicyclo[3.2.0]heptane-4 claim 9 ,5-dicarboxylate 3 claim 9 ,3-dioxide.11. The kit of claim 9 , wherein the radio isotope labeling reagent is salt of F. This application is a divisional of U.S. patent application Ser. No. 12/946,027 filed Nov. 15 ...

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29-08-2013 дата публикации

Method To Prepare beta-Functionalized Aliphatic Esters

Номер: US20130225852A1
Принадлежит: Cognis IP Management GmbH

The invention pertains to a new route to prepare β-functionalized carboxylic acid esters in a one-pot reaction, by reacting an olefinic acid ester in the presence of a catalyst system, comprising a Rh(I)-complex, together with an aryl boron or a diamine as nucleophilic compounds, and under oxygen-free conditions and elevated temperatures.

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05-09-2013 дата публикации

ROS-Activated Compounds as Selective Anti-Cancer Therapeutics

Номер: US20130230542A1
Принадлежит:

Provided are compounds according to the following Formula I: 2. The compound according to claim 1 , wherein said alkyl claim 1 , aryl claim 1 , and aralkyl substitutions are selected from the group consisting of alkoxyl claim 1 , halo claim 1 , OH claim 1 , CN claim 1 , carboxyl claim 1 , carboxyl ester claim 1 , and substituted or unsubstituted alkyl.3. The compound according to claim 1 , wherein Ris H or alkyl when Ris aryl or aralkyl claim 1 , and wherein Ris H or alkyl when Ris aryl or aralkyl.4. The compound according to claim 1 , wherein Rand Rare each independently selected from the group consisting of H claim 1 , substituted or unsubstituted C-Calkyl claim 1 , and substituted or unsubstituted phenyl; and Ris OH.5. The compound according to claim 1 , wherein the cancer is associated with production of elevated reactive oxygen species.6. The compound according to claim 5 , wherein the cancer is selected from the group consisting of leukemia claim 5 , renal cancer claim 5 , and cancers of the central nervous system.7. The compound according to claim 6 , wherein the leukemia is selected from the group consisting of acute myeloid leukemia claim 6 , acute lymphoblastic leukemia claim 6 , plasmacytoma claim 6 , myeloma claim 6 , myelogenous leukemia claim 6 , acute lymphocytic leukemia claim 6 , acute promyelocytic leukemia claim 6 , and multiple myeloma.9. A method of reducing proliferative capacity in a cell claim 1 , the method comprising contacting the cell with an effective amount of a compound according to .10. The method according to claim 9 , wherein the cell is a mammalian cell.11. The method according to claim 10 , wherein the cell is a cancer cell.12. A method of treating a cancer associated with elevated ROS comprising administering to a subject in need thereof an effective amount of a compound according to .13. The method according to claim 12 , wherein the subject is a mammal.14. The method according to claim 13 , wherein the cancer is selected from ...

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05-09-2013 дата публикации

Enhanced bioavailable iodine molecules

Номер: US20130230619A1
Автор: Peter A. Stark
Принадлежит: Zinpro Corp

This invention relates to supplementation of the diets of domesticated animals (livestock and poultry) with iodine in an enhanced bioavailable manner, that is to say the iodine is more available to the animal than when using conventional sources of iodine, such as calcium iodate. The supplementary compound are alpha amino acid metal iodide complexes.

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05-09-2013 дата публикации

SYNTHESIS, METHODS OF USING, AND COMPOSITIONS OF CYCLOALKYLMETHYLAMINES

Номер: US20130231386A1
Принадлежит: Reviva Pharmaceuticals, Inc.

