О-ЭТИЛФОСФИТ N,N-ДИМЕТИЛ-[3-(ПРОПОКСИКАРБОНИЛАМИНО)ПРОПИЛ]АММОНИЯ, ОБЛАДАЮЩИЙ ФУНГИЦИДНОЙ АКТИВНОСТЬЮ

Изобретение относится к новому соединению, проявляющему фунгицидную активность. Описывается соединение О-этилфосфит-N,N-диметил-[3-(пропоксикарбониламино)пропил] аммония, имеющее структуру I. Вышеуказанное соединение проявляет активность против заболевания растений, вызываемых микроорганизмами Phycomycete, таких как ложная мучнистая роса, различные виды гнили томатов или картофеля. 1 табл.

АМИНОБЕНЗОФЕНОНЫ

Изобретение относится к новым производным аминобензофенонов общей формулы I, обладающих свойствами ингибитора интерлейкина-1β(IL-1β) и фактора некроза опухоли(ТМР-α). Соединения могут найти применение для получения лекарственного средства для лечения и профилактики заболеваний, связанных с регулирующей системой цитокинов, таких как воспалительные заболевания. Изобретение также относится к фармацевтическим композициям и применению. В общей формуле I ! ! Х является кислородом; R1 является (C1-C3)алкилом, R2 является одним или более, одинаковыми или разными заместителями, выбранными из группы, включающей водород и галоген; R3 является одним или более, одинаковыми или разными заместителями, выбранными из группы, включающей водород и галоген, R4 является водородом, R5 является водородом, R6 является (C1-C10)алкил-гетероциклилом, (C1-C10)алкилом, (C2-C10)олефиновой группой, гетероциклилом, Y1R21, Y2R22 или Y4R24; где (C1-C10)алкил, (C2-C10)олефиновая группа замещены одним или более одинаковыми ...

ЗАМЕЩЕННЫЕ ГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описываются новые замещенные гетероциклические соединения формулы I, где А означает двухвалентный радикал, выбранный из -О-СО-, -CH2O-CO- и др., как указано в п.1 формулы, R1 означает водород или C1-C4-алкил; m - 2, 3; Ar1 означает фенил, возможно замещенный галогеном, гидроксилом, C1-C4-алкокси, C1-C4-алкилом, трифторметилом, метилендиокси; Т означает -CH2-Z, -CH(C6H5 )2, -C(C6H5)3. Соединения формулы I обладают сродством к рецепторам тахикинина при ингибиторной константе Ki ниже 10-8 М. Описывается способ получения соединений формулы I и промежуточные соединения, используемые в нем. Описывается также фармацевтическая композиция, обладающая антагонистической активностью к рецепторам нейрокининов, содержащая в качестве активного вещества соединение формулы I. 12 с. и 13 з.п.ф-лы, 3 табл.

ПРОИЗВОДНЫЕ ГЛИЦЕРИНА, СРЕДСТВО ДЛЯ ДОСТАВКИ ФИЗИОЛОГИЧЕСКИ АКТИВНОГО ВЕЩЕСТВА И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Целью изобретения является создание липидного средства, функционально эквивалентного, так называемой, катионной липосоме, менее токсичного и содержащего липид или его аналог в качестве компонента этого средства. Соединения изобретения относятся к соединениям общей формулы I, где R1 и R2 неодинаковы и каждый представляет группу -0-Y или группу - А-(СН2)n-Е, где n-целое число от 2 до 4, E представляет пирролидино, пиперидино, морфолино и др. или Е представляет группу где R3 и R4-одинаковые или различные и каждый представляет атом водорода, низший-С1 - С4-алкил, гидроксинизший- С1 - С4-алкил; А представляет группы формулы R и Y - одинаковы и каждый представляет олеил, или олеоил, или пальмитоил при условии, что когда n = 1, то А не может быть группой и . Средство для доставки физиологически активного вещества, содержащее фосфолипид и модифицирующий компонент, и фармацевтическая композиция, содержащая средство для доставки физиологически активного вещества, физиологически активное вещество ...

КАРБАМАТЫ ФЕНИЛАЛКИЛАМИНОСПИРТОВ И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

... 1. О-кар6амоил-(D/L)-фенилаланинол структурной формулы I и его фармацевтически приемлемые соли. 2. O-карбамоил-(D)-фенилаланинол структурной формулы II и его фармацевтически приемлемые соли. 3. O-карбамоил-(L)-фенилаланинол структурной формулы III и его фармацевтически приемлемые соли. 4. Способ получения O-карбамоил-(D/L)-фенилаланинола структурной формулы I включающий стадии: обработки (D/L)-фенилаланинола структурной формулы IV бензилхлорформиатом в основном водном растворе с образованием N-бензилоксикарбонил-(D/L)-фенилаланинола структурной формулы V осуществления взаимодействия соединения структурной формулы V с фосгеном и затем обработки избытком концентрированного раствора гидроокиси аммония с получением о-карбамоил-N-бензилоксикарбонил(D/L)-фенилаланинола структурной формулы VI удаления защитной группы Y соединения структурной формулы VI путем гидрогенолиза с образованием О-карбамоил-(D/L)-фенилаланинола структурной формулы I. 5. Способ по п. 4, отличающийся тем, что соединения ...

BRENNSTOFF- UND SCHMIERÖLZUSAMMENSETZUNGEN, DIE SEHR LANGKETTIGE ALKYLPHENYL-POLY(OXYALKYLEN)-AMINOCARBAMATE ENTHALTEN.

Hemmer der retroviralen Protease

Inhibitoren retroviraler Proteasen

AROMATISCHE VERBINDUNGEN, DIESE ENTHALTENDE PHARMAZEUTISCHE ZUSAMMENSETZUNGEN UND IHRE THERAPEUTISCHE ANWENDUNG

Carbodiimide und/oder oligomere Polycarbodiimide auf Basis von 1,3-Bis-(1-methyl-1-isocyanatoethyl)-benzol, ein Verfahren zu ihrer Herstellung und ihre Verwendung als Hydrolysestabilisator

VERFAHREN ZUR HERSTELLUNG VON CYANACETYLCARBAMATEN

Verfahren zur Herstellung von Diurethanen und ihre Verwendung zur Herstellung von Diisocyanaten

5-Oxo-dibenzo[a,d]cyclohepta-1,4-diene und ihre Verwendung als retrovirale Mittel

VERFAHREN ZUR HERSTELLUNG VON ISOCYANATGRUPPEN AUFWEISENDEN ALLOPHANATEN

EINTOPFVERFAHREN ZUR HERSTELLUNG VON 2-OXAZOLIDINONDERIVATE

NEUE MANNICHBASEN, EIN VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG BEI DER HERSTELLUNG VON POLYURETHANEN

Compound

CERTAIN NON-TERPENOID JUVENILE HORMONE MIMICKING COMPOUNDS AND THEIR USE IN CONTROLLING INSECTS

... 1385602 1,2 - Bis(alkylthiocarbamoyl)- ethanes STAUFFER CHEMICAL CO 3 May 1973 [26 May 1972] 20974/73 Heading C2C The invention comprises compounds of general formula in which R is C 2 to C 6 alkyl; R 1 is H or C 1 to C 4 alkyl ; R2 is C 1 to C 4 alkyl; and R 3 is C 2 to C 6 alkyl; and their use in controlling insects by hindering or impeding their metamorphosis and reproduction. The compounds may be prepared by the condensation of a diamine of formula with an alkyl chlorothioformate of formula and/or of formula ...

Process for making dialkyl ethylidene dicarbamate

N-(2,6-DISUBSTITUTED PHENYL)-ALKANEDIAMINES

Acetylenic diaminobutane derivatives

Novel acetylenic diamine derivatives are inhibitors of decarboxylase enzymes involved in polyamine formation and have the following general Formula I:- wherein:- Ra and Rb independently represent hydrogen, C2-C5 alkylcarbonyl, phenylcarbonyl, phenyl-(C1-C4 alkyl) carbonyl, or an aminocarboxylic acid residue derived by removal of an hydroxy group from a carboxy moiety of an L-aminocarboxylic acid; and Y represents CH2=CH- or CH IDENTICAL C-.

3-(N-METHYL-N-ALKYLAMINO)-METHOXYMETHYL-PROPANOL DERIVATIVES

Polar-substituted hydrocarbons

Substituted hydroxyethylamines

Amine derivatives of oxo- and hydroxy-substituted hydrocarbons.

The invention provides a new class of hydrazine derivatives of the general formula ...

Retroviral protease inhibitors.

The invention relates to certain retroviral protease inhibitors, ...

Substituted hydroxyethylamines

Polar-substituted hydrocarbons

AMINE DERIVATIVES OF OXO-AND HYDROXY-SUBSTITUTED HYDROCARBONS

Processes and intermediates for preparing benzyl epoxides

Disclosed are intermediates and processes for preparing epoxides of the formual: where R and PROT are defined herein. These epoxides are useful as intermediates in the production of biologically active compounds, i.e., in the production of pharmaceutical agents.

Substituted hydroxyethylamines

Derived from glycerol, a method of preparation of these derivatives and therapeutic compositions the container.

1,4-Diamino-2,3-Dihydroxybutanes.

Substituted hydroxyethylamines.

2-Amino-1, 2, 3, 4-tetahydronaphthalene derivatives active on the cardiovascular system, processes for their preparation and pharmaceutical compositions containing them

“Derived from (N-methyl-NR-ALCOYl) the amino-3 méthoxyméthylène-2 propane 1-o1, a method of preparation of these same compounds and therapeutic compositions the container”.

Processes and intermediates for preparing benzyl substituted epoxides.

Processes and intermediates for preparing benzyl epoxides

Processes and intermediates for preparing benzyl epoxides

AMINE DERIVATIVES OF OXO-AND HYDROXY-SUBSTITUTED HYDROCARBONS

PROCEDURE AND INTERMEDIATE FOR THE PRODUCTION OF RETROVIRALEN PROTEASEHEMMERN

PROCEDURES FOR THE PRODUCTION OF ALKYL N (3 - DIMETHYLAMINO) ALKYLCARBAMATEN

CARBAMATDERIVATE AND AGRICULTURAL/GARDEN-STRUCTURAL BACTERICIDAL ONE

WATER AND OIL-REJECTING OF FLUORINE ACRYLATES

PROCEDURE FOR THE PRODUCTION OF HYDROXYETHYLAMINEN

TAR RNA BINDING PEPTIDE

SPHINGOLIPIDEN

VERFAHREN ZUR HERSTELLUNG VON ALIPHATISCHEN UND/ODER CYCLOALIPHATISCH GEBUNDENEN ISOCYANT- GRUPPEN AUFWEISENDEN ALLOPHANATEN

3-(N-METHYL-N-ALKYL)-AMINO-2-METHOXYMETHYLENPRO AN-1-OL-DERIVATE, VERFAHREN ZU DEREN HERSTELLUNG UND SIE ENTHALTENDE THERAPEUTISCHE ZUSAMMENSETZUNGEN

Tilting pole for marking slalom courses

GLYCERIN DERIVATIVES, PROCEDURES FOR THEIR PRODUCTION AND IT ABSTENTION THERAPEUTIC COMPOSITIONS

PROCEDURE FOR the PRODUCTION OF NEW SUBSTITUTED ONE 3-AMINOALKYLAMINO-2-HYDROXY-1 PHENOXYPROPANEN AND OF THEIR ACID ADDITION SALTS

INTERMEDIATE PRODUCTS AND PROCEDURES FOR THE PRODUCTION OF HEPTAPEPTID OXYTOCINANALOGA

PROCEDURE FOR THE PRODUCTION OF POLYMETHANKUNST MATERIALS

INHIBITORS THAT RETROVIRALEN PROTEASE

RETROVIRALE PROTEASE INHIBITORS

CARBAMIDSÄUREESTER DERIVATIVES, MEANS AND MANUFACTURING PROCESSES

NEW MONOMER COMPONENTS FROM HYDROXYFETTSÄUREN FOR THE PRODUCTION OF PLASTICS.

AROMATIC CONNECTIONS THESE CONTAINING PHARMACEUTICAL COMPOSITIONS AND YOUR THERAPEUTIC USE

HIV PROTEASE HEMMER.

ADDUCTS FROM DIISOCYANATEN AND METHACRYLOYLALKYLETHERN, - ALKOXYBENZOLEN AND/OR ALKOXYCYCLOALKANEN AND THEIR USE.

GROUPS OF URETHANES EXHIBITING DIISOCYANATE, A PROCEDURE FOR YOUR PRODUCTION AND YOUR USE AS BONDING AGENTS AND/OR BONDING AGENT COMPONENT IN PU LACQUERS.

PERFLUORALKYLGRUPPEN, GROUPS DERIVED FROM EPICHLOROHYDRIN AND CONTAINING URETHANES, PROCEDURE FOR YOUR PRODUCTION AND YOUR USE DIALKOHOLRESTE.

DERIVATIVES OF 3-PHENYL-2-PROPENAMIN, YOUR PRODUCTION AND THESE CONTAINING DRUGS.

PROCEDURE FOR THE PRODUCTION OF BESTATIN DERIVATIVES AND THEIR INTERMEDIATE PRODUCTS.

N-2,3-BUTADIENYL-1,4-BUTADIAMIN-DERIVATE.

15-DEOXYSPERGUALINANALOGE CONNECTIONS, PROCEDURES FOR YOUR PRODUCTION AND YOUR USE IN the THERAPY

CIS EPOXIDE OF DERIVATIVES, USABLE AS IRREVERSIBLE ONES HIV PROTEASE INHIBITORS AND PROCEDURES AND INTERMEDIATE PRODUCTS TO YOUR PRODUCTION

SUBSTITUTED ALKYL DIAMINE DERIVATIVES AND YOUR USE AS TACHYKININ AN ANTAGONIST

ASPARTYL PROTEASE INHIBITORS

SUSTIUIERTE CYCLI CONNECTIONS, PROCEDURE FOR YOUR PRODUCTION AS WELL AS IT ABSTENTION PHARMACEUTICAL ZUSAMMESETZUNGEN

POLYAMINE DERIVATIVES, MANUFACTURING PROCESSES FOR IT AND USE OF IT

RETROVIRUSPROTEASE INHIBITORS

SUBSTITUTED HETERO-CYCLIC CONNECTIONS, PROCEDURES FOR YOUR PRODUCTION AND THESE CONNECTIONS ABSTENTION PHARMACEUTICAL COMPOSITIONS

PROCEDURES FOR THE PRODUCTION OF ORGANIC DIURETHANEN AND/OR PU AND YOUR USE DI FOR THE PRODUCTION OF AND/OR POLYISOCYANATEN

PRODUCTION of a SUBSTITUTED ONE 2,5-DIAMINO-3 HYDROXYHEXAN

NEW AMIDE DERIVATIVES AND MEDICAL COMPOSITIONS THIS CONTAINING

POTTING PROCEDURE FOR THE PRODUCTION OF 2 - OXAZOLIDINONDERIVATE

INTERMEDIATE PRODUCTS FOR THE PRODUCTION OF RETROVIRALER PROTEASEHEMMENDEN CONNECTIONS

POLYMERE ONE ON THE BASIS OF BLOCK COPOLYMERS

AMPHIPHILE POLYAMINE CONNECTIONS

CHEMICAL CONSTRUCTIONS

AROMATIC AMINE-SUBSTITUTED LIGANDS WITH VERB-MOVED STICKSTOFF-UND SULFUR DONOR ATOMS FOR PICTURE FIGURATION

PROCEDURE FOR THE PRODUCTION OF RETROVIAL PROTEASE RESTRAINING INTERMEDIATE PRODUCTS

Phenalene-1-one-containing photosensitizer composition, phenalene-1-one compound and the use thereof

The present invention relates to a phenalene-1-one compound, a photosensitizer composition comprising said phenalene-1-one compound, an article comprising said phenalene-1-one compound and/or photosensitizer composition and the use thereof.

AMINOALKYLAMINOCARBONYL AMINODIOL AMINO ACID DERIVATIVES AS ANTI-HYPERTENSIVE AGENTS

8-SUBSTITUTED 2-AMINOTETRALINS

NOVEL PEPTIDASE INHIBITORS

3-(N-METHYL-N-ALKYL)-AMINO 2-METHOXYMETHYLENE PROPAN 1-OL DERIVATIVES, A PREPARATION PROCESS OF THE SAME AND THERAPEUTICAL COMPOSITIONS CONTAINING THEM

Acid labile cationic amphiphiles

RETROVIRAL PROTEASE INHIBITING COMPOUNDS

Sphingoid polyalkylamine conjugates for vaccination

Type 1, 4-naphtoquinone compounds, compositions comprising them and use of these compounds as anti-cancer agents

IMIDAZOLIDINONE COMPOUNDS

Polymeric vehicles which include a phenolic urethane reactivediluent

BIFUNCTIONAL CHELATING AGENTS

RETROVIRAL PROTEASE INHIBITING COMPOUNDS

Hexadentate ligands useful in radiographic imaging agents

1,4-Bis-amino-2-hydroxy-butane derivatives

Polymers based on block copolymers

Urethane and urea fluorosurfactants

The present invention comprises a compound of a compound of Formula 1 wherein R f is a C 2 to C 12 perfluoroalkyl optionally interrupted by one to four moieties each independently selected from the group consisting of —CH 2 —, —O—, —S—, —S(O)—, and —S(O) 2 —; n is 1 to 6; m is 0 to 2, provided that m is less than or equal to n. X and Y are each independently O or NR, R is hydrogen or C 1 to C 6 alkyl; R 1 , and R 2 are each independently C 1 to C 6 alkyl, optionally containing one or more oxygen atoms and may form a ring selected from the group of piperidine, pyrrolidine, and morpholine; and R 3 is O − , (CH 2 ) p C(O)O − , (CH 2 ) p CH(OH)(CH 2 )SO 3 − , and (CH 2 ) q SO 3 − ; p is 1 to 4; and q is 2 to 4 which is useful as a surfactant.

In Vivo Polynucleotide Delivery Conjugates Having Enzyme Sensitive Linkages

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

NOVEL CATIONIC LIPIDS AND METHODS OF USE THEREOF

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 , ...

Compounds for the Treatment/Prevention of Ocular Inflammatory Diseases

The present invention relates to the use of the compounds of formula (I) and their pharmaceutically acceptable salts for the treatment or the prevention of ocular inflammatory diseases, in particular for the treatment and/or prevention of uveitis, severe conjunctivitis, dry eye syndrome or diabetic retinopathy. 125.-. (canceled)27. The method according to claim 26 , wherein the compound of formula (I) is N-[4-[(3-aminopropyl)amino]butyl]-carbamic acid claim 26 , 2-[[6-[(aminoiminomethyl)amino]-hexyl]amino]-2-oxoethyl ester or a pharmaceutically acceptable salt thereof.28. The method according to claim 27 , wherein the compound of formula (I) is N-[4-[(3-aminopropyl)amino]butyl]-carbamic acid claim 27 , 2-[[6-[(aminoiminomethyl)amino]-hexyl]amino]-2-oxoethyl ester claim 27 , tri-hydrochloride.29. The method according to claim 26 , wherein the compound of formula (I) is N-[4-[(3-aminobutyl)amino]butyl]-carbamic acid claim 26 , 2-[[6-[(aminoiminomethyl)-amino]hexyl]amino]-2-oxoethyl ester or a pharmaceutically acceptable salt thereof.30. The method according to claim 29 , wherein the compound of formula (I) is N-[4-[(3-aminobutyl)amino]butyl]-carbamic acid claim 29 , 2-[[6-[(aminoiminomethyl)-amino]hexyl]amino]-2-oxoethyl ester claim 29 , tetra-hydrochloride.31. The method according to claim 26 , wherein the ocular inflammatory disease is non-infectious uveitis claim 26 , severe conjunctivitis claim 26 , dry eye syndrome or diabetic retinopathy.32. The method according to claim 31 , wherein the ocular inflammatory disease is dry eye syndrome.33. The method according to claim 31 , wherein the severe conjunctivitis is vernal keratoconjunctivitis.34. The method according to claim 26 , wherein the compound of formula (I) or pharmaceutically acceptable salt thereof claim 26 , is administered as eye drops.35. The method according to claim 26 , wherein the compound of formula (I) or pharmaceutically acceptable salt thereof claim 26 , is administered as an injectable or an ...

