КРИСТАЛЛИЧЕСКИЕ КОМПЛЕКСНЫЕ СОЕДИНЕНИЯ ПРОИЗВОДНЫХ МОРФОЛИНА С КАРБОНОВЫМИ КЕТОКИСЛОТАМИ В КАЧЕСТВЕ ИНГИБИТОРОВ КОРРОЗИИ, СПОСОБ ИХ ПОЛУЧЕНИЯ, СОСТАВ ДЛЯ ПОКРЫТИЯ И СПОСОБ ЗАЩИТЫ ОТ КОРРОЗИИ

Предложены кристаллические комплексные соединения формулы I, где R1, R2, R3, R4, R5 независимо друг от друга представляют водород, галоген, C1-C15-алкил или С6-С10 -арил, причем по меньшей мере один из радикалов R1-R5 обозначает водород, галоген или С1-C15-алкил, R10 представляет С1-C15 -алкил, a m обозначает целое число 2, которые могут быть использованы в качестве ингибиторов коррозии в составах для покрытия металлических поверхностей. Также раскрыты состав для покрытия, способ для защиты металлического субстрата от коррозии и способ получения соединений. Изобретение может быть применено в покрытиях для защиты металлических поверхностей. 5 с. и 10 з.п. ф-лы, 11 табл.

ФУНГИЦИДНАЯ КОМПОЗИЦИЯ

Использование: сельское хозяйство, средство защиты растений. Сущность: композиция содержит 1-[2-(2,4-дихлорфенил) -4пропил-1, 3-диоксолан-2-ил-метил] -1H-1,2,4-триазол и кумолсульфонат общей ф-лы, где m- 0 или 1 при массовом соотношении компонентов, равном 1:(1,6-3,8). Структура ф-лы 2 табл.

Способ получения производных пинана в виде оптически активных изомеров

Способ получения производных нафтиридина или их солей

Фунгицидный состав

Способ получения рацемических или оптически активных производных пиперазина

Способ получения пентациклических соединений

Способ получения @ -кофигурированных замещенных фенилпропанола

СПОСОБ ПОЛУЧЕНИЯ S-КОНФИГУРИРОВАННЫХ ЗАМЕЩЕННЫХ ФЕНИЛПРОПАНОЛА общей формулы Б -( Нг- clH- ciHzон. тГ ОНз где R- водород или метоксил, водород, трет-бутил, третбутоксил или метоксил отличающийся тем, что, с целью получения (-) -энантиомеров -целевых соединений, соответствующее замещенное коричного альдегида подвергают микробиологическому гидрированию с помощью дрожжей СО Saccharomyces cerevisiae : при 1040°С под воздействием аэрации возс духом в присутствии сахарозы с последуюр ей экстракцией полученного продукта хлористым метиленом и вьщелением целевого продукта упариванием. со 00 СП ...

Фунгицидная композиция

Verfahren zur Herstellung von therapeutisch wirksamen tertiaeren Aminen

PHENOXYALKANCARBONSAEUREDERIVAT, VERFAHREN ZU SEINER HERSTELLUNG UND ARZNEIMITTEL

Verfahren zur Herstellung von ungesättigten Aminen

VERFAHREN ZUR HERSTELLUNG VON AMOROLFIN

ISOPRENOID AMINES

1-AMINOMETHYLACE-NAPHTHENES AND THEIR PRODUCTION

Improvements in or relating to amines and aminonitriles and preparation thereof

An aminonitrile of formula where R is an aryl thienyl pyridyl or furyl group, Y is an alkylene bridge of 2-3 carbon atoms, -N=B is an aliphatic tertiary amino group, and R1 is cyclopentenyl or cyclohexenyl is prepared by treatment of where A is cyclopentylidene or cyclohexylidene with the compound Halogen-Y-N=B in the presence of a strong base. The resultant aminonitrile may be heated with a suspension of sodamide in an inert solvent to give an amine where the unsatisfied valencies of the carbon atom adjacent to the group R are satisfied by a cyclohexylidene group, a cyclopentylidene group, a cyclohexenyl group and hydrogen, or a cyclopentenyl group and hydrogen (the two different types of compound being tautomeric). The group -N=B may be dialkylamino or a cyclic amino group, e.g. morpholinyl, piperidinyl or pyrrolidinyl. Salts may be formed of the aminonitriles and the amines with acids or lower ...