The present invention provides novel cycloalkylmethylamine analogs, and methods of preparing cycloalkylmethylamine analogs. The present invention also provides methods of using cycloalkylmethylamine analogs and compositions of cycloalkylmethylamine analogs. The pharmaceutical compositions of the compounds of the present invention can be advantageously used for treating and/or preventing obesity and obesity related co-morbid indications. 2. The cycloalkylmethylamine derivative of claim 1 , wherein SP is alkylene.3. The cycloalkylmethylamine derivative of claim 1 , wherein SP is a direct bond.4. The cycloalkylmethylamine derivative of claim 2 , wherein X is O.5. The cycloalkylmethylamine derivative of claim 3 , wherein X is O.6. The cycloalkylmethylamine derivative of claim 2 , wherein X is NH.7. The cycloalkylmethylamine derivative of claim 3 , wherein X is NH.8. The cycloalkylmethylamine derivative of claim 1 , wherein Ris H.9. The cycloalkylmethylamine derivative of claim 1 , wherein Ris H or alkyl.10. The cycloalkylmethylamine derivative of claim 1 , wherein Ris alkoxy.11. The cycloalkylmethylamine derivative of claim 1 , wherein Ris halogen.12. The cycloalkylmethylamine derivative of claim 1 , wherein Ris alkyl or substituted alkyl.13. The cycloalkylmethylamine derivative of claim 1 , wherein Ris H or alkyl.14. The cycloalkylmethylamine derivative of claim 1 , wherein Ris alkoxy or halogen.15. The cycloalkylmethylamine derivative of claim 1 , wherein Ris ethyl claim 1 , n-propyl claim 1 , iso-propyl or n-butyl claim 1 , s-butyl claim 1 , or t-butyl.18. A method of treating obesity claim 2 , comprising administering to a subject the cycloalkylmethylamine derivative according to .19. A method of treating obesity claim 3 , comprising administering to a subject the cycloalkylmethylamine derivative according to .20. A method of treating depression claim 1 , comprising administering to a subject the cycloalkylmethylamine derivative according to . This application is a ...

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12-09-2013 дата публикации

4-SUBSTITUTED-3-BENZYLOXY-BICYCLO[3.1.0]HEXANE COMPOUNDS AS mGluR 2/3 ANTAGONISTS

Номер: US20130237573A1
Принадлежит: Eli Lilly and Co

A mGlu2/3 receptor antagonist of the formula: its uses, and methods for its preparation are described.

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19-09-2013 дата публикации

Calcium-sensing receptor-active compounds

Номер: US20130244995A1
Принадлежит: Leo Pharma AS

Compounds of general formula (I), their use as calcium receptor-active compounds for the prophylaxis, treatment or amelioration of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism, pharmaceutical compositions comprising said compounds, and methods of treating diseases with said compounds.

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19-09-2013 дата публикации

Intermediate compounds and processes for the preparation of quinoline derivatives such as laquinimod sodium

Номер: US20130245065A1
Принадлежит: Mapi Pharma Ltd

The present invention relates to processes for the preparation of quinoline-3-carboxamide derivatives, such as sodium 5-chloro-3-(ethylphenylcarbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-olate (Laquinimod sodium). The present invention further relates to intermediates formed in such processes.

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19-09-2013 дата публикации

Novel compound and medical use thereof

Номер: US20130245074A1
Автор: Koji Yano, Masaya Kokubo
Принадлежит: Ono Pharmaceutical Co Ltd

Provided is a levodopa prodrug that overcomes the problems attributed to the blood kinetics of levodopa such as large number of doses and the incidence of side effects due to frequent dosing. (2S)-2-Amino-3-(3,4-bis((2-(benzoyloxy)-2-methylpropanoyl)oxy)phenyl)propanoic acid, a salt thereof, or a solvate thereof is a levodopa prodrug, and provides a flat blood concentration-time profile of levodopa through oral administration, and therefore is useful as a preventive and/or therapeutic agent for Parkinson's disease and/or Parkinson's syndrome that overcomes the problems associated with pharmaceutical preparations of levodopa.

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19-09-2013 дата публикации

AMINO ACID DERIVATIVES AND ABSORBABLE POLYMERS THEREFROM

Номер: US20130245133A1
Автор: Bezwada Rao S.
Принадлежит: Bezwada Biomedical, LLC.

The present invention relates to the discovery of new class of hydrolysable amino acid derivatives and absorbable polyester amides, polyamides, polyepoxides, polyureas and polyurethanes prepared therefrom. The resultant absorbable polymers are useful for drug delivery, tissue engineering, tissue adhesives, adhesion prevention, bone wax formulations, medical device coatings, stents, stent coatings, highly porous foams, reticulated foams, wound care, cardiovascular applications, orthopedic devices, surface modifying agents and other implantable medical devices. In addition, these absorbable polymers should have a controlled degradation profile. 2. A surgical article or component thereof or polymeric carrier comprising a polymer made of the isocyanate of claim 1 , which is a stent claim 1 , stent coating claim 1 , wound covering claim 1 , burn covering claim 1 , foam claim 1 , highly porous foams claim 1 , reticulated foams claim 1 , tissue engineering scaffold claim 1 , film claim 1 , adhesion prevention barrier claim 1 , implantable medical device claim 1 , controlled drug delivery system claim 1 , suture claim 1 , ligature claim 1 , needle and suture combination claim 1 , surgical clip claim 1 , surgical staple claim 1 , surgical prosthesis claim 1 , textile structure claim 1 , coupling claim 1 , tube claim 1 , support claim 1 , screw claim 1 , pin claim 1 , bone wax formulation claim 1 , tissue adhesive or an adhesion prevention barrier.3. A surgical article or component thereof of claim 2 , wherein a biologically active agent is physically embedded or dispersed into the polymer matrix of the controlled delivery system.4. A pharmaceutical composition comprising a polymeric carrier of and a drug uniformly dispersed therein.5. A polymer containing surgical article or component thereof or polymeric carrier which is a stent claim 1 , stent coating claim 1 , wound covering claim 1 , burn covering claim 1 , foam claim 1 , highly porous foam claim 1 , reticulated foam ...