In Vivo Polynucleotide Delivery Conjugates Having Enzyme Sensitive Linkages

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate. 1. A compound for reversibly modifying an amphipathic membrane active polyamine comprising:{'br': None, 'sup': 1', '2, 'R-AA-amidobenzyl-carbonate,'} R comprises steric stabilizer,', {'sup': '1', 'Ais a hydrophobic amino acid, and'}, {'sup': 2', '1, 'Ais a hydrophilic uncharged amino acid linked to Avia an amide bond.'}], 'wherein'}2. The compound of wherein the amidobenzyl is a p-amidobenzyl group.3. The compound of wherein the carbonate is an activated amine reactive carbonate.4. The compound of where R is neutral.5. The compound of wherein R is uncharged.6. The compound of wherein the steric stabilizer is a polyethylene glycol (PEG).7. The compound of wherein Ais selected from the group consisting of: alanine claim 1 , phenylalanine claim 1 , valine claim 1 , leucine claim 1 , isoleucine claim 1 , and tryptophan.8. The compound of wherein Ais selected from the group consisting of: citrulline claim 1 , glycine claim 1 , threonine claim 1 , dimethyllysine claim 1 , asparagine claim 1 , glutamine.10. A delivery polymer for delivering a polynucleotide to a cell in vivo comprising:{'br': None, 'sup': 1', '2, 'sub': y', 'z, 'M—P-M'} P is an amphipathic membrane active polyamine,', {'sup': '1', 'Mcomprises a targeting ligand linked to P via a dipeptide-amidobenzyl-carbamate linkage,'}, {'sup': '2', 'Mcomprises a steric stabilizer linked to P via a dipeptide-amidobenzyl-carbamate linkage ...

EFFICIENT PEPTIDE COUPLINGS AND THEIR USE IN THE SYNTHESIS AND ISOLATION OF A CYCLOPENTA (G) QUINAZOLINE TRISODIUM SALT

A new method for the synthesis of L-Glutamyl-γ-D-Glutamic acid and its use in the synthesis of (2R)-((4S)-carboxy-4-(4,N-(((6S)-2-(hydroxymethyl)-4-oxo-3,4,7,8-tetrahydro-3H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino)benzamido)butanamido)pentanedioic acid, 1 are provided. Also provided is an efficient method for the isolation and purification of the trisodium salt of the abovementioned acid, 2, in a form suitable for long term storage and use in a parenteral dosing form. 1. A method for the synthesis of a L-Glu-γ-D-Glu dipeptide comprising the steps of:a) activating the γ-carboxylic acid of an N-αO-diprotected L-Glu derivative;b) silylating D-glutamic acid; andc) reacting the activated carboxylic acid derivative produced in step a) with the silylated product of step b) to give a protected L-Glu-γ-D-Glu species.2. A method according to claim 1 , wherein in step a) claim 1 , activation comprises conversion of the N-αO-diprotected L-Glu derivative into an activated derivative.3. A method according to claim 2 , wherein activation comprises treatment of the N-αO-diprotected L-Glu derivative with an alkyl chloroformate and a tertiary amine base.4. A method according to claim 3 , wherein the chloroformate is isobutyl chloroformate.5. A method according to whereby the N-αO-diprotected L-Glu derivative is added slowly to a low temperature solution of the alkyl chloroformate and tertiary amine base.6. A method according to claim 5 , wherein the solution of the alkyl chloroformate and tertiary amine base is at a temperature of from −10° C. to −50° C.7. A method according to claim 3 , wherein the tertiary amine base is N-methylmorpholine.8. A method according to wherein the N-αO-diprotected L-Glu derivative is N-benzyloxycarbonyl-L-glutamic acid-α-benzyl ester.9. A method according to wherein in step b) claim 1 , silylation comprises treatment of D-glutamic acid with a silylating agent.10. A method according to claim 9 , wherein the silylating agent is O claim 9 ,N-bis ...

METHODS OF USING CYCLOALKYLMETHYLAMINE DERIVATIVES

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. 2. The method of claim 1 , wherein X is O.3. The method of claim 1 , wherein X is NH.4. The method of claim 1 , wherein Z is O.5. The method of claim 1 , wherein Z is NH.6. The method of claim 1 , wherein Z is a direct bond.7. The method of claim 1 , wherein Ris hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , or isobutyl.8. The method of claim 1 , wherein Ris hydrogen claim 1 , Calkyl claim 1 , or Calkoxy.9. The method of claim 1 , wherein Ris Calkyl.13. The method of claim 12 , wherein Z is O claim 12 , Ris i-butyl claim 12 , Ris H claim 12 , and Ris Calkyl.16. The method of claim 15 , wherein Ris ethyl.18. The method of claim 1 , wherein the carbon denoted with the * is in the R configuration.19. The method of claim 1 , which treats obesity. This application is a divisional application of U.S. application Ser. No. 13/175,824, filed Jul. 1, 2011; which claims priority to Provisional Application No. 61/361,108, filed Jul. 2, 2010. The above-identified applications are incorporated herein by reference in their entireties.The present invention relates to cycloalkylmethylamine derivatives, synthesis of cycloalkylmethylamine derivatives and methods of using cycloalkylmethylamine derivatives for the pharmacological treatment of obesity and obesity related co-morbid indications.Obesity is a chronic disease that affects millions of people across the world especially in the developed countries. It is defined by ...

ORGANOGOLD COMPLEXES AND METHODS FOR MAKING THE SAME

The present invention relates to chiral ligands deriving from α- and β-amino acids, and from metal complexes formed from the same. The ligands are useful with catalytic gold complexes, particularly Au(I) complexes. 12. A compound as defined in any preceding claim , wherein the Au is Au(I).13. A compound as defined in any preceding claim wherein A denotes SOor C(═O).14. A compound as defined in any preceding claim wherein R denotes C-C-alkyl , C-C-fluoroalkyl; or phenyl optionally substituted with 1 to 5 R15. A compound as defined in any preceding claim wherein A-R denotes SOCH , SOC-C-perfluoroalkyl , SOCHMe , SOCHNOor COCHBr.16. A compound as defined in any preceding claim wherein A-R denotes SOCH , SOCF , SOCHMe , SOCHNOor COCHBr.17. A compound as defined in any preceding claim wherein L denotes P(R) , S(R)or N(R).18. A compound as defined in any preceding claim wherein L denotes P(R).19. A compound as defined in any preceding claim wherein L denotes P(R); and Rdenotes CH , CH; or phenyl optionally substituted with 1 to 5 R.20. A compound as defined in any preceding claim wherein L denotes P(R); and Rdenotes phenyl optionally substituted with 1 to 5 R.21. A compound as defined in any preceding claim wherein Rdenotes C-C-alkyl.22. A compound as defined in any preceding claim wherein Rdenotes methyl.23. A compound as defined in any preceding claim wherein Rdenotes C-C-alkyl.24. A compound as defined in any preceding claim wherein Rdenotes methyl25. A compound as defined in any preceding claim wherein Rdenotes H or C-C-alkyl26. A compound as defined in any preceding claim wherein v denotes 1; and t denotes an integer from 2 to 4.27. A compound as defined in any preceding claim wherein v denotes 1; and t denotes 2.2825. A compound as defined in any of - wherein v denotes 0.29. A compound as defined in any preceding claim wherein u denotes 0.3028. A compound as defined in any of - wherein u denotes 1.31. A compound as defined in any preceding claim wherein Rdenotes ...

CYCLOALKYLMETHYLAMINES

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. 2. The method of claim 1 , wherein X is O.3. The method of claim 1 , wherein X is NH.4. The method of claim 1 , wherein Z is O.5. The method of claim 1 , wherein Z is NH.6. The method of claim 1 , wherein Ris halogen.7. The method of claim 1 , wherein Ris alkoxy.8. The method of claim 1 , wherein Ris alkyl.9. The compound of claim 8 , wherein Ris ethyl claim 8 , n-propyl claim 8 , iso-propyl claim 8 , n-butyl claim 8 , s-butyl claim 8 , or t-butyl.10. The compound of claim 1 , wherein Ris hydrogen.11. The method of claim 1 , wherein Ris alkyl.12. The method of claim 1 , wherein Ris aryl.13. The compound of claim 1 , wherein the carbon denoted with the * is in the R configuration.14. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 1 , excipient claim 1 , or diluent. This application is a continuation application of U.S. application Ser. No. 13/175,824, filed Jul. 1, 2011; which claims priority to Provisional Application No. 61/361,108, filed Jul. 2, 2010. This application is also a continuation-in-part of U.S. application Ser. No. 13/866,905, filed Apr. 19, 2013; which is a continuation application of U.S. application Ser. No. 13/176,526, filed Jul. 5, 2011, now U.S. Pat. No. 8,445,714; which is a divisional application of U.S. application Ser. No. 11/856,670, filed Sep. 17, 2007, now U.S. Pat. No. 7,989,500; which claims the benefit of U.S. Provisional Application No. 60/825,868, filed Sep. 15, 2006. The ...

NOVEL INCLUSION COMPOUND

An object of the present invention is to provide a novel curing agent or a curing accelerator for epoxy resin. The curing agent or a curing accelerator for epoxy resin of the present invention is a clathrate compound comprising the following (a1) and (a2):

RENEWABLE POLYMERS AND RESINS AND METHODS OF MAKING THE SAME

The present disclosure relates to methods for producing polymers and resins, the method including a first reacting of at least a first diamine with a first carbonate-containing compound and a second carbonate-containing compound to produce at least one of the polymer or the resin, where the first reacting is according to 3. The composition of claim 2 , wherein R claim 2 , R′ claim 2 , and R″ each comprises at least one of a saturated hydrocarbon chain or an unsaturated hydrocarbon chain having between 1 and 100 carbon atoms.4. The composition of claim 3 , wherein R further comprises at least one of a hydroxyl group claim 3 , an amine group claim 3 , an aryl group claim 3 , an aromatic ring structure claim 3 , a carboxyl group claim 3 , ketone claim 3 , or a sulfur-containing group.7. The composition of claim 6 , wherein at least one of R claim 6 , R claim 6 , R claim 6 , and Rhas between 1 and 100 carbon atoms.8. The composition of claim 7 , wherein at least one of R claim 7 , R claim 7 , R claim 7 , and Rfurther comprises at least one of a branched chain or a straight chain.9. The composition of claim 6 , wherein R further comprises at least one of a hydroxyl group claim 6 , a carboxylic acid group claim 6 , an amine group claim 6 , a benzene ring claim 6 , a phenol group claim 6 , an amide group claim 6 , an indol group claim 6 , an imidazole group claim 6 , a sulfhydryl group claim 6 , or a guanidinium group.11. The composition of claim 10 , wherein R* further comprises at least one of a hydroxyl group claim 10 , a carboxylic acid group claim 10 , an amine group claim 10 , a benzene ring claim 10 , a phenol group claim 10 , an amide group claim 10 , an indol group claim 10 , an imidazole group claim 10 , a sulfhydryl group claim 10 , or a guanidinium group.15. The composition of claim 14 , wherein Rand Rhave a combined total number of carbons between 14 and 18.16. The composition of claim 15 , wherein the combined total number of carbons of Rand Rinclude between ...

COMPOSITIONS FOR IN SITU LABELING OF BACTERIAL CELL WALLS WITH FLUOROPHORES AND METHODS OF USE THEREOF

Disclosed herein are compositions for assessing peptidoglycan biosynthesis in bacteria, for identifying bacteria, and for screening for bacterial cell wall-acting and/or cell wall-disrupting agents via modified D-amino acids and methods of use thereof. Also disclosed are live bacteria having one or more modified D-amino acids as described herein incorporated into peptidoglycan of a bacterial cell wall. 1. An isolated , modified amino acid comprising a D-amino acid covalently attached to a fluorescent label.2. The isolated claim 1 , modified amino acid of claim 1 , wherein the isolated claim 1 , modified amino acid is selected from the group consisting of CyADA claim 1 , AFADA claim 1 , AFADA claim 1 , BADA claim 1 , FADA claim 1 , HADA claim 1 , NADA claim 1 , TADA claim 1 , YADA claim 1 , FDL claim 1 , HDL claim 1 , NDL claim 1 , TDL claim 1 , EDA claim 1 , or ETDA.3. The isolated claim 1 , modified amino acid of claim 1 , wherein the D-amino acid is selected from the group consisting of 3-amino-D-Ala claim 1 , D-Ala claim 1 , D-Asp claim 1 , D-Cys claim 1 , D-Glu and D-Lys.4. A muramylpentapeptide precursor unit comprising an N-acetyl muramic acid (NAM) moiety having a stem peptide of three to five amino acids claim 1 , wherein one or more of the amino acids in the stem peptide comprises a modified amino acid of and optionally an additional modified amino acid claim 1 , wherein the additional modified amino acid comprises a clickable D-amino acid.5. A peptidoglycan unit comprising the muramylpentapeptide precursor unit of covalently linked to an N-acetyl glucosamine (NAG) moiety.6. A live bacterial organism comprising a bacterium having a modified cell wall comprising modified peptidoglycan containing at least one modified amino acid according to claim 1 , and optionally at least one additional modified amino acid claim 1 , wherein the at least one additional amino acid comprises a clickable D-amino acid.7. A method of assessing bacterial cell wall synthesis in ...

NOVEL PROCESS FOR THE PREPARATION OF 1,3-THIAZOL-5-YLMETHYL [(2R,5R)-5- CARBAMOYL) AMINO] -4-(MORPHOLIN-4-YL)BUTANOYL]AMINO}-1,6-DIPHENYLHEXAN-2-YL]CARBAMATE

The present invention relates to novel processes for the preparation 1,3-Thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)-2-[(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl} carbamoyl)amino]-4-(morpholin-4-yl)butanoyl]amino}-1,6-diphenylhexan-2-yl] carbamate having the following structural formula-1 and it's intermediates thereof. 2. The process according to claim 1 , wherein in step-a) a suitable halogenating agent is preferably sodium bromide in combination with trimethylsilyl chloride; the suitable solvent is the mixture of alcohol and dichloromethane;in step-c) the suitable base is selected from inorganic bases, preferably alkali metal carbonates, alkali metal bicarbonates, alkali metal hydroxides;in step-d) the suitable coupling agent is selected form DCC, CDI, DIC, EDC.HCl, and the like; optionally in combination with HOAt, HOBt, HOCt, TBTU, DMAP optionally in presence of a base;in step-e) the suitable deprotecting agent is selected from a strong acid; preferably inorganic acid; most preferably hydrochloric acid;in step-h) the suitable base is selected from inorganic base, organic base; preferably organic base; most preferably diisopropyl ethylamine; the suitable antioxidant is selected from thiols, ascorbic acid; preferably L-ascorbic acid.5. A process according to claim 4 , the suitable amino protecting agent is selected from di-tert.butyl dicarbonate (DIBOC) claim 4 , benzyl chloroformate claim 4 , fluorenylmethyloxy carbonyl chloride (FMOC chloride) claim 4 , acetyl chloride claim 4 , acetic anhydride claim 4 , benzoyl halides claim 4 , benzyl halides claim 4 , tosyl halides claim 4 , tosyl anhydrides claim 4 , alkyl trifluoroacetates such as methyl trifluoroacetate claim 4 , ethyl trifluoroacetate claim 4 , isopropyl trifluoroacetate claim 4 , vinyl trifluoroacetate claim 4 , trifluoroacetic acid claim 4 , trifluoroacetyl chloride and the like; preferably DIBOC; the suitable base is selected from inorganic bases claim 4 , organic bases; preferably organic base; most ...

DENTAL POLYMERIZABLE MONOMERS, COMPOSITIONS, ADHESIVE DENTAL MATERIALS AND KITS

A dental adhesive curable composition containing a polymerizable monomer including a polymerizable monomer represented by formula (1′) and defined amounts of an acidic group-containing polymerizable monomer, a polymerization initiator containing a peroxide and a photopolymerization initiator, and a reductant containing a sulfinic acid compound and/or a salt thereof, and a filler: 2. The dental adhesive curable composition according to wherein the content of the acidic group-containing polymerizable monomer (BC) is 1 to 10 parts by weight based on the total weight of the polymerizable monomer (III)3. A dental adhesive curable kit (αc) for preparing a dental adhesive curable composition (c) described in claim 1 , the dental adhesive curable kit (αc) comprising at least a first composition and a second composition claim 1 ,at least one of the first composition and the second composition including a polymerizable monomer (A),the first composition including a reductant (Dc),the second composition including an acidic group-containing polymerizable monomer (Bc) and a polymerization initiator (Cc).5. The dental adhesive curable composition (C) according to claim 4 , wherein the moiety of the general formula (2c) is the structure represented by the general formula (RB).7. A mobile tooth fixing material (βd) according to claim 6 ,wherein a cured product that is obtained by the following method and that is subjected to a three-point bending test exhibits a breaking energy of not less than 65 mJ,the cured product being obtained by packing the dental adhesive composition (d) into a 2×2×25 mm mold, which is brought into press contact with a polypropylene film and a glass plate, irradiating nine points on each of front and back sides with light for 10 seconds, and polishing a surface of the cured product with #320 waterproof abrasive paper,the three-point bending test being performed such that the obtained cured product is soaked in water at 37° C. overnight, and thereafter is ...

LSD1-SELECTIVE INHIBITOR HAVING LYSINE STRUCTURE

Provided is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: 4. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is any one of the following compounds:2-(N-benzenecarbonyl)amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-(N-tert-butoxycarbonyl)amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[N-(4-methylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[N-(4-tert-butylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[N-(4-chlorobenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[N-(4-fluorobenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[N-(4-trifluoromethylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-{3-[(2-amino)ethylcarbamoyl]benzenecarbonylamino}-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[3-(piperazine-1-carbonyl)benzenecarbonylamino}-6-(trans-2-phenylcyclopropan-1-amino)-N-benzylhexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-(4-methylbenzyl)hexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-(4-fluorobenzyl)hexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-(4-phenylbenzyl)hexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-(4-tert-butylbenzyl)hexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-(3-methylbenzyl)hexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-(3-fluorobenzyl)hexanamide;2-[N-(4-phenylbenzenecarbonyl)]amino-6-(trans-2-phenylcyclopropan-1-amino)-N-(3- ...

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

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 125-. (canceled)27. A lipid particle comprising a lipid of .28. The lipid particle of claim 27 , wherein the particle further comprises a neutral lipid and a lipid capable of reducing aggregation.29. The lipid particle of claim 27 , wherein the lipid particle consists essentially of{'claim-ref': {'@idref': 'CLM-00026', 'claim 26'}, 'a. a lipid of ;'}b. a neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM;c. a sterol; andd. PEG-DMG or PEG-DMA,{'b': 26', '5', '25, 'in a molar ratio of about 20-60% lipid of claim :-% neutral lipid:25-55% stero1:0.5-15% PEG-DMG or PEG-DMA.'}30. The lipid particle of claim 27 , further comprising a therapeutic agent.31. The lipid particle of claim 30 , wherein the therapeutic agent is a nucleic acid.32. The lipid particle of claim 31 , wherein the nucleic acid is a plasmid.33. The lipid particle of claim 31 , wherein the nucleic acid is an immunostimulatory oligonucleotide.34. The lipid particle of claim 31 , wherein the nucleic acid is selected from the group consisting of an siRNA claim 31 , an antisense oligonucleotide claim 31 , a microRNA claim 31 , an antagomir claim 31 , an aptamer claim 31 , and a ribozyme.35. The lipid particle of claim 30 , wherein the therapeutic agent is siRNA.36. The lipid particle of claim 30 , wherein the therapeutic agent is mRNA.37. The lipid particle of claim 29 , wherein the sterol is cholesterol.38. A pharmaceutical composition comprising a lipid particle of and a pharmaceutically acceptable excipient claim 27 , carrier claim 27 , or diluent.38. A pharmaceutical composition comprising a lipid particle of and a pharmaceutically acceptable excipient claim 30 , carrier claim 30 , or diluent. This application is a Continuation application of U.S. application Ser. No. 14/629,991, ...

XYLYLENE DICARBAMATE, METHOD FOR PRODUCING XYLYLENE DIISOCYANATE, XYLYLENE DIISOCYANATE, AND METHOD FOR RESERVING XYLYLENE DICARBAMATE

Xylylene dicarbamate contains impurities represented by formulas (1) to (4) below at a ratio of less than 100 ppm as a total amount thereof on a mass basis. 5. A method for reserving xylylene dicarbamate according to claim 4 , whereina total oxygen amount of an oxygen amount contained in a space portion when xylylene dicarbamate fills a vessel and an oxygen amount dissolved in the xylylene dicarbamate relative to the xylylene dicarbamate is less than 100 ppm. The present invention relates to xylylene dicarbamate, a method for producing xylylene diisocyanate using the xylylene dicarbamate, xylylene diisocyanate obtained by the method for producing xylylene diisocyanate, and a method for reserving xylylene dicarbamate capable of reducing an impurity content.Conventionally, carbamates (urethane compound) such as xylylene dicarbamate have been a useful organic compound as an industrial material having a wide range of applications such as a material of medicine, agricultural chemicals, and the like; a material of various fine chemicals; and furthermore, an analysis agent of alcohols.Recently, such carbamates have been variously considered as a production material of an isocyanate without using phosgene.That is, the isocyanate is an organic compound having an isocyanate group and is widely used as a material of polyurethane. The isocyanate is industrially produced by reaction between amine and phosgene (phosgene method).However, phosgene is highly toxic, strongly corrosive, and disadvantageous in handling. Thus, as a method for producing an isocyanate instead of the phosgene method, a method for producing an isocyanate by thermally decomposing a urethane compound (carbamate) has been recently considered.To be specific, for example, a method in which a formamide compound and dimethyl carbonate are allowed to react in the coexistence of methanol to extract the produced methyl formate to the outside of the system by distillation, while the obtained urethane compound is ...