Improvements in or relating to amine derivatives

The invention comprises free bases and their acid addition salts, the bases having the general formula wherein R1, R2 and R3 are alkyl radicals, R4 and R5 represent hydrogen or alkyl radicals and NZ is a heterocyclic radical. Such bases are obtained by reacting the appropriately substituted 1 - chloro - 3,3 - dialkylalkane with the base HNZ, either in a closed vessel or in solution in, for example, glycol or xylene. Starting materials of the formula R1R2R3C.CH2CH2Cl can be prepared by reacting ethylene with a tertiary alkyl halide of formula R1R2R3CCl. In example (1) 1-(3,3-dimethylbutyl)pyrrolidine is prepared by heating 3,3-dimethyl-1-chlorobutane with pyrrolidine. In a similar manner are prepared; (2) 4-(3,3-dimethylbutyl)morpholine; (3) 1 - (3,3 - dimethylbutyl)piperidine which are converted to their hydrochlorides. In further examples there are prepared (4) 4-(1,1,3,3-tetramethylbutyl)morpholine by reacting 2 - amino - 2,4,4 - trimethylpentane and bis(2 - chloroethyl ...

N-(2-Alkenyl)-Azabicyclo-Octanes and Nonanes

... 1,159,646. Therapeutic and moth proofing agents. UPJOHN CO. 13 July, 1967 [28 July, 1966], No. 32355/67. Headings A5B and A5E [Also in Division C2] Compounds effective as mothproofing agents are the fluosilicic acid salts of compounds of the formula where n is 0 or 1 and R is a C 3-5 2-alkenyl group. Therapeutic compositions effective as diuretics, pseudocholinesterase inhibiting agents, bactericides, cholesterol lowering agents, coccidiostats and anorexic agents comprise compounds of the above formula where n and R are as defined above or their acid addition salts with inorganic or organic acids in combination with pharmaceutical carriers, excipients, solvents or vehicles for administration as tablets, powders, capsules or as solutions or suspensions for oral or parenteral administration.

Aminoacetylenes and their production

The invention comprises compounds of formula R2N-C­C-NR2, wherein R is a monovalent hydrocarbon radical or R2 is an alkylene radical, and a process for making these and other aminoacetylene compounds, by maintaining at -25 DEG to 150 DEG C. a mixture in an aprotic organic solvent of (a) a compound of formula X1R11C=CHX or X1R1CH=CHXX1, wherein R1 is H or a monovalent hydrocarbon radical, R11 is H, halogen or a monovalent hydrocarbon radical and X and X1 are halogen atoms and (b) a compound containing the group -NRR111 wherein R111 is an alkali metal atom or a monovalent hydrocarbon radical, R is a alkylene radical, the free valency of the N being directly bonded to an alkali or alkaline earth metal atom or to a C atom (but when R111R is an alkylene radical, the free valency of the N being directly bonded to an alkali or alkaline earth metal atom or to a C atom (but when R111 is an alkali metal atom the free valency of the N is bonded to C). Examples describe the preparation of (1) t-Bu-C­C-NMe2 ...

DECAPRENYLAMINE DERIVATIVES

Tertiary (1-naphthyl)-alkylamines

Novel alkylamines of the general formula wherein R1 is a group of the formula -(CH2)2-N = R3 (wherein -N = R3 represents a saturated heterocyclic group which may contain a further hetero atom) and R2 represents any group represented by R1 or (when -N = R3 is a morpholino group) a hydrogen atom or an alkyl group containing at least 3 carbon atoms; and non-toxic acid addition salts thereof, are prepared by reacting a nitrile of the formula with an alkali metal amide or, when R2 is H, reducing an amide of the formula wherein -N = R3 is a morpholino group. Pharmaceutical compositions comprise as active ingredient a compound of the first general formula above and a pharmaceutical carrier or excipient. The compositions may be in solid or liquid form for oral administration or may be administered parenterally. The compositions are stated to have antiarrhythmic activity.