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19-09-2013 дата публикации

Unnatural Reactive Amino Acid Genetic Code Additions

Номер: US20130245230A1
Принадлежит: Scripps Research Institute

This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

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19-09-2013 дата публикации

Processes for preparing benzimidazole compounds

Номер: US20130245279A1
Принадлежит: Array Biopharma Inc, AstraZeneca AB

Provided are processes for the preparation of benzimidazole structures having Formula VIIIb-1: and salts and solvates thereof, wherein Z, X 5 , R 2b , R 2c and R 10 are as defined herein. Compounds of Formula VIIIb-1 are useful for the preparation of benzimidazole derivatives.

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26-09-2013 дата публикации

Complex of divalent metal cations and chelating agent

Номер: US20130247630A1
Принадлежит: Akzo Nobel Chemicals International BV

The present invention relates to a complex of two divalent metal cations and a chelating agent chosen from the group of EDDHA (ethylenediamine-N,N′-di-(hydroxyphenyl acetic acid)), EDDHMA (ethylenediamine-N,N′-di-(hydroxy-methylphenyl acetic acid)), and HBED(N,N′-bis(hydroxybenzyl)ethylenediamine-N,N′-diacetic acid), a process to prepare such complex, plant nutrition compositions containing such complex and the use thereof as an algaecide, a bactericide, a herbicide, an insecticide, a molluscicide, a virucide or a fungicide, other than a fungicide or bactericide used for personal care.

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26-09-2013 дата публикации

METHOD OF DROXIDOPA SYNTHESIS

Номер: US20130253061A1
Принадлежит: CHELSEA THERAPEUTICS, INC.

The present application relates to a novel method of preparing L-threo-dihydroxyphenylserine (droxidopa). Specifically, the application is directed to a method of preparing droxidopa via a deprotection step that is an alternative to deprotection steps that have been previously disclosed. The new deprotection strategy is advantageous in that it avoids the need to use hydrogenolysis or hydrazine. 1. A method for the preparation of droxidopa comprising the step of deprotecting a droxidopa precursor comprising an N-phthaloyl group in the absence of hydrazine to form droxidopa free of residual hydrazine.2. The method of claim 1 , wherein the deprotecting step comprises treating N-phthaloyl-3-(3 claim 1 ,4-dihydroxyphenyl)serine with hydroxylamine.3. The method of claim 1 , wherein the droxidopa is enantomerically enriched for the L-threo isomer.4. The method of claim 3 , wherein the L-threo isomer is present at an optical purity of at least about 98%.6. The method of claim 5 , wherein step a) comprises adding glycine in the presence of a base.7. The method of claim 6 , wherein the base is sodium hydroxide or potassium hydride.8. The method of claim 5 , wherein step a) is conducted in an alcohol solvent.9. The method of claim 8 , wherein the alcohol solvent is methanol or ethanol.10. The method of claim 5 , wherein step b) comprises adding a phthaloylating agent selected from the group consisting of phthalic acid claim 5 , phthaloyl chloride claim 5 , phthalic anhydride claim 5 , N-carbomethoxy pthalimide claim 5 , N-carbethoxy pththalimide claim 5 , monomethylphthalate claim 5 , monoethyl phthalate claim 5 , dimethyl phthalate claim 5 , diethyl phthalate claim 5 , and diphenyl pththalate.11. The method of claim 10 , wherein the method further comprises the step of reacting phthalimide with ClCOOMe to give N-carbomethoxy phthalimide.12. The method of claim 11 , wherein step b) comprises reacting the free amine with N-carbomethoxy phthalimide in the presence of NaCO.13. ...