Carbonated Estolides And Methods Of Making And Using The Same

Disclosed herein are the conversion of estolide compounds having unsaturated fatty acid groups into estolides containing cyclic carbonate moieties and methods of making and using the same. The estolides containing a cyclic carbonate may be used to produce urethane containing estolides. 3. The method according to claim 2 , wherein residual epoxide or unsaturated groups are not present. This application claims the benefit of U.S. Provisional Application No. 62/204,628, filed 13 Aug. 2015, which is incorporated herein by reference in its entirety.Disclosed herein are the conversion of estolide compounds having unsaturated fatty acid groups into estolides containing carbonate moieties and methods of making and using the same.The production of lubricating oils from natural products has been an area of significant study over the past couple of decades and steady incorporation of those products into the lubricant market has been made due to their good lubricity and biodegradability (Biermann, U., Angew. Chem. Int. Ed. Engl., 50: 3854-3871 (2011); Biresaw, G., et al., J. Am. Oil Chem. Soc., 80: 697-704 (2003); Wagner, H., et al., Appl. Catal., A, 221: 429-442 (2001)). Although biobased lubricants are an attractive replacement to petroleum lubricants, these natural materials suffer from performance issues due to poor cold temperature attributes, and poor oxidative and hydrolytic stabilities. To overcome these issues, vegetable oils can be chemically modified by introducing branching or reducing unsaturation in the molecule. An especially effective approach has been the development of a class of compounds known as estolides (Cermak, S., and T. Isbell, T., J. Am. Oil Chem. Soc., 78: 557-565 (2001a)). Estolides are biobased oligomeric esters obtained by the addition of a fatty acid to a hydroxyl containing vegetable oil or fat or by the condensation of a fatty acid across the olefin functionality of a vegetable oil or fat. The newly formed secondary ester groups not only makes ...

HYDROXYURETHANE (METH)ACRYLATE PREPOLYMERS FOR USE IN 3D PRINTING

The present invention relates to prepolymers of formula (I), a process for the production of the prepolymers, photocurable compositions, comprising the prepolymers of formula (I) and their use in a photopolymerization 3D printing process. In contrast to usual urethane (meth)acrylates. The prepolymers of formula (I) can be prepared without using toxic isocyanates and exhibit pending hydroxyl groups along their molecule backbone which allow for the introduction of further side chains or side groups to improve, for example, the interaction with inorganic fillers.

PROCESS FOR PRODUCING (S)-EQUOL

The present application relates to an improved process for the preparation of (S)-equol (1). The present application also relates to novel intermediates of formula (7), (7A), (8) and (9) and their use for the synthesis of (5)-equol. 2. The process of claim 1 , wherein the acid anhydride of step (a) is acetic anhydride.3. The process of claim 1 , wherein the base of step (a) is diisopropylethylamine.4. The process of claim 1 , wherein the base of step (b) is lithium hydroxide.5. The process of claim 1 , wherein hydrogenation of step (c) is preformed in presence of a heterogeneous catalyst.6. The process of claim 5 , wherein the heterogeneous catalyst is palladium on charcoal.7. The process of claim 1 , wherein the base of step (d) is potassium hydroxide.8. The process of claim 1 , wherein the chiral amine of step (e) is selected from a group of N-tert-butylbenzylamine claim 1 , N-benzylmethylamine claim 1 , α-methylbenzylamine claim 1 , α-ethyl-benzylamine claim 1 , 2-amino-3-methylbutane claim 1 , N-octyl-D-glucamine claim 1 , L-prolinol claim 1 , cinchonidine claim 1 , cinchonine claim 1 , N-boc-3-amino piperidine and 3-amino piperidine.9. The process of claim 1 , wherein the reducing agent of step (f) is borane and dimethyl sulfide complex (BH-DMS).12. (canceled)15. (canceled) The present application relates to an improved process for the production of (S)-equol (1). The present application also relates to substantially pure (S)-equol (1).(S)-Equol (1) is chemically known as 4″,7-isoflavandiol. It is produced in the human intestine by bacterial metabolism of daidzein (2). However, only about 30-50% of human population has daidzein to equol converting bacteria. (S)-Equol (1) binds to estrogen receptor-β and is believed to be useful in the prevention of prostate cancer. (S)-Equol (1) is also believed to be responsible for maintaining bone health and physiological changes during menopause.Takashima et al. (Tetrahedron Letters, 2008, 49, 5156-5158) discloses a process ...

Synthesis of dabigatran

The present invention relates to a process for preparation of Dabigatran etexilate or pharmaceutically acceptable salt thereof. The present invention relates to novel compounds, in particular Ethyl-3-{[(2-formyl-1-methyl-1H-benzimidazole-5-yl)carobonyl]-(2-pyridinyl)amino}propanoate and Ethyl-3-{[(2-dichloromethyl-1-methyl-1H-benzimidazole-5-yl)carbonyl]-(2-pyridinyl)amino} propanoate and process for preparation thereof. The present invention further relates to the use of these novel compounds in the preparation of Dabigatran etexilate or pharmaceutically acceptable salt thereof.

PEPTIDE NUCLEIC ACID (PNA) MONOMERS WITH AN ORTHOGONALLY PROTECTED ESTER MOIETY AND NOVEL INTERMEDIATES AND METHODS RELATED THERETO

The present disclosure pertains to peptide nucleic acid (PNA) monomers and oligomers, as well as methods and compositions useful for the preparation of PNA monomer precursors (e.g. PNA Monomer Esters, Backbone Esters and Backbone Ester Acid Salts, as described below) that can be used to prepare PNA monomers wherein said PNA monomers can be used to prepare said PNA oligomers. In some embodiments, the disclosure features sulfonic acid salts of Backbone Ester compounds, which sulfonic acid salts generally tend to be crystalline and can be obtained in reasonably good yield, often without requiring any chromatographic purification of the reaction product of the Backbone Ester synthesis reaction. This disclosure also pertains to novel methods for the synthesis of said Backbone Ester compounds and novel methods for the formation of the related sulfonic acid salts. Exemplary ester groups include, but are not limited to, 2,2,2-trichloroethy-(TCE), 2,2,2-tribromoethyl-(TBE), 2-iodoethyl-groups (2-IE) and 2-bromoethyl-(2-BrE) as the ester group. These particular ester groups can be removed under conditions where both Boc and Fmoc protected amine groups are stable. 23-. (canceled)4. The compound of claim 1 , wherein Y is selected from benzenesulfonate claim 1 , p-toluenesulfonate claim 1 , naphthalenesulfonate claim 1 , p-xylene-2-sulfonate claim 1 , 2 claim 1 ,4 claim 1 ,5-trichlorobenzenesulfonate claim 1 , 2 claim 1 ,6-dimethylbenzenesulfonate claim 1 , 2-mesitylenesulfonate claim 1 , 2-mesitylenesulfonate dihydrate claim 1 , 2-methylbenzene sulfonate claim 1 , 2-ethylbenzenesulfonate claim 1 , 2-isopropylbenzenesulfonate claim 1 , 2 claim 1 ,3-dimethylbenzenesulfonate claim 1 , 2 claim 1 ,4 claim 1 ,6-trimethylbenzenesulfonate claim 1 , and 2 claim 1 ,4 claim 1 ,6-triisopropylbenzenesulfonate.5. The compound of claim 1 , wherein Y is p-toluenesulfonate.67-. (canceled)8. The compound of claim 1 , wherein Ris H or D.911-. (canceled)12. The compound of claim 1 , wherein Pgis ...

CONFORMATIONALLY-PREORGANIZED, MiniPEG-CONTAINING GAMMA-PEPTIDE NUCLEIC ACIDS

The present invention relates to γ-PNA monomers according to Formula I where substituent groups R1, R2, R3, R4, R5, R6, B and P are defined as set forth in the specification. The invention also provides methodology for synthesizing compounds according to Formula I and methodology for synthesizing PNA oligomers that incorporate one or more Formula I monomers.

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

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: 2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. The cationic lipid of claim 1 , wherein X and Y are O.10. (canceled)11. The cationic lipid of claim 1 , wherein Ais —CH—.12. (canceled)13. (canceled)14. The cationic lipid of claim 1 , wherein Z′ is N(Q).15. (canceled)16. (canceled)17. The cationic lipid of claim 1 , wherein Z′ is alkyl.18. The cationic lipid of claim 1 , wherein Ris alkylamine.19. (canceled)20. (canceled)21. The cationic lipid of claim 1 , wherein Q is alkyl.22. (canceled)23. (canceled)24. (canceled)26. (canceled)27. (canceled)28. (canceled)29. (canceled)30. (canceled)31. (canceled)32. (canceled)33. (canceled)34. (canceled)35. (canceled)36. (canceled)37. (canceled)38. (canceled)39. (canceled)41. (canceled)42. (canceled)43. A lipid particle comprising a compound of .44. (canceled)45. A lipid particle comprising a compound of .46. The lipid particle of claim 43 , wherein the particle further comprises a therapeutic agent.47. The lipid particle of claim 45 , wherein the particle further comprises a therapeutic agent.48. (canceled)49. The lipid particle of claim 46 , wherein the therapeutic agent is a nucleic acid.50. The lipid particle of claim 47 , wherein the therapeutic agent is a nucleic acid.51. (canceled)52. The lipid particle of claim 49 , wherein the nucleic acid is siRNA or mRNA.53. The lipid particle of claim 50 , wherein the nucleic acid is siRNA or mRNA.54. (canceled)55. A method of treating a disease or disorder in a subject in need thereof claim 46 , comprising administering to the subject the lipid particle of .56. A method of treating a disease or disorder in a subject in need thereof claim 47 , comprising administering to the subject the lipid particle of . This application ...

PREPARATION OF NOVEL FLUOROCOMPOUNDS, METHODS OF PREPARATION AND COMPOSITIONS MADE THEREFROM

Novel fluorinated compounds, their method of preparation and use are disclosed, as well as the incorporation of new and old fluorinated compounds in controlled radical polymerization processes to efficiently produce polymer compositions with unique and enhanced properties. Various cure mechanisms and types of end-uses are disclosed. 2. (canceled)3. (canceled)5. (canceled)6. A method of forming a fluorinated moisture curing silane comprising:i) mixing an organo silane compound and an alkali or alkaline earth metal oxide in a reaction vessel under heat; andii) further combining the resultant mixture with a fluorinated alkanol and permitting the reaction to proceed to form a moisture curing fluorinated silane.7. (canceled)8. An adhesive , sealant or coating composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(i) one or more compounds of .'}9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. An adhesive , sealant or coating composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(i) one or more compounds of ;'}(ii) one or more reactive components selected from the group consisting of monomers, polymers, oligomers, reactive diluents and combinations thereof; and(iii) a cure system.17. The compound of being moisture curable.18. The compound of wherein the compound of structure I includes at least one alkoxy group. This invention relates to novel fluorocompounds, their preparation and use, as well as compositions which employ such fluoro compounds. Additionally, this invention relates to the controlled polymerization of compositions containing fluoro compounds, including methods for living radical polymerization of monomers and oligomers with, inter alfa, increased conversion, high polydispersity and high functionality.Fluorinated polymers are known to be useful in many industrial applications due to their unique characteristics, such as high thermo-stability, chemical inertness and ...

Polyamine Transporter Selective Compounds as Anti-Cancer Agents

Several aromatic hydrocarbons di-substituted with a polyamine are described according to formulas selected from compounds 4, 7, 10, 15 and pharmaceutically acceptable salts thereof. The novel dimeric polyamines of the present invention demonstrate enhanced penetration into cells having an upregulated polyamine transport system, such as various types of cancer cells. The disclosed aromatic polyamine dimers provide highly efficient drugs for targeting cancer cells with active polyamine transporters. 2. A pharmaceutical composition comprising the aromatic hydrocarbon of or a pharmaceutically acceptable salt thereof; anda pharmaceutically acceptable carrier.3. A method of treating a leukemia or melanoma cancer cell claim 1 , the method comprising contacting the cell with a compound claim 1 , conjugate or pharmaceutically acceptable salt thereof claim 1 , wherein the compound is the aromatic hydrocarbon compound of claim 1 , or a pharmaceutically acceptable salt thereof.5. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'the hydrocarbon compound of or a pharmaceutically acceptable salt thereof; and'}a pharmaceutically acceptable carrier.7. A pharmaceutical composition comprising the aromatic hydrocarbon of or a pharmaceutically acceptable salt thereof; anda pharmaceutically acceptable carrier.8. A method of treating a leukemia or melanoma cancer cell claim 6 , the method comprising contacting the cell with a compound claim 6 , conjugate or pharmaceutically acceptable salt thereof claim 6 , wherein the compound is the aromatic hydrocarbon compound of claim 6 , or a pharmaceutically acceptable salt thereof. This application is a divisional of U.S. Ser. No. 13/953,667 filed Jul. 29, 2013 which is a divisional of U.S. Ser. No. 12/113,540 filed May 1, 2008 and further claims priority to provisional application Ser. No. 60/915,448 filed on May 2, 2007, all of which are incorporated herein by reference in their entirety.The present ...

(meth)acrylate-functionalized waxes and curable compositions made therewith

The present invention relates to (meth)acrylate-functionalized waxes and curable compositions, such as anaerobic adhesive compositions, made therewith.

METHOD FOR PRODUCING CARBAMATE COMPOUND, CARBAMATE COMPOUND, AND METHOD FOR PRODUCING ISOCYANATE COMPOUND USING SAME

The present invention relates to a method of producing a carbamate compound, comprising reacting a fluorine-containing carbonic diester compound represented by formula (1) and a non-aromatic diamine compound represented by formula (2) without using a catalyst, to thereby produce a carbamate compound represented by formula (3), and a method of producing an isocyanate compound represented by formula (20) from the carbamate compound without using a catalyst, wherein R represents a fluorine-containing monovalent aliphatic hydrocarbon group, and A represents a divalent aliphatic hydrocarbon group, a divalent alicyclic hydrocarbon group or a divalent aromatic-aliphatic hydrocarbon group. This application is a Divisional of U.S. application Ser. No. 13/630,915, filed Sep. 28, 2012 which is a Continuation application filed under 35 U.S.C. 111(a) claiming the benefit under 35 U.S.C. §§120 and 365(c) of PCT International Application No. PCT/JP2011/056095 filed on Mar. 15, 2011, which is based upon and claims the benefit of priority of Japanese Application No. 2010-086126 filed on Apr. 2, 2010, the entire contents of which are hereby incorporated by reference in their entireties.This invention relates to a method of producing a carbamate compound, a carbamate compound obtained by the method and a method of producing an isocyanate compound using the carbamate compound.Isocyanate compounds are industrially broadly used as materials of, for example, various urethane compounds and urea compounds; and curing agents of resins and paints.For example, the following methods are known as the method of producing isocyanate compounds.(1) A method of reacting a primary amine with phosgene. This is mainly used industrially.(2) A method of thermally decomposing a carbamate compound having —N(H)—C(O)O— in its molecule in the presence of a catalyst (e.g. Patent Reference 1).(3) A method in which a non-aromatic carbamate compound is obtained by reacting a non-aromatic diamine, which does not ...

INHIBITORS OF DEUBIQUITINATING PROTEASES

Disclosed are small molecule inhibitors of deubiquitinating enzymes (DUBs), and methods of using them. Certain compounds display a preference for specific ubiquitin specific proteases (USPs). 23-. (canceled)58-. (canceled)1012-. (canceled)14. (canceled)16. (canceled)17. The compound of claim 1 , wherein the compound is a compound of Formula I or a compound of Formula II; and n is 1.18. The compound of claim 1 , wherein the compound is a compound of Formula I or a compound of Formula II; and m is 1.19. (canceled)20. The compound of claim 1 , wherein the compound is a compound of Formula I or a compound of Formula II; and Ris —H.2127-. (canceled)28. The compound of claim 1 , wherein Ris —C(O)ORor an optionally substituted benzyl.2938-. (canceled)4046-. (canceled)4853-. (canceled)5669-. (canceled) This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/813,328, filed Apr. 18, 2013; the contents of which are hereby incorporated by reference.This invention was made with government support under R01-GM100921 awarded by the National Institutes of Health. The government has certain rights in the invention.The ubiquitin system is the linchpin in maintenance of cellular fitness. While many studies have focused on ubiquitylation pathways, comparatively little is known about deubquitination proteins (DUBs). DUBs are a large group of proteases that regulate ubiquitin-dependent regulatory pathways by cleaving ubiquitin-protein bonds. DUBs can also cleave C-terminally modified ubiquitin. DUBs are also commonly referred to as deubiquinating proteases, deubiquitylating proteases, deubiquitylating proteinases, deubiquinating proteinases, deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitylating isozpeptidases, deubiquitinases, deubiquitylases, ubiquitin proteases, ubiquitin hydrolyases, ubiquitin isopeptidases, or DUbs. The human genome encodes in five gene families nearly 100 DUBs with specificity for ubiquitin. ...

DENTAL COMPOSITES

Disclosed herein are methacrylate compounds that can be used as components of dental composites. Also disclosed are dental composites comprising the compositions and thiourethane oligomers. 2. The compound of wherein X is benzyl.3. The compound of wherein Rand Rare methyl.4. The compound of wherein Y is N and Ris H claim 3 , methyl or ethyl.5. The compound of wherein Y is C and Rand Rare methyl.6. The compound of wherein X is butyl.7. The compound of wherein Y is N and Ris methyl or ethyl.8. The compound of wherein Y is C and Rand Rare both methyl.9. A dental composite composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a resin composition comprising the compound of ,'}a thiourethane oligomer; anda filler composition.10. The dental composite of wherein the thiourethane oligomer is thiol terminated.11. The dental composite of wherein the thiourethane oligomer is isocyanate terminated.12. A method of preparing a dental composite claim 9 , the method comprising:contacting an isocyanate compound selected from 1,6-hexanediol-diisocyanate, 1,3-bis(1-isocyanato-1methylethylbenzene), or bis(4-isocyanotocyclohexyl) methane with a thiol compound selected from methyl-3-mercaptopriopionate, pentaerythritol tetra-3-mercaptopriopionate or trimethylol-tris-3-mercaptopropionate in the presence of triethylamine to make a thiourethane oligomer, wherein the isocyanate compound is added in sufficient excess that the thiourethane oligomer comprises pendant thiols;adding the thiourethane oligomer to the composite;adding a dimethacrylate composition to the composite;adding a tertiary amine, d-camphorquinone, and an inhibitor to the composite;adding a filler composition to the composite,wherein the thiourethane oligomer comprises at least 10% of the composite.13. The method of wherein the dimethacrylate composition comprises the compound of .14. The method of wherein the isocyanate compound is added to the thiol compound in a 2:1 ratio.15. The method of wherein the ...

Method for Preparing Urethane (Meth)Acrylates

Described is a process for preparing urethane (meth)acrylates. In a first step, a hydroxyalkyl (meth)acrylate (A) is reacted with a lactone (B) in the presence of at least one catalyst (C), selected from the group consisting of iron compounds, titanium compounds, aluminum compounds, zirconium compounds, manganese compounds, nickel compounds, zinc compounds, cobalt compounds, and bismuth compounds to provide a product; and, in a further step, the product is reacted with a polyisocyanate (D) which comprises at least one hydroxyalkyl (meth)acrylate bonded via an allophanate group. 2. The urethane (meth)acrylate according to claim 1 , wherein Ris selected from the group consisting of 1 claim 1 ,2-ethylene claim 1 , 1 claim 1 ,2- or 1 claim 1 ,3-propylene claim 1 , 1 claim 1 ,2- claim 1 , 1 claim 1 ,3- claim 1 , or 1 claim 1 ,4-butylene claim 1 , 1 claim 1 ,1-dimethyl-1 claim 1 ,2-ethylene claim 1 , 1 claim 1 ,2-dimethyl-1 claim 1 ,2-ethylene claim 1 , 1 claim 1 ,5-pentylene claim 1 , 1 claim 1 ,6-hexylene claim 1 , 1 claim 1 ,8-octylene claim 1 , 1 claim 1 ,10-decylene claim 1 , and 1 claim 1 ,12-dodecylene.3. The urethane (meth)acrylate according to claim 1 , wherein Ris selected from the group consisting of methylene claim 1 , 1 claim 1 ,2-ethylene claim 1 , 1 claim 1 ,2-propylene claim 1 , 1 claim 1 ,3-propylene claim 1 , 1 claim 1 ,2-butylene claim 1 , 1 claim 1 ,3-butylene claim 1 , 1 claim 1 ,4-butylene claim 1 , 1 claim 1 ,5-pentylene claim 1 , 1 claim 1 ,5-hexylene claim 1 , 1 claim 1 ,6-hexylene claim 1 , 1 claim 1 ,8-octylene claim 1 , 1 claim 1 ,10-decylene claim 1 , 1 claim 1 ,12-dodecylene claim 1 , 2-oxa-1 claim 1 ,4-butylene claim 1 , 3-oxa-1 claim 1 ,5-pentylene claim 1 , or 3-oxa-1 claim 1 ,5-hexylene.4. The urethane (meth)acrylate according to claim 1 , wherein the catalyst is a titanium compound claim 1 , zinc compound claim 1 , or bismuth compound.6. The process according to claim 5 , wherein the polyisocyanate (D) is obtained by reacting at least ...