Therapeutically active phenylalkane derivatives

The invention comprises novel compounds of Formula (I) where R1 is hydrogen, halogen, C1- 4 alkyl C1- 4 haloalkyl, C1- 4 alkoxy, C1- 4 alkylthio, nitro or cyano; R2 is hydrogen or fluorine in the 21, 31, 51 or 61 positions; R3 i hydrogen, one or more halogen atoms, one or more C1- 4 alkyl groups, one or more C1- 4 haloalkyl groups, C1- 4 alkoxy, C1- 4 alkylthio, nitro or cyano; A is or (where R5 is hydrogen, C1- 4 alkyl, or C2- 4 alkenyl); and X is COOR4 (where R4 is hydrogen or C1- 4 alkyl), CH2OH or CONR6R7 (where R6 and R7 are hydrogen or C1- 4 alkyl); together with non-toxic organic and inorganic salts of the compounds in which X is COOH; provided (1) R1, R2 and R3 are all hydrogen, only when A is , (2) A-X is not CH2COOH when simultaneously R1 and R2 are hydrogen and R3 is 3-methyl, and (3) R5 is not hydrogen when R1 is a substituent in the 4-position. The acetic acids may be prepared from 4-acetylbiphenyls ...

9,10-DIHYDRO-9,10-METHANOANTHRACENE N-OXIDE DERIVATIVES AND THE PRODUCTION THEREOF

ANTI-INFLAMMATORY SUBSTITUTED PHENYLACETIC ACIDS

A therapeutic composition containing an n-benzhydryl-n-benzyl piperazine derivative

Piperazine derivatives of the formula where X is hydrogen or halogen, e.g. chlorine, and Y is hydrogen or lower alkyl (C1 to C6) group e.g. meta-methyl, are prepared by alkylation of piperazine under reductive conditions with a benzophenone derivative and a benzyl halide in either order, and admixed with pyridoxin in therapeutic compositions.ALSO:A therapeutic composition comprises pyridoxine with a piperazine derivative of formula: where X is hydrogen or halide, and Y is hydrogen or a lower alkyl (C1 to C6) group. The piperazine derivative may be used in the form of a water soluble salt e.g. dihydrochloride or dihydrobromide; or a salt of a non-toxic organic acid, e.g. citric, tartaric, acetic, succinic, maleic, glycolic, gluconic, glutaric or saccharic acid. The pyridoxin may be used as the hydrochloride or as a water soluble salt e.g. citrate, tartrate or acetate. The composition contains from one quarter to two parts by weight of the piperazine ...

PARACETAMOL DERIVATIVES

... 1514225 Salts of paracetamol BOTTU 16 June 1975 [18 July 1974] 25554/75 Heading C2C The invention comprises piperazine salts of paracetamol of the formula wherein R 1 and R 2 each are H or C 1-4 alkyl and the preparation by reacting solutions of paracetamol with solutions of the appropriate piperazines. Pharmaceutical compositions, suitable for oral or parenteral administration, contain the above salts and pharmaceutically acceptable carriers or diluents.

Method for producing substituted 5-fluoro-1H-pyrazolopyridines

Sulfonamide derivatives for the treatment of diseases

Method for producing substituted 5-fluoro-1H-pyrazolopyridines

Sulfonamide derivatives for the treatment of diseases.

Method for producing substituted 5-fluoro-1H-pyrazolopyridines

Sulfonamide derivatives for the treatment of diseases

Novel morpholinyl derivatives useful as mogat-2 inhibitors

Novel morpholinyl derivatives useful as mogat-2 inhibitors

Method for producing substituted 5-fluoro-1H-pyrazolopyridines

Method of preparation of the diphénylalkylamines.

New derivatives of the naphtyridine and their method of preparation.

Sulfonamide derivatives for the treatment of diseases.

Process for the preparation of the tritylamines.