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03-10-2013 дата публикации

CRYSTALLINE FORMS OF (R)-3-[N-(3'-CHLOROBIPHENYL-4-YLMETHYL)-N'-(3-HYDROXYISOXAZOLE-5-CARBONYL)HYDRAZINO]-2-HYDROXYPROPIONIC ACID ISOPROPYL ESTER

Номер: US20130259897A1
Принадлежит:

The invention provides crystalline forms of (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′—(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester. This invention also provides pharmaceutical compositions comprising the crystalline compound, processes and intermediates for preparing the crystalline compound, and methods of using the crystalline compound to treat diseases. 1. A crystalline (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′—(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester , selected from:a neutral monohydrate Form 1 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.26±0.20, 14.68±0.20, 15.64±0.20, 16.36±0.20, 18.52±0.20, 20.40±0.20, 21.08±0.20, 21.48±0.20, 21.68±0.20, 23.18±0.20, 24.50±0.20, 24.80±0.20, 25.34±0.20, and 26.56±0.20;a neutral Form 2 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.48±0.20, 8.02±0.20, 9.38±0.20, 12.24±0.20, 14.86±0.20, 18.72±0.20, 20.94±0.20, 21.34±0.20, 22.32±0.20, and 24.68±0.20;a neutral solvated Form 2′ characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.26±0.20, 8.05±0.20, 12.20±0.20, 14.48±0.20, 15.84±0.20, 16.22±0.20, 18.78±0.20, 20.60±0.20, 21.29±0.20, 21.74±0.20, 23.10±0.20, 24.16±0.20, and 24.44±0.20;a neutral anhydrous Form 3 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.12±0.20, 8.86±0.20, 11.92±0.20, 13.68±0.20, 16.10±0.20, 18.12±0.20, 18.46±0.20, 19.06±0.20, 19.48±0.20, 20.60±0.20, 21.28±0.20, 24.46±0.20, 25.94±0.20, and 26.40±0.20;a neutral anhydrous Form 4 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.70±0.20, 13.00±0.20, 16.00±0.20, 16.94±0.20, 17.36±0.20, 18.72±0.20, 19.00±0.20, 19.78±0.20, 20.24±0.20, 21.70±0.20, 23.68±0.20, and 27.94±0.20;a tromethamine salt characterized by a powder x-ray diffraction pattern ...

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03-10-2013 дата публикации

Compounds and methods for delivery of prostacyclin analogs

Номер: US20130261187A1
Автор: David Mottola, Ken Phares
Принадлежит: United Therapeutics Corp

This invention pertains generally to prostacyclin analogs and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. Generally, the compounds and methods of the present invention increase the oral bioavailability and circulating concentrations of treprostinil when administered orally. Compounds of the present invention have the following formula:

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03-10-2013 дата публикации

GENETICALLY ENCODED INITIATOR FOR POLYMER GROWTH FROM PROTEINS

Номер: US20130261259A1
Принадлежит: FRANKLIN AND MARSHALL COLLEGE

This invention pertains to methods for producing homogeneous recombinant proteins that contain polymer initiators at defined sites. The unnatural amino acid, 4-(2′-bromoisobutyramido)phenylalanine of formula 1, was designed and synthesized as a molecule comprising a functional group further comprising an initiator for an atom-transfer radical polymerization (‘ATRP”) that additionally would provide a stable linkage between the protein and growing polymer. We evolved a (Mj) tyrosyl-tRNA synthetase/tRNApair to genetically encode this unnatural amino acid in response to an amber codon. To demonstrate the utility of this functional amino acid, we produced Green Fluorescent Protein with the unnatural amino acid initiator of formula 1 site-specifically incorporated on its surface (GFP-1). Purified GFP-1 was then used as an initiator under standard ATRP conditions with oligo(ethylene oxide)monomethyl ether methacrylate, efficiently producing a polymer-GFP bioconjugate wherein the polymer is connected at a specifically selected site on GFP. 2. The compound of claim 1 , as described by formula 6 claim 1 , wherein R1 and R2 are independently H claim 1 , methyl claim 1 , or phenyl; X is F claim 1 , Cl claim 1 , Br claim 1 , I; or N; A is O claim 1 , S claim 1 , or NR claim 1 , wherein R is H claim 1 , methyl claim 1 , or phenyl; n is 1; or a salt thereof.6. The compound of claim 1 , wherein R1 and R2 are independently H claim 1 , methyl claim 1 , or phenyl; X is F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , or N; A is O claim 1 , S claim 1 , or NR claim 1 , wherein R is H claim 1 , methyl claim 1 , or phenyl; n is 0; or a salt thereof.14. The method of claim 13 , wherein R1 and R2 are independently H claim 13 , methyl claim 13 , or phenyl; X is F claim 13 , Cl claim 13 , Br claim 13 , I claim 13 , or N; Y is F claim 13 , Cl claim 13 , Br claim 13 , I claim 13 , or trifluoroacetate; A is O claim 13 , S claim 13 , or NR claim 13 , wherein R is H claim 13 , methyl claim 13 , ...