NOVEL PHOTOCLEAVABLE MASS-TAGS FOR MULTIPLEXED MASS SPECTROMETRIC IMAGING OF TISSUES USING BIOMOLECULAR PROBES

The field of this invention relates to immunohistochemistry (IHC) and in situ hybridization (ISH) for the targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells for example, for research use and for clinical use such by pathologists (e.g., biomarker analyses of a resected tumor or tumor biopsy). In particular, the use of mass spectrometric imaging (MSI) as a mode to detect and map the biomolecules in tissues or cells for example. More specifically, the field of this invention relates to photocleavable mass-tag reagents which are attached to probes such as antibodies and nucleic acids and used to achieve multiplex immunohistochemistry and in situ hybridization, with MSI as the mode of detection/readout. Probe types other than antibodies and nucleic acids are also covered in the field of invention, including but not limited to carbohydrate-binding proteins (e.g., lectins), receptors and ligands. Finally, the field of the invention also encompasses multi-omic MSI procedures, where MSI of photocleavable mass-tag probes is combined with other modes of MSI, such as direct label-free MSI of endogenous biomolecules from the biospecimen (e.g., tissue), whereby said biomolecules can be intact or digested (e.g., chemically digested or by enzyme).

POLYOLS FROM BIOMASS AND POLYMERIC PRODUCTS PRODUCED THEREFROM

Polyol compositions containing methane linkages derived from amino acids. The polyols are obtained from the reaction of the carbonate with the cadres in the amino acids. Individual amino acids or mixtures of amino acids that are prepared from the hydrolysis of the proteins can be used. 1. A process of producing multi-hydroxy polyols , said process comprising:a. providing a biomass material;b. hydrolyzing said biomass material to amino acids;c. condensing said amino acids with a diamine to produce amine terminated monomers;d. reacting said monomers with a carbonate to provide hydroxyl terminated urethane oligomers.2. A process of producing multi-hydroxy polyols as claimed in wherein claim 1 , in addition there is a step e. of alkoxylating any carbohydrates in the biomass to produce hydroxyl groups.3. A product produced by the process of .4. A product produced by the process of .5. A process as claimed in wherein the biomass material is a meal produced by the extraction of oil from vegetable seed.6. A process of producing multi-hydroxy polyols claim 1 , said process comprising:a. providing a material selected from a group consisting essentially of i. proteins, ii. amino acids derived from proteins, and, iii. mixtures of i. and ii.;b. condensing any amino acids in said proteins or amino acids derived from said proteins with a diamine to produce amino terminated monomers;c. reacting said monomers with a carbonate to provide hydroxyl terminated urethane oligomers.7. A product produced by the process of .8. A process of producing multi-hydroxy polyols as claimed in wherein claim 6 , in addition claim 6 , there is a step d. of alkoxylating any carbohydrates in the protein to produce hydroxyl groups.9. A product produced by the process of .10. A process of producing multi-hydroxy polyols claim 8 , the method comprising;a. removing any carbohydrates from a biomass material;b. hydrolyzing said biomass material to amino acids;c. condensing said amino acids with a diamine to ...

Novel photocleavable mass-tags for multiplexed mass spectrometric imaging of tissues using biomolecular probes

The field of this invention relates to immunohistochemistry (IHC) and in situ hybridization (ISH) for the targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells for example, for research use and for clinical use such by pathologists (e.g., biomarker analyses of a resected tumor or tumor biopsy). In particular, the use of mass spectrometric imaging (MSI) as a mode to detect and map the biomolecules in tissues or cells for example. More specifically, the field of this invention relates to photocleavable mass-tag reagents which are attached to probes such as antibodies and nucleic acids and used to achieve multiplex immunohistochemistry and in situ hybridization, with MSI as the mode of detection/readout. Probe types other than antibodies and nucleic acids are also covered in the field of invention, including but not limited to carbohydrate-binding proteins (e.g., lectins), receptors and ligands. Finally, the field of the invention also encompasses multi-omic MSI procedures, where MSI of photocleavable mass-tag probes is combined with other modes of MSI, such as direct label-free MSI of endogenous biomolecules from the biospecimen (e.g., tissue), whereby said biomolecules can be intact or digested (e.g., chemically digested or by enzyme).

LINEAR GLYCIDYL CARBAMATE (GC) RESINS FOR HIGHLY FLEXIBLE COATINGS

This invention relates to coating compositions comprising a linear glycidyl carbamate (GC) resin and a curing agent. The linear GC-resins were synthesized using linear and cycloaliphatic diisocyanates and a combination of diols and optional triols with glycidol. The combination of linear diisocyanates and diols introduces a more linear structure in the GC-resin compositions. 1. A linear isocyanate terminated urethane compound , comprising the reaction product of at least one diisocyanate , at least one diol and , optionally , at least one triol , {'br': None, 'O═C═N—R—N═C═O'}, 'wherein the diisocyanate has the following structure{'sub': 2', '18', '2', '18', '2', '18, 'wherein R is a divalent hydrocarbyl group selected from a straight or branched C-Calkylene group, C-Calkenylene group, and C-Calkynylene group, and a divalent cyclic group;'} {'br': None, 'HO—R′—OH'}, 'wherein the diol has the following structurewherein R′ is selected from a divalent hydrocarbyl group and a divalent ether group; and{'sub': 3', '10, 'wherein the optional triol is selected from a C-Calkyl triol.'}2. The compound of claim 1 , wherein R is selected from a C-Calkyl and a C-Ccycloalkyl.4. The compound of claim 1 , wherein the diisocyanate compound is selected from hexamethylene diisocyanate claim 1 , trimethyl hexamethylene diisocyanate claim 1 , dicyclohexyl diisocyanate claim 1 , isophorone diisocyanate claim 1 , 4 claim 1 ,4′-methylene diphenyl diisocyanate claim 1 , 2 claim 1 ,2′-methylene diphenyl diisocyanate claim 1 , 2 claim 1 ,4′-methylene diphenyl diisocyanate claim 1 , 1 claim 1 ,3-phenylene diisocyanate claim 1 , 1 claim 1 ,4-phenylene diisocyanate claim 1 , 1 claim 1 ,4-cyclohexyl diisocyanate claim 1 , meta-tetramethylxylylene diisocyanate claim 1 , 2 claim 1 ,4-toluene diisocyanate claim 1 , 2 claim 1 ,6-toluene diisocyanate claim 1 , and mixtures thereof.5. The compound of claim 1 , wherein the diol is selected from diethyleneglycol claim 1 , 2-butyl-2-ethyl-1 claim 1 ,3- ...

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

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 125-. (canceled)27. The lipid of claim 26 , wherein Ris ω-aminoalkyl claim 26 , ω-(substituted)aminoalkyl claim 26 , ω-phosphoalkyl claim 26 , or ω-thiophosphoalkyl.28. The lipid of claim 27 , wherein Ris ω-(substituted)aminoalkyl.29. The lipid of claim 26 , wherein Ris 2-(dimethylamino)ethyl claim 26 , 3-(diisopropylamino)propyl claim 26 , or 3-(N-ethyl-n-isopropylamino)-1-methylpropyl.30. The lipid of claim 26 , wherein Ris H claim 26 , optionally substituted C-Calkyl claim 26 , optionally substituted C-Calkenyl claim 26 , or optionally substituted C-Calkynyl.31. The lipid of claim 26 , wherein Ris alkylaminoalkyl claim 26 , dialkylaminoalkyl claim 26 , or alkylheterocycle.32. The lipid of claim 26 , wherein Rand Rare each optionally substituted C-Calkyl or optionally substituted C-Calkenyl.33. The lipid of claim 26 , wherein Rand Rare each linoleyl.34. A lipid particle comprising a lipid of .35. The lipid particle of claim 34 , wherein the particle further comprises a neutral lipid and a lipid capable of reducing aggregation.36. The lipid particle of claim 35 , wherein the lipid capable of reducing aggregation is a PEG-lipid.37. The lipid particle of claim 34 , further comprising a therapeutic agent.38. The lipid particle of claim 37 , wherein the therapeutic agent is a nucleic acid.39. The lipid particle of claim 38 , wherein the nucleic acid is selected from the group consisting of an siRNA and an antisense oligonucleotide.40. The lipid particle of claim 37 , wherein the nucleic acid is siRNA.41. The lipid particle of claim 37 , wherein the nucleic acid is mRNA.42. A pharmaceutical composition comprising a lipid of and a pharmaceutically acceptable excipient claim 26 , carrier claim 26 , or diluent.43. A pharmaceutical composition comprising a lipid particle of and a pharmaceutically ...

CONFORMATIONALLY-PREORGANIZED, MiniPEG-CONTAINING GAMMA-PEPTIDE NUCLEIC ACIDS

The present invention relates to γ-PNA monomers according to Formula I where substituent groups R, R, R, R, R, R, B and P are defined as set forth in the specification. The invention also provides methodology for synthesizing compounds according to Formula I and methodology for synthesizing PNA oligomers that incorporate one or more Formula I monomers. 118-. (canceled)23. The method of claim 22 , wherein steps (c) through (f) are performed at least once using an automated solid-phase synthesizer.24. A PNA oligomer comprising at least one gamma PNA monomer subunit claim 23 , wherein said PNA oligomer is produced by the method of .28. The PNA oligomer of claim 27 , wherein x is an integer from 1 to 4 inclusive claim 27 , and Ris selected from the group consisting of hydrogen (H) and methyl.31. The PNA oligomer of claim 30 , wherein x is an integer from 1 to 4 inclusive and Ris selected from the group consisting of hydrogen (H) and methyl.32. The PNA oligomer of claim 25 , wherein X is selected from the group consisting of adenine claim 25 , cytosine claim 25 , guanine claim 25 , thymine and uracil.33. The PNA oligomer of claim 25 , wherein said PNA oligomer is support bound.34. The PNA oligomer of claim 25 , wherein said PNA oligomer is dissolved in an aqueous solution.36. The compound of claim 35 , whereinZ is selected from the group consisting of iodine and hydroxyl;{'sub': 1', '2', '2', '2', 'x', '8', '2, 'Ris —CH—[O(CH)]—ORand Ris H, wherein x is an integer from 1 to 4 inclusive;'}{'sub': '5', 'Ris selected from the group consisting of hydrogen (H) and methyl; and'}{'sub': '8', 'Ris selected from the group consisting of hydrogen, methyl, ethyl, and t-butyl.'}37. The compound of claim 35 , whereinZ is selected from the group consisting of iodine and hydroxyl;{'sub': 2', '2', '2', '2', 'x', '8', '1, 'Ris —CH—[O(CH)]—ORand Ris H, wherein x is an integer from 1 to 4 inclusive;'}{'sub': '5', 'Ris selected from the group consisting of hydrogen (H) and methyl; and'}{'sub ...

COMPOUND HAVING POLYMERIZABLE GROUP AND CROSSLINKABLE GROUP AND METHOD FOR PRODUCING THE SAME

An acrylic or methacrylic compound having N-alkoxyalkyl group; and a method for producing the compound. An acrylic or methacrylic compound having N-alkoxyalkyl group, of Formula [1]: 2. The compound according to claim 1 , wherein{'sup': '2', 'sub': 2-10', '5-6', '5-6, 'Ris a Calkylene group, a divalent group consisting of a Caliphatic ring, or a divalent aliphatic group containing a Caliphatic ring, the group optionally containing an ether bond in its structure and the alkylene group being optionally linear or branched;'}{'sup': '3', 'sub': 2-10', '5-6', '5-6', '2-20, 'Ris an r-valent Caliphatic group, an r-valent group consisting of a Caliphatic ring, or an r-valent aliphatic group containing a Caliphatic ring, the group optionally containing an ether bond in its structure and the r-valent Caliphatic group being optionally linear or branched;'}{'sup': '4', 'sub': '1-6', 'Ris a linear or branched Calkyl group; and'}r is 2 to 6.3. The compound according to claim 1 , wherein Ris methyl group claim 1 , ethyl group claim 1 , n-propyl group claim 1 , or n-butyl group.4. The compound according to claim 1 , wherein Ris ethylene group.5. The compound according to claim 1 , wherein Ris n-hexylene group and r is 2.7. The method according to claim 6 , wherein{'sup': '2', 'sub': 2-10', '5-6', '5-6, 'Ris a Calkylene group, a divalent group consisting of a Caliphatic ring, or a divalent aliphatic group containing a Caliphatic ring, the group optionally containing an ether bond in its structure and the alkylene group being optionally linear or branched;'}{'sup': '3', 'sub': 2-20', '5-6', '5-6', '2-20, 'Ris an r-valent Caliphatic group, an r-valent group consisting of a Caliphatic ring, or an r-valent aliphatic group containing a Caliphatic ring, the group optionally containing an ether bond in its structure and the r-valent Caliphatic group being optionally linear or branched;'}{'sup': '4', 'sub': '1-6', 'Ris a linear or branched Calkyl group; and'}r is 2 to 6.8. The method ...

COMPOSITIONS FOR IN SITU LABELING OF BACTERIAL CELL WALLS WITH FLUOROPHORES AND METHODS OF USE THEREOF

Disclosed herein are compositions for assessing peptidoglycan biosynthesis in bacteria, for identifying bacteria, and for screening for bacterial cell wall-acting and/or cell wall-disrupting agents via modified D-amino acids and methods of use thereof. Also disclosed are live bacteria having one or more modified D-amino acids as described herein incorporated into peptidoglycan of a bacterial cell wall. 1. A modified amino acid comprising a D-amino acid covalently attached to a fluorescent label.2. The modified amino acid of claim 1 , wherein the fluorescent label is 7-hydroxycoumarin 3-carboxylic acid (HCC-OH) claim 1 , 7-nitrobenzofurazan (NBD) claim 1 , 4-chloro-7-nitrobenzofurazan (NBD-Cl) claim 1 , ADA claim 1 , CyADA claim 1 , AFADA claim 1 , AFADA claim 1 , BADA claim 1 , FADA claim 1 , HADA claim 1 , NADA claim 1 , TADA claim 1 , YADA claim 1 , FDL claim 1 , HDL claim 1 , NDL claim 1 , TDL claim 1 , AHA claim 1 , EDA claim 1 , ETDA claim 1 , fluorescein (F) or carboxytetramethylrhodamine (T).3. The modified amino acid of or claim 1 , wherein the D-amino acid is selected from the group consisting of 3-amino-D-Ala claim 1 , D-Ala claim 1 , D-Asp claim 1 , D-Cys claim 1 , D-Glu and D-Lys.4. A muramylpentapeptide precursor unit comprising an N-acetyl muramic acid (NAM) moiety having a stem peptide of three to five amino acids claim 1 , wherein one or more of the amino acids in the stem peptide comprises a modified amino acid of any one of the preceding claims and optionally an additional modified amino acid claim 1 , wherein the additional modified amino acid comprises a clickable D-amino acid.5. A peptidoglycan unit comprising the muramylpentapeptide precursor unit of covalently linked to an N-acetyl glucosamine (NAG) moiety.6. A live bacterial organism comprising a bacterium having a modified cell wall comprising modified peptidoglycan containing at least one modified amino acid according to any one of to claim 4 , and optionally at least one additional ...

FUSED CYCLOOCTYNE COMPOUNDS AND THEIR USE IN METAL-FREE CLICK REACTIONS

The invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene. 116-. (canceled)18. The compound according to claim 17 , wherein the compound is of the Formula (IIa).19. The compound according to claim 17 , wherein p is 1 and L is CH.20. The compound according to claim 17 , wherein Q is selected from the group consisting of —OR claim 17 , —N(R) claim 17 , —N(R) claim 17 , —C(O)N(R6) claim 17 , —C(O)OR claim 17 , —OC(O)R claim 17 , —OC(O)OR claim 17 , —OC(O)N(R) claim 17 , —N(R)C(O)R claim 17 , —N(R)C(O)ORand —N(R)C(O)N(R) claim 17 , wherein Ris as defined in .21. The compound according to claim 17 , wherein Q is —OH.22. The compound according to claim 17 , wherein Ris hydrogen.23. The compound according to claim 17 , wherein Ris hydrogen or [(L)-Q].24. The compound according to claim 17 , wherein n is 0.25. The compound according to claim 19 , wherein Q is —OH claim 19 , Ris hydrogen claim 19 , Ris hydrogen or [(L)-Q] and n is 0.26. A conjugate comprising a compound according to conjugated to a label via a functional group Q.27. A conjugate according o claim 26 , wherein functional group Q is connected to the label via a linking unit.281. The conjugate according to claim 26 , wherein functional group Q is connected to the label via a linking unit of the structure Q-S-Q claim 26 , wherein Q is defined as in claim claim 26 , and wherein S is selected from the group consisting of linear or branched C-Calkylene groups claim 26 , C-Calkenylene groups claim ...

3,3-DIPHENYL-N-(1-PHENYLETHYL) PROPAN-1-AMINE: AS A NEW SELECTIVE LIGAND OF THE SIGMA-1 RECEPTORS, WITH ANTI-APOPTOTIC (CYTOPROTECTIVE) PROPERTIES AND PROTOTYPICAL ANTICANCER ACTIVITY

3,3-diphenyl-N-(1-phenylethyl) propan-1-amine (fendiline): as a new selective ligand of the sigma-1 receptors, with anti-apoptotic (cytoprotective) properties and prototypical anticancer activity. This invention concerns the prototypical profile of selective sigma-1 ligand and the putative therapeutical properties of the compound 3,3-diphenyl-N-(1-phenylethyl) propan-1-amine (DPPA) and its pharmaceutically acceptable salts, with cytoprotective activity, more specifically for neurons against the neurodegenerative diseases (e.g. Alzheimer's disease, Huntington's disease, Parkinson's disease) via their anti-apoptotic properties induced by their selective sigma-1 agonism. Concerning the cancer cells, DPPA exhibited pro-apoptotic properties associated with neuroprotective activity originating a prototypical anticancer profile consisting in synergistical association with the clinically used anticancer drugs with its analgesic and neuroprotective activities antagonizing the neuropathic pain induced by the later. 18-. (canceled)9. A compound comprising an effective amount of a compound selected from the group consisting of 3 ,3-diphenyl-N-(1-phenylethyl) propan-1-amine , a pharmaceutically acceptable salt thereof , and combinations thereof , said compound being as prototypical selective ligands of sigma-1 receptors with anti-apoptotic activity on normal cells and pro-apoptotic properties on cancer cells.10. A pharmaceutical composition comprising an effective amount of a compound , and at least one pharmaceutically acceptable excipient , said compound being selected from the group consisting of 3 ,3-diphenyl-N-(1-phenylethyl) propan-1-amine , a pharmaceutically acceptable salt thereof , and combinations thereof , said compound being as prototypical selective ligands of sigma-1 receptors with anti-apoptotic activity on normal cells and pro-apoptotic properties on cancer cells.11. A method of using a compound comprising an effective amount of a compound selected from the ...