New derivatives of the dibenzocycloheptadiene and their preparation.

Method of preparation of derived from méthylamine.

Derived from piperazine méthanimine and their process from preparation.

Derived from morpholine.

Process for the preparation of compounds pentacyclic.

Method of preparation of new substituted pyrrolidines.

Sulfonamide derivatives for the treatment of diseases

Method for producing substituted 5-fluoro-1H-pyrazolopyridines

PROCEDURE FOR the PRODUCTION OF NEW PHENOXY ALKANE CARBONIC ACID DERIVATIVES OF 1-CINNAMYL-4 DIPHENYLMETHYLPIPERAZIN

PROCEDURE FOR the PRODUCTION OF NEW ONE 7,7-DIMETHYL-1-AMINOALKYL (2,2,1) BICYCLOHEPTANEN AND OF THEIR SAEUREADDITIONSALZEN

FUNGIZID

VERFAHREN ZUR HERSTELLUNG VON NEUEN N-BENZHYDRYL-N'-P-HYDROXYBENZYL-PIPERAZINEN UND IHREN SAUREADDITIONSSALZEN

VERFAHREN ZUR HERSTELLUNG VON NEUEN PIPERAZINDERIVATEN UND DEREN SALZEN

METHOD FOR SCREENING PLASTIC HOUSINGS AGAINST ELECTROMAGNETIC RADIATION

VERFAHREN ZUR HERSTELLUNG VON NEUEN N-BENZHYDRYL-N'-P-HYDROXYBENZYL-PIPERAZINEN UND IHREN SALZEN

VERFAHREN ZUR HERSTELLUNG DES NEUEN N1- PIPERONYL-N4-3,7,11-TRIMETHYL-2,6,10-DODECATRIENYLPIPERAZINS, SEINER GEOMETRISCHEN ISOMERE UND SALZEN DAVON

PROCEDURE FOR the PRODUCTION OF NEW n-BENZHYDRYL-N' P-HYDROXYBENZYL-PIPERAZINEN AND YOUR SOUR ADDITION SALTS

PROCEDURE FOR the PRODUCTION OF NEW ONES 1-AMINO OR 1-AMINOMETHYL-7,7-DIMETHYL-2,2,1-CYCLO HEPTANEN AS WELL AS OF THEIR ACID ADDITION SALTS

FUNGICIDE

PROCEDURES FOR THE PRODUCTION OF NEW ONE, BASIC SUBSTITUTED INDANDERIVATEN

VERB-MOVED UNTIL ARYL CARBINOL DERIVATIVES, COMPOSITIONS AND YOUR USE

CALCIUM CHANNEL BLOCKER WITH TWO BENZHYDRIL PARTS

FUNGICIDE MEANS

PHENYLALKYLAMINE AND THIS CONTAINING FUNGICIDES.

PIPERAZINYL AND PIPERIDINYLCYCLOHEXENE AND - CYCLOHEXANES.

PROCEDURE FOR the PRODUCTION OF NEW ONES 1 (1,3DIOXOLAN-2-YLMETHYL) - 1H-IMIDAZOLEN AND -1H-1,2,4 TRIAXOLEN AND THEIR SALTS

N, N' DISUBSTITUIERTE PIPERAZINE.

CYCLIC AMINE DESCENDANTS.

BETA NAPHTHYLALKYLAMINE ONE.

THERAPEUTIC USE AS HISTAMIN-H3 RECEPTOR LIGAND OF ALKYL AMINES, NO IMIDAZOLE CONTAINING

Procedure for the production of new N-substituted 1-Aminomethylindanen

ANTIPSYCHOTI N-ARALKYL CYCLI AMINES

Procedure for the production of new racemischen or optically active Piperazinderivaten and their Säureaddtionssalzen

PROCEDURES FOR THE PRODUCTION OF NEW ONE, BASIC SUBSTITUTED INDANDERIVATEN

PROCEDURE FOR THE PRODUCTION OF NEW SUBSTITUTED PHENYLESSIGSAUREN AND YOUR ESTERS

MEANS FOR THE ADJUSTMENT OF PLANT GROWTH

HALOPYRIDONE.