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03-10-2013 дата публикации

PROCESS FOR THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID

Номер: US20130261298A1
Принадлежит: LES LABORATOIRES SERVIER

Process for the synthesis of ivabradine of formula (I): 2. The process according to claim 1 , wherein the coupling agent used to carry out the reaction for lactamisation of the compound of formula (VI) is selected from oxalyl chloride claim 1 , thionyl chloride claim 1 , N claim 1 ,N-dicyclohexylcarbodiimide (DCC) claim 1 , 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) claim 1 , N claim 1 ,N-carbonyldiimidazole (CDI) claim 1 , 1-propanephosphonic acid cyclic anhydride (T3P) and 1-(methylsulphonyl)-1H-benzotriazole.3. The process according to claim 2 , wherein the coupling agent used to carry out the reaction for lactamisation of the compound of formula (VI) is thionyl chloride.4. The process according to claim 3 , wherein the amount of thionyl chloride used to carry out the reaction for lactamisation of the compound of formula (VI) is between 1 and 5 equivalents claim 3 , inclusive.5. The process according to claim 1 , wherein the base used to carry out the reaction for lactamisation of the compound of formula (VI) is selected from triethylamine claim 1 , diisopropylethylamine and pyridine.6. The process according to claim 5 , wherein the base used to carry out the reaction for lactamisation of the compound of formula (VI) is triethylamine.7. The process according to claim 1 , wherein the organic solvent used to carry out the reaction for lactamisation of the compound of formula (VI) is selected from dichloromethane claim 1 , tetrahydrofuran claim 1 , acetonitrile claim 1 , acetone and toluene.8. The process according to claim 7 , wherein the organic solvent used to carry out the reaction for lactamisation of the compound of formula (VI) is dichloromethane.9. The process according to claim 1 , wherein the reaction for lactamisation of the compound of formula (VI) is carried out at a temperature between 0° C. and 40° C. claim 1 , inclusive.12. The process according to claim 10 , wherein the base used to carry out the alkylation reaction between the compound of ...

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03-10-2013 дата публикации

PREPARATION OF ORGANIC COMPOUNDS FOR ENHANCED REACTIVITY

Номер: US20130261332A1
Автор: Latham Keith R.
Принадлежит:

The present invention provides an improved method for preparing, purifying, precipitating, etc., a subject compound for use in a subsequent reaction carried out in suspension. The present invention relies on a precipitating solvent being added to an aqueous solution comprising the subject compound to form a precipitate of the subject compound, which may be further dried and/or purified. Compositions made according to present methods have improved characteristics and properties, such as increased surface and/or reduced density, resulting in a higher reactivity in a subsequent reaction carried out in suspension. 1. A method , comprising the following steps:(a) dissolving a starting form of a subject compound into an aqueous solvent to form an aqueous solution; and(b) adding a precipitating solvent to the aqueous solution to form a precipitate of the subject compound,wherein step (b) is performed after step (a), wherein the precipitating solvent is miscible in the aqueous solvent, and wherein the precipitate of the subject compound has a surface area per unit of mass that is greater than the surface area per unit of mass of the starting form of the subject compound.2. The method of claim 1 , wherein the precipitate of the subject compound has a surface area per unit of mass that is at least 2-fold greater than the surface area per unit of mass of the starting form of the subject compound.3. The method of claim 1 , wherein the precipitate of the subject compound has a surface area per unit of mass that is at least 5-fold greater than the surface area per unit of mass of the starting form of the subject compound.4. The method of claim 1 , wherein the precipitate of the subject compound has a surface area per unit of mass that is at least 20-fold greater than the surface area per unit of mass of the starting form of the subject compound.5. (canceled)6. The method of claim 1 , wherein the precipitate of the subject compound has a surface area per unit of mass that is about ...

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