METHOD FOR SYNTHESIZING AMINES

The invention relates to a process for preparing certain amines, wherein, in a first step, a corresponding amino alcohol is reacted with a suitable carbonyl compound and then, in a second step, the intermediate obtained in the first step is reacted with a suitable amine component to form the desired amine. 117.-. (canceled)19. The process according to claim 18 , characterized in that claim 18 , in step A claim 18 , the amino alcohol of the formula (2) is used in an amount that is 0.8 to 1.9 times the molar amount based on the molar amount of the carbonyl groups in the carbonyl compound of the formula (3).20. The process according to claim 18 , characterized in that claim 18 , in step B claim 18 , the amine component of the formula (5) is used in an amount that is 1.5 to 10 times the amount based on the molar amount of the alcohol groups in the intermediate of the formula (4).21. The process according to claim 18 , for preparing amines of the formula (1) in which m is 2 claim 18 , where{'sup': '1', 'Ris an optionally substituted phenylene, cyclohexylene, dicycloheptylene, tricyclododecylene, pentacyclopentadecylene, furandiyl, tetrahydrofurandiyl, thiophenediyl, tetrahydrothiophenediyl, or N,N′-piperazine-bis(2,2-dimethylpropane)diyl radical, and'}{'sup': '2', 'sub': '2', 'Ris hydrogen (H), methyl or phenyl.'}23. The process according to for preparing amines of the formula (1) in which m is 1 claim 18 , where{'sup': 1', '2', '1', '2', '1', '2, 'Rand Rare both methyl or both phenyl, Ris 3-methylbutyl and Ris methyl, or Ris n-pentyl and Ris ethyl,'}or{'sup': '1', 'Ris selected from the group consisting of i-propyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,5-dimethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2,3-dimethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2,4,5-trimethylphenyl, 2,4,6-trimethylphenyl, 2,4,5-trimethoxyphenyl, 2,4, ...

Method for producing meta-xylylenediisocyanates

A method for producing meta-xylylenediisocyanates includes a reaction step in which monohalogenated benzenes, formaldehydes, and an amide compound represented by general formula (1) below are allowed to react in the presence of an acidic liquid to produce a bisamide compound; a dehalogenation step in which in the bisamide compound, the halogen atom derived from the monohalogenated benzenes is replaced with a hydrogen atom; and a thermal decomposition step in which the bisamide compound from which the halogen atom is eliminated is subjected to thermal decomposition. In the reaction step, the acidic liquid contains inorganic acid, the equivalent ratio of the hydrogen atom of the inorganic acid relative to the monohalogenated benzenes is more than 14, the acidic liquid has an inorganic acid concentration of more than 90 mass %, and the reaction temperature is more than 10° C. General formula (1): wherein R 1 represents an alkoxy group or an amino group.

PEPTIDE NUCLEIC ACID (PNA) MONOMERS WITH AN ORTHOGONALLY PROTECTED ESTER MOIETY AND NOVEL INTERMEDIATES AND METHODS RELATED THERETO

The present disclosure pertains to peptide nucleic acid (PNA) monomers and oligomers, as well as methods and compositions useful for the preparation of PNA monomer precursors (e.g. PNA Monomer Esters, Backbone Esters and Backbone Ester Acid Salts, as described below) that can be used to prepare PNA monomers wherein said PNA monomers can be used to prepare said PNA oligomers. In some embodiments, the disclosure features sulfonic acid salts of Backbone Ester compounds, which sulfonic acid salts generally tend to be crystalline and can be obtained in reasonably good yield, often without requiring any chromatographic purification of the reaction product of the Backbone Ester synthesis reaction. This disclosure also pertains to novel methods for the synthesis of said Backbone Ester compounds and novel methods for the formation of the related sulfonic acid salts. Exemplary ester groups include, but are not limited to, 2,2,2-trichloroethy-(TCE), 2,2,2-tribromoethyl-(TBE), 2-iodoethyl-groups (2-IE) and 2-bromoethyl-(2-BrE) as the ester group. These particular ester groups can be removed under conditions where both Boc and Fmoc protected amine groups are stable. 2. The compound of claim 1 , wherein the sulfonate anion is produced from a sulfonic acid selected from the group consisting of: benzenesulfonic acid claim 1 , naphthalenesulfonic acid claim 1 , p-xylene-2-sulfonic acid claim 1 , 2 claim 1 ,4 claim 1 ,5-trichlorobenzenesulfonic acid claim 1 , 2 claim 1 ,6-dimethylbenzenesulfonic acid claim 1 , 2-mesitylenesulfonic acid claim 1 , 2-mesitylenesulfonic acid dihydrate claim 1 , 2-methylbenzene sulfonic acid claim 1 , 2-ethylbenzenesulfonic acid claim 1 , 2-isopropylbenzenesulfonic acid claim 1 , 2 claim 1 ,3-dimethylbenzenesulfonic acid claim 1 , 2 claim 1 ,4 claim 1 ,6-trimethylbenzenesulfonic acid and 2 claim 1 ,4 claim 1 ,6-triisopropylbenzenesulfonic acid.3. The compound of claim 1 , wherein the sulfonate anion is produced from p-toluenesulfonic acid.4. The compound ...

NOVEL CATIONIC LIPIDS AND METHODS OF USE THEREOF

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. 23-. (canceled)519-. (canceled)2131-. (canceled)33. A lipid particle comprising a cationic lipid of .34. The lipid particle of claim 33 , wherein the particle further comprises a non-cationic lipid.35. The lipid particle of claim 34 , wherein the non-cationic lipid is selected from the group consisting of a phospholipid claim 34 , cholesterol claim 34 , or a mixture of a phospholipid and cholesterol.3637-. (canceled)38. The lipid particle of claim 33 , wherein the particle further comprises a conjugated lipid that inhibits aggregation of particles.39. The lipid particle of claim 38 , wherein the conjugated lipid that inhibits aggregation of particles comprises a polyethyleneglycol (PEG)-lipid conjugate.40. The lipid particle of claim 39 , wherein the PEG-lipid conjugate comprises a PEG-diacylglycerol (PEG-DAG) conjugate claim 39 , a PEG-dialkyloxypropyl (PEG-DAA) conjugate claim 39 , or a mixture thereof.41. The lipid particle of claim 33 , wherein the particle further comprises a therapeutic agent.42. The lipid particle of claim 41 , wherein the therapeutic agent is a nucleic acid.43. The lipid particle of claim 42 , wherein the nucleic acid is an interfering RNA.44. The lipid particle of claim 41 , wherein the therapeutic agent is mRNA.45. The lipid particle of claim 43 , wherein the interfering RNA is an siRNA.4649-. ...

XYLYLENE DICARBAMATE, METHOD FOR PRODUCING XYLYLENE DIISOCYANATE, XYLYLENE DIISOCYANATE, AND METHOD FOR RESERVING XYLYLENE DICARBAMATE

Xylylene dicarbamate contains impurities represented by formulas () to () below at a ratio of less than ppm as a total amount thereof on a mass basis. 25-. (canceled) The present invention relates to xylylene dicarbamate, a method for producing xylylene diisocyanate using the xylylene dicarbamate, xylylene diisocyanate obtained by the method for producing xylylene diisocyanate, and a method for reserving xylylene dicarbamate capable of reducing an impurity content.Conventionally, carbamates (urethane compound) such as xylylene dicarbamate have been a useful organic compound as an industrial material having a wide range of applications such as a material of medicine, agricultural chemicals, and the like; a material of various fine chemicals; and furthermore, an analysis agent of alcohols.Recently, such carbamates have been variously considered as a production material of an isocyanate without using phosgene.That is, the isocyanate is an organic compound having an isocyanate group and is widely used as a material of polyurethane. The isocyanate is industrially produced by reaction between amine and phosgene (phosgene method).However, phosgene is highly toxic, strongly corrosive, and disadvantageous in handling. Thus, as a method for producing an isocyanate instead of the phosgene method, a method for producing an isocyanate by thermally decomposing a urethane compound (carbamate) has been recently considered.To be specific, for example, a method in which a formamide compound and dimethyl carbonate are allowed to react in the coexistence of methanol to extract the produced methyl formate to the outside of the system by distillation, while the obtained urethane compound is thermally decomposed to obtain an isocyanate compound has been proposed.Patent Document 1 below has, for example, proposed that in a thermal decomposition reactor of such a urethane compound, a storage tank (material tank) of the urethane compound is in a nitrogen atmosphere and that the obtained ...

Methods for Treating or Preventing Fatigue

The present invention relates to the use of compounds of the invention for treatment and/or prevention of fatigue, including fatigue associated with diseases or treatments. 2. The method of claim 1 , wherein R is hydrogen and x=1.3. The method of claim 1 , wherein R claim 1 , R claim 1 , and Rare all hydrogen and x=1.5. The method of claim 1 , wherein the compound of Formula I is an enantiomer substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of the compound predominates.6. The method of claim 5 , wherein one enantiomer predominates to the extent of at least about 90%.7. The method of claim 5 , wherein one enantiomer predominates to the extent of at least about 98%.9. The method of claim 1 , wherein the fatigue is associated with a disease claim 1 , disorder or condition.10. The method of claim 9 , wherein the disease claim 9 , disorder or condition is selected from the group consisting of depression claim 9 , cancer claim 9 , multiple sclerosis claim 9 , Parkinson's disease claim 9 , Alzheimer's disease claim 9 , chronic fatigue syndrome claim 9 , fibromyalgia claim 9 , chronic pain claim 9 , traumatic brain injury claim 9 , AIDS claim 9 , and osteoarthritis.11. The method of claim 1 , wherein the fatigue is associated with a treatment or medication.12. The method of claim 11 , wherein the treatment or medication is selected from the group consisting of chemotherapy claim 11 , radiation therapy claim 11 , bone marrow transplant claim 11 , and anti-depressant treatment.13. The method of claim 1 , wherein the compound is administered concurrently with an additional agent or treatment.14. The method of claim 1 , wherein the compound is administered prior to an event that may result in fatigue claim 1 , concurrently with an event that may result in fatigue claim 1 , and/or after the onset of fatigue.15. The method of claim 1 , wherein the treatment or prevention effective amount of the compound is from about 0.01 mg/kg/dose to ...

METHOD FOR PRODUCING COMPOUND, COMPOUND, EPOXY CURING AGENT, AND METHOD FOR PRODUCING AMINE COMPOSITION

Provided are: a method for producing a compound that excels in storage stability and handleability; the compound; and an epoxy curing agent containing the compound. The method for producing a compound represented by Formula (1-1) includes subjecting the compound represented by Formula (5-1) to an addition reaction to add ethylene and/or propylene in the presence of a base. In Formula (5-1), Rto Reach independently represent a hydrogen atom, an ethyl group, an n-propyl group, or an isopropyl group, and n is an integer of from 1 to 3. In Formula (1-1), Rto Reach independently represent a hydrogen atom, an ethyl group, an n-propyl group, or an isopropyl group, and n is an integer of from 1 to 3. 3. The compound production method according to claim 1 , wherein the base is a base composition comprising:at least one alkali metal-containing compound (A) which is selected from the group consisting of rubidium carbonate, rubidium hydroxide, cesium carbonate, and cesium hydroxide; anda metallic sodium (B).4. The compound production method according to claim 1 , comprising dividing the base into two or more portions and introducing into a reaction system.5. The compound production method according to claim 1 , wherein n in Formula (5-1) is 1.6. The compound production method according to claim 1 , wherein the compound represented by Formula (5-1) and/or the compound represented by Formula (5-2) comprises at least one compound selected from the group consisting of benzylamine claim 1 , α-methyl benzenemethanamine claim 1 , α-ethyl benzenemethanamine claim 1 , o-xylylenediamine claim 1 , m-xylylenediamine claim 1 , p-xylylenediamine claim 1 , 1 claim 1 ,2 claim 1 ,3-benzene trimethanamine claim 1 , 1 claim 1 ,2 claim 1 ,4-benzene trimethanamine and 1 claim 1 ,2 claim 1 ,4 claim 1 ,5-benzene tetramethanamine.7. The compound production method according to claim 1 , wherein the compound represented by Formula (5-1) comprises m-xylylenediamine.9. The compound production method ...

DENTAL POLYMERIZABLE MONOMERS

Provided are dental polymerizable monomers that can give cured products having high toughness and high rigidity, dental polymerizable monomer compositions containing the polymerizable monomers, and dental compositions containing the dental polymerizable monomer compositions, and cured products thereof having high mechanical properties. The dental polymerizable monomer (A) which includes a urethane acrylate obtained from an appropriately rigid diisocyanate and an appropriately flexible hydroxyacrylate is used to prepare a dental polymerizable monomer composition containing the dental polymerizable monomer, and a dental composition containing the dental polymerizable monomer composition. 2. The dental polymerizable monomer (A) according to claim 1 , wherein in the general formula (1) claim 1 , Ris a hydrogen atom.5. The dental polymerizable monomer (A) according to claim 1 , wherein Rand Rin the general formula (1) independently at each occurrence represents a Clinear alkylene group or a Clinear oxyalkylene group claim 1 , each of which is optionally substituted with a Calkyl group in place of a hydrogen atom.6. A dental polymerizable monomer composition comprising the dental polymerizable monomer (A) described in .7. The dental polymerizable monomer composition according to claim 6 , wherein the viscosity at 25° C. is 1 to 100 claim 6 ,000 mPa·s.8. A dental composition comprising the dental polymerizable monomer composition described in claim 6 , a polymerization initiator and a filler.9. A dental material obtained by curing the dental composition described in . The present invention relates to novel dental polymerizable monomers, dental polymerizable monomer compositions including the polymerizable monomers, dental compositions including the dental polymerizable monomer compositions, and cured products obtained by curing the dental compositions.Composite resins that are typical examples of dental compositions usually contain polymerizable monomer compositions ...

Improved process for the preparation of carbamates

A process for the preparation of N-(dialkylaminoalkyl)-carbamic acid esters, in particular (propyl N-[3-(dimethylamino)propyl] carbamate) comprising an oxidative carbonylation reaction of a compound of general structure (II) wherein each of R 1 and R 2 , equal to or different from each other, are independently selected from an alkyl group having 1 to 10 carbon atoms, which is optionally substituted by at least one halogen atom, an aryl group or an aralkyl group; R 3 is selected from an alkyl group having 1 to 36 carbon atoms, which is optionally substituted by at least one halogen atom, an aryl group or an aralkyl group; each of R′, R″ and R 4 , equal to or different from each other, are independently selected from H, an alkyl group having 1 to 10 carbon atoms, which is optionally substituted by at least one halogen atom, an aryl group or an aralkyl group; and n is an integer in the range from 1 to 8, with a hydroxyl compound of general formula (III), R 3 —OH (III) and in the presence of a catalyst system.

COMPOSITIONS FOR IN SITU LABELING OF BACTERIAL CELL WALLS WITH FLUOROPHORES AND METHODS OF USE THEREOF

Disclosed herein are compositions for assessing peptidoglycan biosynthesis in bacteria, for identifying bacteria, and for screening for bacterial cell wall-acting and/or cell wall-disrupting agents via modified D-amino acids and methods of use thereof. Also disclosed are live bacteria having one or more modified D-amino acids as described herein incorporated into peptidoglycan of a bacterial cell wall. 1. A modified amino acid comprising a D-amino acid covalently attached to a fluorescent label.2. The modified amino acid of claim 1 , wherein the fluorescent label is 7-hydroxycoumarin 3-carboxylic acid (HCC—OH) claim 1 , 7-nitrobenzofurazan (NBD) claim 1 , 4-chloro-7-nitrobenzofurazan (NBD-Cl) claim 1 , ADA claim 1 , CyADA claim 1 , AFADA claim 1 , AFADA claim 1 , BADA claim 1 , FADA claim 1 , HADA claim 1 , NADA claim 1 , TADA claim 1 , YADA claim 1 , FDL claim 1 , HDL claim 1 , NDL claim 1 , TDL claim 1 , AHA claim 1 , EDA claim 1 , ETDA claim 1 , fluorescein (F) or carboxytetramethylrhodamine (T).3. The modified amino acid of claim 1 , wherein the D-amino acid is selected from the group consisting of 3-amino-D-Ala claim 1 , D-Ala claim 1 , D-Asp claim 1 , D-Cys claim 1 , D-Glu and D-Lys.4. A muramylpentapeptide precursor unit comprising an N-acetyl muramic acid (NAM) moiety having a stem peptide of three to five amino acids claim 1 , wherein one or more of the amino acids in the stem peptide comprises a modified amino acid of any one of the preceding claims and optionally an additional modified amino acid claim 1 , wherein the additional modified amino acid comprises a clickable D-amino acid.5. A peptidoglycan unit comprising the muramylpentapeptide precursor unit of covalently linked to an N-acetyl glucosamine (NAG) moiety.6. A live bacterial organism comprising a bacterium having a modified cell wall comprising modified peptidoglycan containing at least one modified amino acid according to claim 1 , and optionally at least one additional modified amino acid ...

CONFORMATIONALLY-PREORGANIZED, MiniPEG-CONTAINING GAMMA-PEPTIDE NUCLEIC ACIDS

The present invention relates to γ-PNA monomers according to Formula I where substituent groups R, R, R, R, R, R, B and P are defined as set forth in the specification. The invention also provides methodology for synthesizing compounds according to Formula I and methodology for synthesizing PNA oligomers that incorporate one or more Formula I monomers. 2. The compound according to claim 1 , wherein each of Rand Ris independently —CH—O—(CH—CH—O)P.3. The compound according to claim 2 , wherein Ris —CH—(O—CH—CH—)OPand Ris selected from the group consisting of H and linear or branched (C-C)alkyl.4. The compound according to claim 3 , wherein Ris —CH—(O—CH—CH—)OPand Ris H.5. The compound according to claim 4 , wherein Pis H or (C-C)alkyl.6. The compound according to claim 1 , having stereochemical purity in the range from about 80% to about 99% at the Cγ-position.7. The compound according to claim 6 , having stereochemical purity of at least 90% at the Cγ-position.8. The compound according to claim 6 , having stereochemical purity of at least 99% at the Cγ-position.916-. (canceled)18. The method of claim 17 , wherein steps (a) through (f) are performed using an automated solid-phase synthesizer.19. The compound of claim 1 , wherein B is adenine.20. The compound of claim 1 , wherein B is guanine.21. The compound of claim 1 , wherein B is cytosine.22. The compound of claim 1 , wherein B is thymine.23. The compound of claim 1 , wherein B is uracil. This application is a continuation of U.S. patent application Ser. No. 16/362,579, filed on Mar. 22, 2019, which is continuation of U.S. patent application Ser. No. 16/145,075, filed Sep. 27, 2018, (now U.S. Pat. No. 10,364,272) which is a divisional of U.S. patent application Ser. No. 14/921,755, filed Oct. 23, 2015 (now U.S. Pat. No. 10,093,700), which is a continuation of U.S. patent application Ser. No. 14/110,689, filed Jan. 17, 2014 (now U.S. Pat. No. 9,193,758), which is a U.S. national stage of PCT/US2012/032459, filed ...

NOVEL TRIALKYL CATIONIC LIPIDS AND METHODS OF USE THEREOF

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. 26-. (canceled)7. The cationic lipid of claim 1 , wherein R claim 1 , R claim 1 , and Rindependently comprise at least one site of unsaturation.8. The cationic lipid of claim 7 , wherein R claim 7 , R claim 7 , and Rare independently selected from the group consisting of a dodecenyl moiety claim 7 , a tetradecenyl moiety claim 7 , a hexadecenyl moiety claim 7 , an octadecenyl moiety claim 7 , and an icosadecenyl moiety.911-. (canceled)12. The cationic lipid of claim 1 , wherein R claim 1 , R claim 1 , and Rindependently comprise at least two sites of unsaturation.13. The cationic lipid of claim 12 , wherein R claim 12 , R claim 12 , and Rare independently selected from the group consisting of a dodecadienyl moiety claim 12 , a tetradecadienyl moiety claim 12 , a hexadecadienyl moiety claim 12 , an octadecadienyl moiety claim 12 , and an icosadienyl moiety.1416-. (canceled)17. The cationic lipid of claim 1 , wherein R claim 1 , R claim 1 , and Rindependently comprise at least three sites of unsaturation.18. The cationic lipid of claim 17 , wherein R claim 17 , R claim 17 , and Rare independently selected from the group consisting of a dodecatrienyl moiety claim 17 , a tetradectrienyl moiety claim 17 , a hexadecatrienyl moiety claim 17 , an octadecatrienyl moiety claim 17 , and an icosatrienyl moiety.1921-. (canceled)22. ...

COPOLYMERS OF ISOCYANATOALKYLTRIALKOXYSILANES AND URETHANEDIOLS

The present invention relates to a copolymer of the formula 2. The copolymer according to claim 1 , wherein each A is independently a linear C-Calkylene radical.3. The copolymer according to claim 1 , wherein each R is independently a methyl claim 1 , ethyl or isopropyl radical.4. The copolymer according to claim 1 , wherein each B is independently a linear claim 1 , branched or cyclic C-Calkylene radical.5. The copolymer according to claim 1 , wherein each D is independently a (cyclo)aliphatic C-Calkylene radical.7. A process for preparing the copolymer according to claim 1 , the process comprising:reacting at least one diol with at least one diisocyanate to give a urethane intermediate, andsubsequently reacting the urethane intermediate with at least one isocyanatoalkyltrialkoxysilane.8. A coating composition or a constituent of a coating composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the copolymer according to .'}9. A coating composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'A) at least one copolymer according to ,'}B) a binder component,C) optionally up to 4 wt % of a catalyst,D) optionally an auxiliary and an additive, andE) optionally an organic solvent.10. The coating composition according to claim 9 , wherein component B) is selected from the group consisting of a hydroxyl-comprising polyester claim 9 , a polyether claim 9 , a poly(meth)acrylate claim 9 , a polycarbonate and a polyurethane having an OH number of from 20 to 500 mg KOH/g and an average molar mass of from 250 to 6000 g/mol.11. The coating composition according to claim 9 , wherein component C) is at least one catalyst selected from the group consisting of: C1) an organic carboxylic acid having a melting point above 60° C. and C2) a tetraalkylammonium carboxylate.12. The coating composition according to claim 11 , wherein component C2) is at least one selected from the group consisting of tetramethylammonium formate claim 11 ...

AMINE FOR LOW-EMISSION EPOXY RESIN COMPOSITIONS

An amine of the formula (I) and a process for its preparation by reductive alkylation of 1,2-propylenediamine with a di- or trifunctional carbonyl compound and hydrogen. The amine of the formula (I) is low in viscosity and in odour, high in reactivity towards epoxides and outstanding in its compatibility with other amines and with epoxy resins. The amine of the formula (I) allows access to low-emission epoxy resin compositions which have good processing qualities, cure rapidly even at low temperatures and form high-quality, high-hardness plastics having an attractive surface. 2. The amine of the formula (I) as claimed in claim 1 , wherein n is 2.3. The amine of the formula (I) as claimed in claim 1 , wherein R is a hydrogen radical.4. The amine of the formula (I) as claimed in claim 1 , wherein A is an optionally substituted phenylene or cyclohexylene or dicycloheptylene or tricyclodecylene or pentacyclopentadecylene or furandiyl or tetrahydrofurandiyl or thiophenediyl or tetrahydrothiophenediyl or N claim 1 ,N′-piperazine-bis(2 claim 1 ,2-dimethylpropane)diyl radical.5. The amine of the formula (I) as claimed in claim 1 , wherein it is 1 claim 1 ,4-bis(2-aminopropylaminomethyl)benzene or 1 claim 1 ,4-bis(2-aminopropylaminomethyl)cyclohexane.7. The process as claimed in claim 6 , wherein 1 claim 6 ,2-propylenediamine is used in stoichiometric excess over the carbonyl groups of the carbonyl compound of the formula (III).8. A method claim 1 , comprising: hardening epoxy resins with an amine of the formula (I) as claimed in .9. A hardener for epoxy resins claim 1 , comprising at least one amine of the formula (I) as claimed in and at least one further amine and/or at least one accelerator.10. The hardener as claimed in claim 9 , wherein the accelerator is salicylic acid or 2 claim 9 ,4 claim 9 ,6-tris(dimethylaminomethyl)phenol or a combination thereof.11. The hardener as claimed in claim 9 , wherein the further amine comprises 1-(2-aminopropylaminomethyl)-4-(1- ...

SURFACE ACTIVE IONIC LIQUID WITH ACTIVITY IN AQUEOUS AND NON-AQUEOUS MEDIA

Disclosed herein are surfactant compounds, that are surface active, liquid, chiral, and micelle forming. Also disclose herein are ionic liquids and compsitions comprising the surfactant compounds. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of claim 2 , wherein Ris hydrogen.4. The compound of claim 3 , wherein Ris Calkyl.5. The compound of claim 4 , wherein Ris CH.6. The compound of claim 3 , wherein n is 0.7. The compound of claim 3 , wherein Ris —C(O)Calkyl.8. The compound of claim 7 , wherein Ris —C(O)CH.9. The compound of claim 7 , wherein Ris —C(O)Calkyl.10. The compound of claim 9 , wherein Ris —C(O)CH.11. The compound of claim 3 , wherein Ris Calkyl.12. The compound of claim 11 , wherein Ris straight chain Calkyl.16. An ionic liquid comprising a plurality of compounds of .17. A composition comprising the compound of .18. The composition of further comprising an aqueous medium claim 17 , wherein the compound has a critical micelle concentration of about 0.0001-0.0005 M in the aqueous medium.19. The composition of further comprising a micellar aggregate claim 17 , the micellar aggregate comprising a plurality of compounds of any of -.20. The composition of claim 19 , wherein the micellar aggregate comprises a spherical micelle claim 19 , a rod-like micelle claim 19 , and/or a lamellar structure.21. The composition of further comprising an organic medium claim 17 , wherein the compound has a critical micelle concentration of about 0.003-0.1 M in the organic medium.22. The composition of further comprising a reverse micellar aggregate claim 17 , the reverse micellar aggregate comprising a plurality of the compound of any of -. This application claims priority to U.S. Provisional Application No. 62/621,216, filed Jan. 24, 2018, which is hereby incorporated by reference in its entirety.This invention was made with government support under grant number CHE1464874 awarded by the National Science Foundation. The government has certain rights in ...

Isocyanate Production Process Using Composition Containing Carbamic Acid Ester and Aromatic Hydroxy Compound, and Composition for Transfer and Storage of Carbamic Acid Ester

An object of the present invention is to provide an isocyanate production process, which is free of the various problems found in the prior art, and which uses a composition containing a carbamic acid ester and an aromatic hydroxy compound when producing isocyanate without using phosgene, as well as a carbamic acid ester composition for transferring or storing carbamic acid ester. The present invention discloses an isocyanate production process including specific steps and using a composition containing a carbamic acid ester and an aromatic hydroxy compound, as well as a composition for transfer or storage of carbamic acid ester comprising the carbamic acid ester and the specific aromatic hydroxy compound. 144-. (canceled) The present invention relates to a process for producing an isocyanate using a composition containing a carbamic acid ester and an aromatic hydroxy compound. Moreover, the present invention relates to a composition for transfer and storage of carbamic acid ester, containing such a composition.Carbamic acid esters (urethanes) are compounds that are widely used in applications such as polyurethane foam, surface coatings, elastomers, paints and adhesives, and are industrially extremely useful. In addition, carbamic acid esters are also useful as raw materials for producing isocyanates without using phosgene.Industrial production of isocyanates mainly uses a reaction between an amine compound and phosgene (“phosgene method”), and nearly the entire amount of isocyanates produced worldwide is produced using the phosgene method. However, the phosgene method has numerous problems.Firstly, a large amount of phosgene is used as a raw material. Phosgene is an extremely highly toxic substance, its handling requires special precautions to prevent handlers from being exposed, and special measures are also required to detoxify waste.Secondly, since a large amount of highly corrosive hydrogen chloride is produced as a by-product of the phosgene method, in ...

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

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 125-. (canceled)28. A lipid particle comprising a lipid of .29. A lipid particle comprising a lipid of .30. The lipid particle of claim 28 , wherein the particle further comprises a neutral lipid and a lipid capable of reducing aggregation.32. The lipid particle of claim 28 , further comprising a therapeutic agent.33. The lipid particle of claim 32 , wherein the therapeutic agent is a nucleic acid.34. The lipid particle of claim 33 , wherein the nucleic acid is a plasmid.35. The lipid particle of claim 33 , wherein the nucleic acid is an immunostimulatory oligonucleotide.36. The lipid particle of claim 33 , wherein the nucleic acid is selected from the group consisting of an siRNA claim 33 , an antisense oligonucleotide claim 33 , a microRNA claim 33 , an antagomir claim 33 , an aptamer claim 33 , and a ribozyme.37. The lipid particle of claim 36 , wherein the nucleic acid is an siRNA.38. The lipid particle of claim 36 , wherein the molar ratio is 52% lipid of : 5% neutral lipid: 30% sterol: 13% PEG-DMG.39. A pharmaceutical composition comprising a lipid particle of and a pharmaceutically acceptable excipient claim 28 , carrier claim 28 , or diluent.40. A method of modulating the expression of a target gene in a cell claim 32 , comprising providing to a cell the lipid particle of .41. The method of claim 40 , wherein the therapeutic agent is selected from an siRNA claim 40 , an antagomir claim 40 , an antisense oligonucleotide claim 40 , and a plasmid capable of expressing an siRNA claim 40 , a ribozyme claim 40 , an aptamer or an antisense oligonucleotide.42. The method of claim 40 , wherein the target gene is selected from the group consisting of Factor VII claim 40 , Eg5 claim 40 , PCSK9 claim 40 , TPX2 claim 40 , apoB claim 40 , SAA claim 40 , TTR ...

NOVEL DIAMINE, POLYAMIC ACID, AND POLYIMIDE

To provide a novel diamine, and a polyimide precursor and a polyimide using it. A diamine represented by the formula (1): 2: The diamine of claim 1 , wherein in the formula (1) claim 1 , each of Xand Xis independently a single bond or —CH—.3: The diamine of claim 1 , wherein in the formula (1) claim 1 , each of Xand Xis independently —CH—.4: The diamine of claim 1 , wherein in the formula (1) claim 1 , each of Yand Yis independently a single bond or —O—.5: The diamine of claim 1 , wherein in the formula (1) claim 1 , Yand Yare symmetrical.6: The diamine of claim 1 , wherein in the formula (1) claim 1 , a is 0.7: The diamine of claim 1 , wherein in the formula (1) claim 1 , R is a t-butyl group or a 9-fluorenylmethyl group.8: The diamine of claim 1 , wherein in the formula (1) claim 1 , each of Yand Yis a single bond.11: The polyimide precursor claim 10 , wherein the diamine component comprises the diamine in an amount of from 20 to 100 mol %.12: A polyimide obtained by imidizing the polyimide precursor as defined in . The present invention relates to a novel diamine to be a material of a polyimide having an aliphatic secondary amino group in its main chain, and a polyamic acid and a polyimide using it.As a polymer produced by using a diamine as a monomer, a condensation polymer such as a polyamide, a polyamic acid, a polyimide, a polyamic acid ester, a polyamide imide or a polyetherimide has been known. Such a condensation polymer has been used as various electronic materials, and it may be used for a wide range of applications, for example, for a liquid crystal alignment film, an optical film, an adhesive film for a semiconductor, an interlayer dielectric film, etc.It has been known that an excellent liquid crystal alignment film can be obtained from a functional polymer having amino groups introduced to a main chain or side chains of such a condensation polymer. When using such a liquid crystal alignment film, scars on the film surface and peeling of the film ...

Ethoxylate isocyanate compound and its use as a emulsifier

Provided is a composition comprising one or more compound having the structure of formula II: wherein A is a residue of a polyisocyanate, L is a linking group formed by a reaction of an isocyanate group with an isocyanate-reactive group, n is 5 to 25, m is 0 to 100, and Z is methyl or ethyl or propyl, and wherein the ratio of the sum of the moles of isocyanate groups plus the moles of said L groups to the moles of said Z groups is 2:1 to 30:1. Also provided is an emulsion in which the particles comprise such a composition and further comprise one or more water-insoluble compound that does not have the structure A-NCO,

CURING AGENT FOR WATER-BASED EPOXY RESIN, WATER-BASED EPOXY RESIN COMPOSITION, AND CURED PRODUCT THEREOF

A curing agent for a water-based epoxy resin, including a reaction composition (A) containing a reaction product of styrene and an amine compound represented by the following formula (1), a water-based epoxy resin composition containing the same, and a cured product thereof. 1. A curing agent for a water-based epoxy resin , comprising a reaction composition (A) comprising a reaction product of styrene and an amine compound represented by the following formula (1):{'br': None, 'sub': 2', '2', '2', '2, 'HN—CH-A-CH—NH\u2003\u2003(1)'}wherein A is a 1,2-phenylene group, a 1,3-phenylene group, or a 1,4-phenylene group.3. The curing agent according to claim 1 , wherein A is a 1 claim 1 ,3-phenylene group.4. The curing agent according to claim 1 , wherein a content of the reaction composition (A) in the curing agent is 30% by mass or more.5. The curing agent according to claim 1 , further comprising a reaction composition comprising a reaction product of a compound having at least one epoxy group in a molecule thereof and a polyamine compound.6. The curing agent according to claim 5 , wherein the reaction composition is a reaction composition (B) comprising a reaction product of epichlorohydrin and the amine compound represented by the formula (1).8. The curing agent according to claim 5 , wherein the reaction composition is a reaction composition (C) comprising a reaction product of a compound having at least two epoxy groups in a molecule thereof and a polyamine compound.9. A water-based epoxy resin composition comprising the curing agent according to and a water-based epoxy resin.10. The water-based epoxy resin composition according to claim 9 , wherein the water-based epoxy resin is an epoxy resin emulsion comprising an epoxy resin claim 9 , an emulsifier claim 9 , and water.11. The water-based epoxy resin composition according to claim 10 , wherein an HLB of the emulsifier defined by a Griffin method is from 8.0 to 20.0.12. The water-based epoxy resin composition ...

METHODS FOR TREATING OR PREVENTING FATIGUE

The present invention relates to the use of compounds of the invention for treatment and/or prevention of fatigue, including fatigue associated with diseases or treatments. 115-. (canceled)17. The method of claim 16 , wherein the compound of Formula I is the hydrochloride salt.18. The method of claim 16 , wherein R is hydrogen and x=1.19. The method of claim 16 , wherein R claim 16 , R claim 16 , and Rare all hydrogen and x=1.21. The method of claim 16 , wherein the compound of Formula I is an enantiomer substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of the compound predominates.22. The method of claim 21 , wherein one enantiomer predominates to the extent of at least about 90%.23. The method of claim 21 , wherein one enantiomer predominates to the extent of at least about 98%.25. The method of claim 16 , wherein the compound is administered concurrently with an additional agent or treatment.26. The method of claim 16 , wherein the treatment or prevention effective amount of the compound is from about 0.01 mg/kg/dose to about 300 mg/kg/dose. The present invention relates to the use of compounds of the invention for treatment and/or prevention of fatigue, including fatigue associated with diseases or treatments.Fatigue is a weariness or lack of energy that is generally not relieved by rest or sleep. Fatigue is a common side effect of many diseases and conditions, including depression, cancer, multiple sclerosis, Parkinson's disease, Alzheimer's disease, chronic fatigue syndrome, fibromyalgia, chronic pain, traumatic brain injury, AIDS, and osteoarthritis. Fatigue can also result from administration of some medications or therapies, such as chemotherapy, radiation therapy, bone marrow transplant, and anti-depressant medications. There have been few reports of effective treatments for fatigue.The present invention provides improved methods for treating or preventing fatigue, e.g., fatigue associated with diseases or treatments ...

DEUTERATED FORMS OF AMINOSTEROLS AND METHODS OF USING THE SAME

Described are deuterated forms of aminosterols, or a pharmaceutically acceptable salt thereof, wherein one or more hydrogen atoms at one or more positions selected from C1, C2, C3, C4, C5, C6, C7, C8, C9, C11, C12, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, and C27, are replaced with deuterium. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:(a) one or more hydrogen atoms at one or more positions selected from C2, C3, C4, C5, C6, C7, C8, C22, C23, C24, C25, C26, and C27, are replaced with deuterium; and/or(b) one or more hydrogen atoms at one or more positions selected from C3, C4, C5, C6, C7, C22, C23, C24, C25, C26, and C27, are replaced with deuterium; and/or(c) one or more hydrogen atoms at one or more positions selected from C4, C5, C7, C22, C23, C24, C25, C26, and C27, are replaced with deuterium; and/or(d) one or more hydrogen atoms at one or more positions selected from C1, C2, C3, C4, C5, C6, C7, C8, C11, C12, C16, C17, C18, C19, C20, and C21 are replaced with deuterium; and/or(e) all hydrogen atoms at positions C25, C26, and C27 are replaced with deuterium; and/or(f) all hydrogen atoms at positions C26 and C27 are replaced with deuterium.3. The compound of claim 1 , wherein:(a) any atom not designated as deuterium is present at its natural isotopic abundance; and/or(b) the deuterium incorporation at each designated deuterium atom is at least about 90%; and/or(c) the deuterium incorporation at each designated deuterium atom is at least about 95%; and/or(d) the deuterium incorporation at each designated deuterium atom is at least about 97%.4. The compound of claim 1 , wherein:(a) the compound has an isotopic enrichment factor selected from the group consisting of at least about 3500, at least about 4000, at least about 4500, at least about 5000, at least about 5500, at least about 6000, at least about 6333.3, at least about 6466.7, at least about 6600, and at least about 6633.3; and/or(b) the ...

INHIBITORS OF COGNITIVE DECLINE

Compounds that are central nervous system drug candidates for the treatment of cognitive decline and, more particularly, Alzheimer's disease are provided. Methods of treating, inhibiting, and/or abatement of cognitive decline and/or Alzheimer's disease with a compound or pharmaceutically acceptable salt of the invention are also provided. Also provided are methods of preparing the compounds/compositions of the invention. 152-. (canceled)54. (canceled)55. The method of claim 53 , wherein the method of inhibiting claim 53 , treating claim 53 , and/or abatement of cognitive decline and/or Alzheimer's disease comprises one or more of:(i) restoration of long term potentiation; and/or(ii) inhibiting, treating, and/or abatement of neurodegeneration; and/or(iii) inhibiting, treating, and/or abatement of general amyloidosis; and/or(iv) inhibiting, treating, and/or abatement of one or more of amyloid production, amyloid assembly, amyloid aggregation, amyloid oligomer binding, and amyloid deposition; and/or(v) inhibiting, treating, and/or abatement of the activity/effect of one or more of Abeta oligomers on a neuronal cell.56. The method of claim 53 , wherein the method of inhibiting claim 53 , treating claim 53 , and/or abatement of cognitive decline and/or Alzheimer's disease comprises inhibiting claim 53 , treating claim 53 , and/or abatement of the activity/effect of Abeta oligomers to a neuronal cell.57. The method of claim 53 , wherein the method of inhibiting claim 53 , treating claim 53 , and/or abatement of cognitive decline and/or Alzheimer's disease comprises inhibiting claim 53 , treating claim 53 , and/or abatement of binding of one or more of Abeta oligomers to a neuronal cell.5862-. (canceled)63. The method of claim 53 , wherein the cognitive decline is tested in an animal model of cognitive decline.64. The method of wherein the cognitive decline is a decline in learning as tested by a fear conditioning assay.66. The method of claim 65 , wherein the compound ...

CONFORMATIONALLY-PREORGANIZED, MiniPEG-CONTAINING GAMMA-PEPTIDE NUCLEIC ACIDS

Described are γ-PNA monomers, methodology for synthesizing them, and methodology for synthesizing PNA oligomers that incorporate them. 2. The compound of claim 1 , whereinZ is selected from the group consisting of iodine and hydroxyl;{'sub': 11', '2', '2', '2', 'x', '8', '12, 'Ris —CH—[O(CH)]—ORand Ris H, wherein x is an integer from 1 to 4 inclusive;'}{'sub': '5', 'Ris selected from the group consisting of hydrogen (H) and methyl; and'}{'sub': '8', 'Ris selected from the group consisting of hydrogen, methyl, ethyl, and t-butyl.'}3. The compound of claim 2 , wherein Z is hydroxyl claim 2 , Ris hydrogen claim 2 , Ris hydrogen and P is 9-fluorenylmethyloxycarbonyl (Fmoc) or t-butyloxycarbonyl (Boc).6. The compound of claim 5 , having an optical purity of at least 99% enantiomeric excess (ee).7. The compound of claim 1 , whereinZ is selected from the group consisting of iodine and hydroxyl;{'sub': 11', '12', '2', '2', '2', 'x', '8, 'Ris H and Ris —CH—[O(CH)]—OR, wherein x is an integer from 1 to 4 inclusive;'}{'sub': '5', 'Ris selected from the group consisting of hydrogen (H) and methyl; and'}{'sub': '8', 'Ris selected from the group consisting of hydrogen, methyl, ethyl, and t-butyl.'}8. The compound of claim 7 , wherein Z is hydroxyl claim 7 , Ris hydrogen claim 7 , Ris hydrogen and P is 9-fluorenylmethyloxycarbonyl (Fmoc) or t-butyloxycarbonyl (Boc).11. The compound of claim 10 , having an optical purity of at least 99% enantiomeric excess (ee).12. The compound of claim 1 , wherein Z is hydroxyl (—OH).13. The compound of claim 1 , wherein Z is iodine (I) claim 1 , 4-toluenesulfonate or methanesulfonate.15. The method of claim 14 , further comprising:c) contacting said compound of formula with a reagent selected from the group consisting of: methanesulfonyl chloride, 4-toluenesulfonyl chloride and sodium iodide. This application is a divisional of U.S. patent application Ser. No. 14/921,755, filed Oct. 23, 2015, which is a divisional of U.S. patent application Ser. ...

METHOD FOR PREPARATION OF (S)-N1-(2-AMINOETHYL)-3-(4-ALKOXYPHENYL)PROPANE-1,2-DIAMINE TRIHYDROCHLORIDE

The present invention relates to a novel method for preparing (S)—N-(2-aminoethyl)-3-(4-alkoxyphenyl)propane-1,2-diamine trihydrochloride. 3. The method of claim 1 , wherein step (1) is performed using tetrahydrofuran (THF) claim 1 , 1 claim 1 ,4-dioxane claim 1 , diethylether claim 1 , or a mixture thereof as a solvent.4. The method of claim 2 , wherein step (1-1) is performed at a temperature of 20° C. to 60° C.5. The method of claim 2 , wherein step (1-2) is performed at a temperature of −20° C. to 30° C.6. The method of claim 2 , wherein step (1-2) is performed by further comprising a Lewis acid.7. The method of claim 1 , wherein step (2) is performed using dimethylformamide as a solvent.8. The method of claim 1 , wherein step (2) is performed at a temperature of 70° C. to 100° C.10. The method of claim 9 , wherein step (3-2) is performed by further comprising a catalyst selected from 4-dimethylaminopyridine and iodine (I) claim 9 , or an alkaline substance selected from triethanolamide (TEA) claim 9 , N claim 9 ,N-diisopropylethylamine (DIEA) claim 9 , and NaHCO.11. The method of claim 1 , wherein step (3) is performed using acetonitrile claim 1 , toluene claim 1 , or a mixture thereof as a solvent.12. The method of claim 9 , wherein step (3-1) is performed at a temperature of 55° C. to 70° C.13. The method of claim 9 , wherein step (3-2) is performed at a temperature of 20° C. to 30° C.14. The method of claim 1 , wherein step (4) is performed using acetonitrile claim 1 , tetrahydrofuran claim 1 , toluene claim 1 , or a mixture thereof as a solvent.15. The method of claim 1 , wherein step (4) is performed at a temperature of 45° C. to 55° C.16. The method of claim 1 , wherein the reaction of step (5) is performed with trifluoroacetic acid claim 1 , hydrochloric acid claim 1 , methanolic hydrochloric acid claim 1 , or a mixture thereof.17. The method of claim 1 , wherein step (5) is performed using methanol claim 1 , dichloromethane claim 1 , tetrahydrofuran ...

NOVEL CATIONIC LIPIDS AND METHODS OF USE THEREOF

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. 232-. (canceled)33. A lipid particle comprising a cationic lipid or salt thereof of .3440-. (canceled)41. The lipid particle of claim 33 , wherein the lipid particle further comprises a therapeutic agent.4249-. (canceled)50. A pharmaceutical composition comprising a lipid particle of and a pharmaceutically acceptable carrier.51. A method for introducing a therapeutic agent into a cell claim 33 , the method comprising:{'claim-ref': {'@idref': 'CLM-00041', 'claim 41'}, 'contacting the cell with a lipid particle of .'}52. (canceled)53. A method for the in vivo delivery of a therapeutic agent claim 33 , the method comprising:{'claim-ref': {'@idref': 'CLM-00041', 'claim 41'}, 'administering to a mammal a lipid particle of .'}5455-. (canceled)56. A method for treating a disease or disorder in a mammal in need thereof claim 33 , the method comprising:{'claim-ref': {'@idref': 'CLM-00041', 'claim 41'}, 'administering to the mammal a therapeutically effective amount of a lipid particle of .'}5758-. (canceled) The present application claims priority to U.S. Provisional Application No. 61/334,104, filed May 12, 2010, and U.S. Provisional Application No. 61/384,050, filed Sep. 17, 2010, the disclosures of which are hereby incorporated by reference in their entirety for all purposes.Therapeutic nucleic acids include, e.g., small ...

Polyisocyanate Composition and Isocyanate Polymer Composition

The present invention relates to a polyisocyanate composition comprising, on the basis of the total mass of the polyisocyanate composition, 97 weight % or more of a polyisocyanate, and 2.0 mass ppm or more and 1.0×10mass ppm or less of a compound having at least one unsaturated bond in which the compound is a different compound from the polyisocyanate, or 5.0 mass ppm or more and 2.0×10mass ppm or less of at least one inactive compound selected from the group consisting of a hydrocarbon compound, an ether compound, a sulfide compound, a halogenated hydrocarbon compound, a Si-containing hydrocarbon compound, a Si-containing ether compound, and a Si-containing sulfide compound. 120-. (canceled)22. The composition according to claim 21 , further comprising a compound having at least one unsaturated bond claim 21 ,wherein the unsaturated bond is a carbon-carbon double bond or a carbon-oxygen double bond,the carbon-carbon double bond is not a carbon-carbon double bond that constitutes an aromatic ring, andsaid compound having at least one unsaturated bond and said compound represented by formula (1) are different.23. The composition according to claim 22 , wherein the compound having at least one unsaturated bond comprises a carbonic acid derivative.24. The composition according to claim 23 , wherein the carbonic acid derivative is at least one carbonic acid ester selected from the group consisting of dimethyl carbonate claim 23 , diethyl carbonate claim 23 , dibutyl carbonate claim 23 , dipentyl carbonate claim 23 , and dihexyl carbonate; or an N-unsubstituted carbamic acid ester.25. The composition according to claim 21 , further comprising at least one compound selected from the group consisting of a hydrocarbon compound claim 21 , an ether compound claim 21 , a sulfide compound claim 21 , a halogenated hydrocarbon compound claim 21 , a Si-containing hydrocarbon compound claim 21 , a Si-containing ether compound claim 21 , and a Si-containing sulfide compound.27. The ...

CONFORMATIONALLY-PREORGANIZED, MINIPEG-CONTAINING GAMMA-PEPTIDE NUCLEIC ACIDS

The present invention relates to γ-PNA monomers according to Formula I where substituent groups R, R, R, R, R, R, B and P are defined as set forth in the specification. The invention also provides methodology for synthesizing compounds according to Formula I and methodology for synthesizing PNA oligomers that incorporate one or more Formula I monomers. 5. The PNA monomer of claim 1 , wherein{'sub': 1', '2', '2', '2', 'q', '2', '2', '2', 'q', '3', '2', '2', '2', 'q', '2', '3', '2', '2', '2', 'q', '3', '3, 'Ris —CH(OCHCH)OH; —CH(OCHCH)OCH; —CH(OCHCH)OCHCH; or —CH(OCHCH)OC(CH);'}{'sub': '2', 'Ris H;'}{'sub': 3', '4', '5', '6, 'R, R, R, and Reach independently are H;'}P is selected from the group consisting of H, 9-fluorenylmethyloxy carbonyl (Fmoc), tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), tosylate (Ts), benzyl (Bn), allyloxycarbonyl (alloc), trityl (Trt), dimethoxytrityl (DMT), and monomethoxytrityl (MMT);n is 0, 1, or 2; andq is 1, 2, 3, 4, or 5.6. The PNA monomer of claim 5 , wherein P is H; n is 1; and q is 1 claim 5 , 2 claim 5 , or 3.7. The PNA monomer of claim 1 , wherein Rand Rare H; Ris H or —CH; Ris H or —CH; n is 1; and q is 1 claim 1 , 2 or 3.8. The PNA monomer of claim 7 , wherein P is 9-fluorenylmethyloxy carbonyl (Fmoc) or tert-butyloxycarbonyl (Boc).11. A PNA oligomer comprising the PNA monomer of .15. The PNA oligomer of claim 11 , wherein{'sub': 1', '2', '2', '2', 'q', '2', '2', '2', 'q', '3', '2', '2', '2', 'q', '2', '3', '2', '2', '2', 'q', '3', '3, 'Ris —CH(OCHCH)OH; —CH(OCHCH)OCH; —CH(OCHCH)OCHCH; or —CH(OCHCH)OC(CH);'}{'sub': '2', 'Ris H;'}{'sub': 3', '4', '5', '6, 'R, R, R, and Reach independently are H;'}P is selected from the group consisting of H, 9-fluorenylmethyloxy carbonyl (Fmoc), tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), tosylate (Ts), benzyl (Bn), allyloxycarbonyl (alloc), trityl (Trt), dimethoxytrityl (DMT), and monomethoxytrityl (MMT);n is 0, 1, or 2; andq is 1, 2, 3, 4, or 5.16. The PNA oligomer of claim 11 , ...

AMINO ACID DERIVATIVES

There are provided amino acid derivatives of formula V and VI as defined herein which are pyrrolysine analogs for use in bioconjugation processes. 2. A pyrrolysine analog of formula VI according to wherein b is 1 or 2.3. A pyrrolysine analog of formula VI according to wherein FG represents —N claim 1 , —CH═CH claim 1 , —CCH claim 1 , —COCH claim 1 , COOCH claim 1 , phenyl substituted by halogen or cyclooctyne.5. A mutant protein containing as non-natural amino acid one or more pyrrolysine analogs according to .6. A mutant protein according to which is conjugated via the one or more non-natural amino acids to one or more moieties selected from proteins claim 5 , cytotoxic agents claim 5 , drugs and polymers.7. A mutant protein according to which is conjugated to a PEG moiety.8. A mutant protein according to which is conjugated to an antibody moiety.9. A mutant protein according to which is conjugated to a cytotoxic agent moiety.10. A mutant protein according to which is conjugated to a drug moiety.11. A mutant protein containing as non-natural amino acid one or more pyrroly sine analogs according to .12. A mutant protein according to which is conjugated via the one or more non-natural amino acids to one or more moieties selected from proteins claim 11 , cytotoxic agents claim 11 , drugs and polymers.13. An antibody which contains as non-natural amino acid one or more pyrrolysine analogs according to in each heavy chain and/or light chain.14. An antibody according to which is conjugated via the one or more non-natural amino acids to one or more moieties selected from proteins claim 13 , cytotoxic agents claim 13 , drugs and polymers This application is a divisional of U.S. patent application Ser. No. 14/430,412, filed Mar. 23, 2015, now U.S. Pat. No. 9,670,521, which is the U.S. national phase application of International Patent Application No. PCT/EP2013/069888, filed Sep. 24, 2013, which claims priority to U.S. Provisional Application Nos. 61/705,116, filed Sep. 24, ...

CELL LINES

There is provided inter alia a process for stabilizing a eukaryotic cell line which expresses PylRS and tRNAPyl and which is suitable for incorporation of a gene encoding a target protein containing one or more non-natural amino acids encoded by a nonsense codon which comprises culturing said cell line under conditions in which the adverse effect of tRNAPyl expression on cell viability and/or cell growth is reduced or eliminated. 2. A process for stabilizing a eukaryotic cell line which expresses PylRS and tRNAPyl and is capable of incorporating a gene encoding a target protein comprising one or more non-natural amino acids encoded by an amber codon , the process comprising:(a) culturing the cell line in the presence of a target protein containing one or more non-natural amino acids encoded by a nonsense codon;(b) culturing the cell line in the presence of a decoy protein containing one or more non-natural amino acids encoded by a nonsense codon, wherein the decoy protein is expressed under the control of an inducible promoter; or(c) culturing the cell line wherein expression of tRNAPyl occurs under the control of a repressible promoter.32. A process according to claim (b) wherein the decoy protein is selected from Green fluorescence protein , Red Fluorescence Protein , Yellow Fluorescence Protein , Cyan Fluorescence Protein , blue fluorescence protein , albumin , SEAP , Actin , b-2 microglobulin , glutathione-s-transferase , IgG , and a poly amber containing peptide.4. A stable eukaryotic cell line obtained by the process of .5. A stable eukaryotic cell line according to which expresses PylRS and tRNAPyl and a decoy protein containing one or more non-natural amino acids encoded by a nonsense codon claim 4 , wherein the decoy protein is expressed under the control of an inducible promoter.6. A process for producing a stable eukaryotic cell line which is capable of expressing PylRS and tRNAPyl and incorporating a gene encoding a target protein containing one or more ...

TRIALKYL CATIONIC LIPIDS AND METHODS OF USE THEREOF

The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel, trialkyl, 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. 2. The lipid of claim 1 , wherein each of the alkyl chains has a length of from Cto C.3. The lipid of claim 1 , wherein at least one of the alkyl chains has a double bond.4. The lipid of claim 1 , wherein at least one of the alkyl chains has a cis double bond.5. (canceled)6. The lipid of claim 1 , wherein Xis selected from the group consisting of dimethylamino claim 1 , diethylamino and ethylmethylamino.7. (canceled)8. The lipid of claim 1 , wherein Y is an ester or ketal.9. The lipid of claim 1 , wherein Y is an optionally substituted carbamate.10. The lipid of claim 1 , wherein Y is an ether.11. The lipid of claim 1 , wherein Y is an optionally substituted amide.14. A lipid particle comprising a lipid of .15. The lipid particle of claim 14 , wherein the particle further comprises a non-cationic lipid.1618-. (canceled)19. The lipid particle of claim 14 , wherein the particle further comprises a conjugated lipid that inhibits aggregation of particles.2021-. (canceled)22. The lipid particle of claim 14 , wherein the particle further comprises a therapeutic agent.23. The lipid particle of claim 22 , wherein the therapeutic agent is siRNA or mRNA.2430-. (canceled)31. A pharmaceutical composition comprising a lipid particle of and a pharmaceutically acceptable carrier.32. A method for introducing a therapeutic agent into a cell claim 14 , the method comprising:{'claim-ref': {'@idref': 'CLM-00022', 'claim 22'}, 'contacting the cell with a lipid particle of .'}33. (canceled)34. A method for the in ...

CHEMICAL BLOWING AGENT AND THERMALLY EXPANDABLE THERMOPLASTIC COMPOSITION

A chemical blowing agent is described that includes at least one tertiary alkyl carbamate. The chemical blowing agent can be activated thermally and is suitable for foaming thermoplastic materials and can, for example, be incorporated into thermally expandable baffle and/or reinforcement elements, which can be used in automotive manufacturing and building insulation. 2. The blowing agent according to claim 1 , wherein said index n equals 2 and said radical A represents a linear or branched divalent hydrocarbon radical having 2 to 10 carbon atoms and which optionally contains one or more heteroatoms claim 1 , in particular in the form of ether oxygen.3. The blowing agent according to claim 1 , wherein said carbamate CA has a molecular weight of between 131 g/mol and 750 g/mol claim 1 , preferably between 131 g/mol and 500 g/mol claim 1 , more preferably between 131 g/mol and 450 g/mol.4. The blowing agent according to claim 1 , wherein at least 50% of said carbamate CA decomposes under gas release at a temperature of between 170° C. and 230° C. within 10 min.5. The blowing agent according to claim 1 , wherein said radicals R claim 1 , R claim 1 , and Rrepresent methyl groups.6. A method of manufacturing a carbamate CA suitable to be used in the chemical blowing agent according to claim 5 , comprising the reaction of a mono- or polyamine according to formula (II) with n equivalents di-tert-butyl dicarbonate claim 5 ,{'br': None, 'sup': '4', 'sub': 'n', 'Al\ue8a0NHR]\u2003\u2003(II).'}7. A method of manufacturing a carbamate CA suitable to be used in a chemical blowing agent according to claim 1 , comprising the reaction of a mono- or polyisocyanate according to formula (III) with n equivalents of a tertiary alcohol HO—C(R)(R)(R) claim 1 ,{'br': None, 'sub': 'n', 'Al\ue8a0NCO]\u2003\u2003(III)'}{'sup': 1', '2', '3, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein radicals A, R, R, and Rand index n have the same meaning as described in .'}8. A thermally ...

CELLULOSE ACYLATE FILM, NOVEL COMPOUND, POLARIZING PLATE AND LIQUID CRYSTAL DISPLAY DEVICE

A cellulose acylate film, which includes a compound denoted by general formula (I) below, the equivalent U of which, calculated as a value obtained by dividing the molecular weight of the compound by the number of divalent linking groups denoted by —O—C(═O)—NH— contained per molecule, is less than or equal to 515, wherein, in general formula (I), each of Land Lindependently denotes an optionally substituted alkylene group; each of Land Lindependently denotes a single bond, any one of or any combination of —O—, —NR—, —S— and —C(═O)—; Rdenotes a hydrogen atom or a substituent; each of n1 and n2 independently denotes an integer of 0 to 20, with at least either n1 or n2 being an integer of greater than or equal to 1. 2. The cellulose acylate film according to claim 1 , wherein the compound denoted by general formula (I) comprises 1 to 6 divalent linking groups denoted by —O—C(═O)—NH— per molecule.3. The cellulose acylate film according to claim 1 , wherein the molecular weight of the compound denoted by general formula (I) ranges from 230 to 2 claim 1 ,000.4. The cellulose acylate film according to claim 1 , wherein the compound denoted by general formula (I) is a compound denoted by general formula (I-1) below:{'br': None, 'sup': 3', '32', '31', '41', '42', '1, 'sub': n3', 'n4', 'm, '(Q-(L-L)-A-(L-L))-Z\u2003\u2003General formula (I-1)wherein, in general formula (I-1),{'sup': 31', '41, 'each of Land Lindependently denotes an optionally substituted alkylene group;'}{'sup': 32', '42', '1, 'each of Land Lindependently denotes a single bond, any one of or any combination of —O—, —NR—, —S—, and —C(═O)—;'}{'sup': '1', 'Rdenotes a hydrogen atom or a substituent;'}each of n3 and n4 independently denotes an integer of 0 to 20, with at least either n3 or n4 being an integer of greater than or equal to 1;{'sup': 31', '32', '41', '42', '31', '32', '41', '42, 'when L, L, L, and Lin a plurality of number, the plurality of L, L, L, and Lcan be identical or different;'}{'sup': '3', ' ...

AGONISTS THAT ENHANCED BINDING OF INTEGRIN-EXPRESSING CELLS TO INTEGRIN RECEPTORS

A method of enhancing binding of cells to an integrin-binding ligand comprises treating integrin-expressing cells in vitro with an agonist of integrin, wherein the integrin is selected from the group consisting of α4β1, α5β1, α4β7, αvβ3 and αLβ2, and contacting the treated cells with an integrin-binding ligand; integrin agonist compounds having the general formula I; methods of treating integrin-expressing cells with such agonists to enhance binding; and therapeutic methods comprising administering agonist-treated cells or agonist compounds to a mammal. 2. A compound of selected from the group consisting of N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(2-thienylmethyl)pentanediamide; N-(3-methoxybenzyl)-N claim 1 ,N′ claim 1 ,N′-tris(2-thienylmethyl)pentanediamide; N claim 1 ,N claim 1 ,N′-tris(2-thienylmethyl)pentanediamide; N′-[2-(2-thienyl)ethyl]-N claim 1 ,N-bis(2-thienylmethyl)pentanediamide; N-[2-(2-thienyl)ethyl]-N claim 1 ,N′ claim 1 ,N′-tris(2-thienylmethyl)pentanediamide; N claim 1 ,N-bis(pyridin-4-ylmethyl)-N′ claim 1 ,N′-bis(2-thienylmethyl)pentanediamide; N claim 1 ,N-bis(pyridin-3-ylmethyl)-N′ claim 1 ,N′-bis(2-thienylmethyl)pentanediamide; N claim 1 ,N-bis(3-methoxybenzyl)-N′ claim 1 ,N′-bis(2-thienylmethyl)pentanediamide; N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(4-methoxybenzyl)pentanediamide; N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(2-thienylmethyl)hexanediamide; N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(4-methoxybenzyl)hexanediamide; N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(3-methoxybenzyl)hexanediamide; N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(2-thienylmethyl)heptanediamide; 2 claim 1 ,2′-(1 claim 1 ,3-phenylene)bis[N claim 1 ,N-bis(2-thienylmethyl)acetamide]; N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(4-methoxybenzyl)heptanediamide; N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(2-thienylmethyl)octanediamide; (3E)-N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetrakis(2-thienylmethyl)hex-3-enediamide; 2 claim 1 ,2′-oxybis[N claim ...

PROPYL CATIONIC PEPTIDE LIPIDS, SYNTHESIS METHOD THEREOF, AND APPLICATION THEREOF

A class of propyl cationic peptide lipids is propyl cationic peptide lipid compounds having a general formula structure as follows. After the propyl cationic peptide lipids are dispersed in water, a cationic liposome with a particle size of approximately 100 nm is obtained. The cationic liposome can carry plasmid DNA (pDNA) or small interfering RNA (siRNA) into cells to realize the function of gene delivery, and is almost non-toxic to the cells. 2. The propyl cationic peptide lipid according to claim 1 , wherein Ris selected from C claim 1 , C claim 1 , C claim 1 , or Calkyl claim 1 , x is selected from 2 to 4.3. A method for synthesizing the propyl cationic peptide lipid according to claim 1 , comprising the following steps:1) preparing a peptide head intermediate by protecting amino group of amino acid with a protective reagent by means of orthogonal protection method: the amino acid being selected from Lys, Orn, Arg, His, Asp, Ala or Gly, the amino group protective reagent being di-tert-butyl dicarbonate (Boc2O), Fluorenylmethoxycarbonyl succinimide (Fmoc-OSu) or benzyl chloroformate (CbzCl), at a molar ratio of the protective reagent and the amino acid being 1:1 to 8:1, the reaction solvent being acetonitrile, toluene, acetone, tetrahydrofuran or water, the reaction time being 1 to 20 hours, and the reaction temperature being 0 to 100° C. After the reaction, the solvent being removed by rotary evaporation, followed by purification by means of recrystallization with a recrystallization solvent being an ethyl acetate/petroleum ether mixed solvent (v/v=3:1);2) protecting the amino group of 3-amino-1,2-propanediol with Fmoc-OSu protective reagent, after acylation with an acylating agent, reacting the resultant with alkyl amine, to prepare a disubstituted propyl long carbon chain intermediate: the acylating agent being carbonyl diimidazole, at a molar ratio of the acylating agent and 3-amino-1,2-propanediol being 1:1 to 3:1, after acylation, the molar ratio of 3- ...

Dental polyfunctional monomers and dental hydroxyl group-containing monomers

Provided are monomers useful for dental materials that include a compound in which a core and a specific terminal group are bonded to each other directly or via a linking group, wherein the core is a C 1-200 polyvalent organic group having a valence of not less than 3 containing an oxygen atom or a nitrogen atom in which an atom bonded to the terminal group or the linking group is the oxygen atom or the nitrogen atom; the terminal group is a specific (meth)acryloyl group-containing group, a (meth)acryloyl group, a C 1-20 hydrocarbon group or a hydrogen atom, and the terminal group needs to meet specific requirements; and the linking group is a specific divalent group, and when the compound contains a plurality of linking groups, the linking groups may be the same as or different from each other. Compositions, dental materials and kits are also provided.

Substituted benzyloxy-phenylmethylcarbamate derivatives

The present invention relates to novel substituted benzyloxy-phenylmethylcarbamate derivatives, processes for their preparation, and their use in medicaments, especially for the prophylaxis and treatment of diseases associated with Cold Menthol Receptor 1 (CMR-1) activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

(Meth)acrylic acid derivatives of tricyclo[5.2.1.02.6]decanes containing urethane groups

Die neuen Urethangruppen enthaltende (Meth)-acrylsäurederivate von Tricyclo[5.2.1.0<2.6>]decanen können durch Umsetzung von Hydroxyalkyl-(Meth)-acrylsäureester mit Diisocyanaten und nachfolgender Umsetzung mit Polyolen hergestellt werden. Die Verbindungen können für Dentalwerkstoffe verwendet werden. The new (meth) acrylic acid derivatives of tricyclo [5.2.1.0 <2.6>] decanes containing urethane groups can be prepared by reacting hydroxyalkyl (meth) acrylic acid esters with diisocyanates and subsequent reaction with polyols. The compounds can be used for dental materials.

(METH) ACRYLIC ACID ESTERS AND THEIR USE

URETHANE GROUPS CONTAINING (METH) ACRYLIC ACID DERIVATIVES FROM TRICYCLO (5.2.1.0 (UP ARROW) 2 (UP ARROW) (UP ARROW). (UP ARROW) (UP ARROW) 6 (UP ARROW)) DECANES

Compounds comprising perfluorinated group, photoinitiator group, and amide linking group

Compound are described comprising a perfluorinated group bonded to at least one terminal photoinitiator group with an organic linking group comprising at least one amide moiety. The compound typically comprises the (e.g. Michael addition) reaction product of i) a compound comprising an acryl group and a photoinitiator group; and ii) an amino functional perfluorinated compound. Also described is a composition comprising at least one free-radically polymerizable (e.g. fluorinated) monomer, oligomer, or combination thereof; and the described fluorinated photoinitiator compound and methods.

Urethane groups containing olefinically unsaturated isocyanates and their use as binders in coating compositions

A process for the preparation of olefinically unsaturated isocyanates containing urethane groups by reaction of a) an isocyanate component, consisting essentially of urethane group-free cycloaliphatic diisocyanates with b) an unsaturated alcohol component, consisting essentially of monohydric, olefinically unsaturated alcohols or mixtures of alcohols of this type while maintaining an NCO/OH equivalent ratio of 4 to 40 and subsequent distillative removal of distillable, unreacted starting isocyanates, the isocyanates thus obtainable and their use as binders for coating materials to be processed at room temperature as a single component.

NOVEL PHOTOCLEAVABLE MASS-TAGS FOR MULTIPLEXED MASS SPECTROMETRIC IMAGING OF TISSUES USING BIOMOLECULAR PROBES

The field of this invention relates to immunohistochemistry (IHC) and in situ hybridization (ISH) for the targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells for example, for research use and for clinical use such by pathologists (e.g., biomarker analyses of a resected tumor or tumor biopsy). In particular, the use of mass spectrometric imaging (MSI) as a mode to detect and map the biomolecules in tissues or cells for example. More specifically, the field of this invention relates to photocleavable mass-tag reagents which are attached to probes such as antibodies and nucleic acids and used to achieve multiplex immunohistochemistry and in situ hybridization, with MSI as the mode of detection/readout. Probe types other than antibodies and nucleic acids are also covered in the field of invention, including but not limited to carbohydrate-binding proteins (e.g., lectins), receptors and ligands. Finally, the field of the invention also encompasses multi-omic MSI procedures, where MSI of photocleavable mass-tag probes is combined with other modes of MSI, such as direct label-free MSI of endogenous biomolecules from the biospecimen (e.g., tissue), whereby said biomolecules can be intact or digested (e.g., chemically digested or by enzyme).

Processo para a preparacao de um 2,5-diamino-3-hidroxi-hexano substituido

Polymers

METHOD FOR THE PRODUCTION OF PEPTIDAMIDES BY SIDE-CHAIN TAPPING ON A SOLID PHASE

Icke inbyggbara, luktosa katalysatorer for polyuretansyntes

Способ получения производных азотистого иприта

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2017 142 725 A (51) МПК C07K 5/065 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2017142725, 06.05.2016 (71) Заявитель(и): ОНКОПЕПТАЙДС АБ (SE) Приоритет(ы): (30) Конвенционный приоритет: 08.05.2015 GB 1507903.1 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 08.12.2017 R U (43) Дата публикации заявки: 10.06.2019 Бюл. № 16 (72) Автор(ы): ВАЛЬСТРЁМ Никлас Хокан (SE), ВЕННЕРБЕРГ Йохан Андерс (SE) (86) Заявка PCT: (87) Публикация заявки PCT: WO 2016/180740 (17.11.2016) A Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3, ООО "Юридическая фирма Городисский и Партнеры" (57) Формула изобретения 1. Способ получения соединения (III) или его лишенного защиты продукта: R U A 2 0 1 7 1 4 2 7 2 5 (54) СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ АЗОТИСТОГО ИПРИТА 2 0 1 7 1 4 2 7 2 5 EP 2016/060242 (06.05.2016) Стр.: 1 R U A A (II) с хлоруксусной кислотой, в присутствии восстановителя; где PG представляет собой защитную группу, и R представляет собой OH в R U 2 0 1 7 1 4 2 7 2 5 2 0 1 7 1 4 2 7 2 5 (III) включающий взаимодействие соединения (II) Стр.: 2 соответствующим образом защищенной форме или . 2 0 1 7 1 4 2 7 2 5 R U A Стр.: 3 2 0 1 7 1 4 2 7 2 5 A R U 2. Способ по п.1, который осуществляют в присутствии восстановителя, выбранного из группы, состоящей из борана, комплекса боран-основание по Льюису, боргидрида, гидрида металла и Н2, в присутствии металлического катализатора. 3. Способ по п.2, где восстановителем является BH3 или боран-диметилсульфид. 4. Способ по любому из пп.1-3, где PG выбран из группы, состоящей из метилоксикарбонила, этилоксикарбонила, 9-флуоренилметилоксикарбонила, третбутилоксикарбонила, бензилоксикарбонила, p-метоксибензилоксикарбонила, 1адамантилоксикарбонила, p-бромбензилоксикарбонила, трифторацетила, хлорацетила, фенилацетила, бензацетила, p-толуолсульфонила, 2-нитробензолсульфонила, третбутилсульфонила, 2- или 4-нитробензолсульфонила ...

Synthesis of 2-oxazolidinone derivatives in single reactor

FIELD: organic chemistry, chemical technology. SUBSTANCE: invention proposes the improved method of synthesis of (S)-4-{[3-[2-(dimethylamino)-ethyl]-1H-indole-5-yl]-methyl}-2-oxa-zolindinone that involves the following stages: (a) formation of carbamate of the formula (III) from methyl-4-nitro-(L)-phenylalaninate hydrochloride; (b) reduction of compound of the formula (III) to yield methyl-(S)-N-butoxy-carbonyl-4-aminophenylalaninate of the formula (IV) ; (c) reduction of ester methyl group in compound of the formula (IV) to yield (S)-N-butoxycarbonyl-4-aminophenylalanilol of the formula (V) ; (d) ring closure in compound of the formula (V) to yield (S)-4-aminobenzyl-2-oxazolidinone hydrochloride of the formula (VII) ; (e) formation of diazonium salt from compound of the formula (VI) and the following reduction and yielding (S)-4-(4-hydrazinobenzyl)-2-oxazolidinone hydrochloride hydrazine of the formula (VII); f) Fischer's reaction of compound of the formula (VII) to yield (S)-4-{[3-[2-(dimethylamino)-ethyl] -1H-indole-5-yl] -methyl} -2-oxazolidinone. The end compound is agonist of 5-HT 1 -like receptors that are used effectively for treatment of patients suffering with migraine. EFFECT: improved method of synthesis, increased yield and purity of end product, simplified technology. 25 cl, 4 ex 9481491 С ПЧ с» РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (13) ВИ’ 2 167 875 ^С2 5) МК С 070 413/06, 263/20, С 07 С 219/06, 219/32, 215/06//(С 07 0 413/06, 263:20, 209:14) (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 98104085/04, 02.08.1996 (24) Дата начала действия патента: 02.08.1996 (30) Приоритет: 07.08.1995 СВ 9516145.1 (43) Дата публикации заявки: 20.12.1999 (46) Дата публикации: 27.05.2001 (56) Ссылки: КЦ 2110517 СУ, 10.05.98 СВ 1386613 А, 12.03.15. СВ 1478108 А, 29.06.77. (85) Дата перевода заявки РСТ на национальную фазу: 10.03.1998 (86) Заявка РСТ: СВ 96/01885 (02.08.1996) (87) Публикация РСТ: М/О 97/06162 (20.02.1997) ...

Method of producing fendiline

FIELD: chemistry. SUBSTANCE: present invention relates to organic chemistry and specifically to a method of producing fendiline by reductive amination of 3,3-diphenylpropanal with 1-phenylethane-1-amine. Mixture of reactants is reacted in atmosphere of converter gas with volumetric content of carbon monoxide of more than 20% during catalysis with salt of metal of group VIII in polar solvent at high pressure and temperature. EFFECT: what is presented is a new method of producing fendiline, which is simple, effective and suitable for use in industry. 6 cl, 1 tbl, 25 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 739 376 C1 (51) МПК C07C 209/02 (2006.01) C07C 211/27 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07C 209/02 (2020.08); C07C 211/27 (2020.08) (21)(22) Заявка: 2020124606, 24.07.2020 (24) Дата начала отсчета срока действия патента: Дата регистрации: Приоритет(ы): (22) Дата подачи заявки: 24.07.2020 (45) Опубликовано: 23.12.2020 Бюл. № 36 2 7 3 9 3 7 6 (54) СПОСОБ ПОЛУЧЕНИЯ ФЕНДИЛИНА (57) Реферат: Настоящее изобретение относится к области органической химии, а именно к способу получения фендилина восстановительным аминированием 3,3-дифенилпропаналя 1фенилэтан-1-амином. Смесь реактантов подвергают взаимодействию в атмосфере конвертерного газа с объемным содержанием монооксида углерода более 20% при катализе R U (56) Список документов, цитированных в отчете о поиске: SANCHEZ I. et al., Design and synthesis of substituted compounds containing the 1,4-benzodioxin subunit. New potential calcium antagonists, European Journal of Medicinal Chemistry, 2000, v. 35(7-8), p. 663-676. DF 2541184 A1, 15.04.1976. WO 2014031755 A1, 27.02.2014. US 20170071879 A1, 16.03.2017. US 20060142594 A1, 29.06.2006. US 6211244 B1, (см. прод.) (56) (продолжение): 03.04.2001. SU 603331 A3, 15.04.1978. US 20180193289 A1, 12.07.2018. Стр.: 1 солью металла VIII группы в полярном растворителе при повышенных давлении и температуре. ...

（メタ）アクリル酸エステル類

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

Method of producing nitrogen mustard derivatives

FIELD: chemistry. SUBSTANCE: invention relates to a method of producing compound (III) or a product which is not protected. Method involves reacting compound (II) with chloroacetic acid in the presence of a reducing agent. PG is a protective group and R is OH in an appropriately protected form or . Invention also relates to methods of producing other intermediate compounds which include the above method, as well as to intermediate compounds. , . EFFECT: invention can be used in synthesis of melphalan and melflufen. 25 cl, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07C 227/18 (2006.01) C07C 231/02 (2006.01) C07C 231/12 (2006.01) C07C 237/20 (2006.01) C07C 237/22 (2006.01) C07C 269/06 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА C07C 271/14 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ C07C 271/20 (2006.01) C07C 271/22 (2006.01) C07K 1/00 (2006.01) (12) (13) 2 715 233 C2 C07K 5/06 (2006.01) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07C 227/18 (2019.08); C07C 231/02 (2019.08); C07C 231/12 (2019.08); C07C 237/20 (2019.08); C07C 237/22 (2019.08); C07C 269/06 (2019.08); C07C 271/14 (2019.08); C07C 271/20 (2019.08); C07C 271/22 (2019.08); C07K 1/006 (2019.08); C07K 5/06078 (2019.08) 2017142725, 06.05.2016 (24) Дата начала отсчета срока действия патента: 06.05.2016 26.02.2020 Приоритет(ы): (30) Конвенционный приоритет: 08.05.2015 GB 1507903.1 (43) Дата публикации заявки: 10.06.2019 Бюл. № 16 (45) Опубликовано: 26.02.2020 Бюл. № 6 (86) Заявка PCT: R U 2 7 1 5 2 3 3 EP 2016/060242 (06.05.2016) (87) Публикация заявки PCT: WO 2016/180740 (17.11.2016) Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3, ООО "Юридическая фирма Городисский и Партнеры" (54) СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ АЗОТИСТОГО ИПРИТА (57) Реферат: Изобретение относится к способу получения соответствующим образом защищенной форме соединения (III) или его лишенного защиты или продукта, который может найти применение при синтезе мелфалана и мелфлуфена. Способ включает взаимодействие соединения (II) с хлоруксусной ...

Low-molecular conjugates for intracellular delivery of biologically active compounds

FIELD: biotechnology. SUBSTANCE: invention relates to application of a formula (III) ligand for preparation of conjugates of oligonucleotides and compositions based thereon, which can be used in medicine (III). A new effective ligand of formula (III) is provided for preparation of a conjugate in which the ligand for the asialoglycoprotein receptor is attached to an antisense oligonucleotide or siRNA via an amide bond to deliver the said antisense oligonucleotide or siRNA to the cell, respectively. A method for preparation of such a conjugate comprises conjugating a formula (III) ligand and an oligonucleotide or siRNA with NHC-6 hexylaminolinker at the 5'-end of the sense strand and O-acetate groups removal. EFFECT: increased compound efficiency. 3 cl, 6 dwg, 18 tbl, 52 ex

Fungicides

본 발명은 하기 화학식 (Ⅰ): The present invention is formula (I): [화학식 Ⅰ] [Formula I] [식 중, X는 H 또는 O - A + 이고 A는 하기 화학식 Ⅱ: [Wherein X is H or O - A + and A is the following formula II: [화학식 Ⅱ] [Formula II] 의 라디칼임]의 새로운 살진균성 활성 화합물, 만연되거나 만연되기 쉬운 위치에서 진균류를 퇴치하는 방법 및 농업적 조성물에 관한 것이다. Radicals of a novel fungicidal active compound, a method for combating fungi at an infested or prone position and agricultural compositions.

一釜法合成2－噁唑烷酮衍生物

本发明提供了制备(S)－4－{[3－[2－(二甲氨基)乙基]－1H－吲哚－5－基]甲基}－2－ 唑烷酮的改进方法,该方法包括a)由4－硝基－(L)－苯丙氨酸甲酯盐酸盐形成氨基甲酸酯(Ⅲ);b)还原式(Ⅲ)化合物,产生式(Ⅳ)化合物;c)还原式(Ⅳ)化合物中的甲酯基团,产生式(Ⅴ)化合物;d)环合式(Ⅴ)化合物,产生式(Ⅵ)化合物;e)形成式(Ⅵ)化合物的重氮盐,继之还原,产生式(Ⅶ)化合物;f)将式(Ⅶ)化合物进行费歇尔反应,产生(S)－4－{[3－[2－(二甲氨基)乙基]－1H－吲哚－5－基]甲基}－2－唑烷酮。

Low-molecular conjugates for intracellular delivery of nucleic acids

FIELD: chemistry. SUBSTANCE: disclosed are compounds and compositions based thereon, used in medicine, of formulae and , a nucleic acid (II), where Y is -(CH 2 ) 3 -; R 1 is -(C1-6)alkyl; or -(CH 2 ) m -phenyl, optionally substituted up to four times with a substitute selected from: -NO 2 , -CN, or a halogen; R 2 is hydrogen; -(CH 2 ) k -phenyl; -(C1-6)alkyl; -(CH 2 ) k -C(O)-NH 2 ; or -(CH 2 ) k -N-C(Ph) 3 . The phenyl rings are optionally substituted with -O-(C1-4)alkyl; R 3 is -NH-phenyl, wherein the phenyl is further substituted with a substitute independently selected from -(CH 2 )-OH or -(CH 2 )-O-C(O)-O-(4-nitrophenyl); k equals 1, 2, 3, 4, 5 or 6; m equals 1, 2, 3 or 4; and n equals 0 or 1, R a is -(CH 2 ) k -NH 2 ; R 1 , wherein the nucleic acid is a single-stranded RNA oligonucleotide. EFFECT: novel compounds for nucleic acid delivery in cells and compounds for production thereof. 10 cl, 653 ex, 19 tbl, 6 dwg РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C12N 15/87 C12N 15/11 A61K 48/00 A61K 31/713 A61K 47/18 (13) 2 582 235 C2 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2013134745/04, 04.08.2011 (24) Дата начала отсчета срока действия патента: 04.08.2011 Приоритет(ы): (30) Конвенционный приоритет: (43) Дата публикации заявки: 10.02.2015 Бюл. № 4 (45) Опубликовано: 20.04.2016 Бюл. № 11 (73) Патентообладатель(и): Ф.ХОФФМАНН-ЛЯ РОШ АГ (CH) (85) Дата начала рассмотрения заявки PCT на национальной фазе: 29.07.2013 2 5 8 2 2 3 5 (56) Список документов, цитированных в отчете о поиске: Quingmin Chen et al, Journal of Controlled Release, 2010, 144, 227-232. WO 2007138324 A2, 06.12.2007. WO 2007048244 A2, 03.05.2007. RU 2275936 C2, 10.05.2006. RU 2013134746 A1, 05.07.2012. R U 29.12.2010 US 61/427,845 (72) Автор(ы): ХАДВИГЕР Филипп (DE), ХОФФМАНН Торстен (DE), ЯН-ХОФМАНН Керстин (DE), КИТАС Эрик А. (CH), ЛЬЮИС Дэвид Л. (US), МОР Петер (CH), МЮЛЛЕР Ханс Мартин ...

Small molecule conjugates for intracellular delivery of nucleic acids

本发明提供了化合物用于递送核酸的用途和这些化合物与核酸、特别是siRNA的缀合物。本文还公开了稳定的siRNA，其在与所述化合物共价连接并与递送聚合物组合施用来实现体内mRNA敲减时有用。具体而言，本发明提供了式(I)化合物用于递送核酸的用途。

Polyisocyanates containing allophanate groups

本发明涉及新的以异佛尔酮二异氰酸酯为基础的含脲基甲酸酯基团的多异氰酸酯，以及它们的用途。

Small molecule conjugates for intracellular delivery of biologically active compounds

본 발명은 신규한 화합물 및 생물학적 활성 물질의 전달에 유용한 이러한 화합물의 접합체를 제공한다 또한 전달 중합체에 공유적으로 부착될 때 생체내 mRNA 녹 다운을 달성하기에 특히 유용한 화학적으로 안정화된 siRNA 에 대한 신규한 디자인 기준이 본원에 공개되어 있다.