MUSCARIN ANTAGONIST

OPIOIDE DIARYLMETHYLPIPERAZINE AND - PIPERIDINE

Procedure for the production of new racemischen or optically active Piperazinderivaten as well as of their acid addition salts

Procedures for the production of new basic Dibenzocycloheptadienderivaten as well as of them pharmaceutical usable salts and quaternären ammonium derivatives

Procedure for the production of new Phenylcyclopropanderivaten and their salts

Procedure for the production of new Diarylcyclopropanderivaten and their salts

FUNGICIDAL COMPOSITIONS CONTAINING AMINE DERIVATIVES OF HYDRONAPHTHALENE AND INDENE

INTERMEDIATES USEFUL FOR SYNTHESIS OF 2-SUBSTITUTED-5-METHYL-PYRIDINES

Benzene compounds disubstituted with cyclic groups at the 1- and 2-positions

Novel MCHR1 antagonists and their use for the treatment of MCHR1 mediated conditions and disorders

Piperazine derivatives

Sulfonamide derivatives for the treatment of diseases

Indane

The invention relates to compounds of formula (I) wherein R, R, R, R, and q have the designations cited in patent claim 1. Said compounds can be used, inter alia, for the treatment of tumours.

Novel aryl-and heteroarylpiperazines

PALLADIUM COMPLEXES WITH HETEROCYCLIC LIGANDS

INTERMEDIATES USEFUL IN SYNTHESIS OF 2-HALO-5-METHYL-PYRIDINE

4-(diarylmethyl)-1-piperazinyl derivatives

NEW PIPERAZINE METHANIMINE DERIVATIVES

METHYLAMINE DERIVATIVES

Heterocyclic amines having colmodulin antagonist properties

CYCLOHEPTENE DERIVATIVES

NAPHTALENIC AMINOALKYL DERIVATIVES, THE ACID ADDITION SALTS THEREOF AND THE PROCESS FOR PREPARING SAME, AS WELL AS THE APPLICATION IN THERAPEUTICS OF THESE DERIVATIVES AND SALTS

1-SUBSTITUTED-4-(1,2-DIPHENYLETHYL)PIPERAZINE DERIVATIVES AND COMPOSITIONS CONTAINING THE SAME

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

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

Process for the preparation of perfluoroalkylcyano- or perfluoroalkylcyanofluoroborates

The invention relates to a process for the preparation of salts having perfluoroalkyltricyano- or perfluoroalkylcyanofluoroborate anions, ((per)fluoro)phenyltricyano- or ((per)fluoro)phenylcyanofluoroborate anions, phenyltricyanoborate anions which are mono- or disubstituted by perfluoroalkyl groups having 1 to 4 C atoms or phenylcyanofluoroborate anions which are mono- or disubstituted by perfluoroalkyl groups having 1 to 4 C atoms, by reaction of alkali metal trifluoroperfluoroalkylborate with trialkylsilyl cyanide and a subsequent salt-exchange reaction or by direct reaction of an organic trifluoroperfluoroalkyl borate with trialkylsilyl cyanide.

Synthesis of mse-framework type molecular sieves

A method of synthesizing a crystalline molecular sieve having an MSE framework type comprises crystallizing a reaction mixture comprising a source of water, a source of an oxide of a tetravalent element, Y, selected from at least one of silicon, tin, titanium, vanadium, and germanium, optionally a source of a trivalent element, X, a source of an alkali or alkaline earth metal, M, and a source of organic dications, Q, such as 3-hydroxy-1-(4-(1-methylpiperidin-1-ium-1 yl)butyl)quinuclidin-1-ium, 3-hydroxy-1-(5-(1-methylpiperidin-1-ium-1-yl)pentyl)quinuclidin-1-ium, 1,1′-(butane-1,4-diyl)bis(1-methylpiperidin-1-ium), 1,1′-(pentane-1,5-diyl)bis(1-methylpiperidin-1-ium), 1,1′-(hexane-1,6-diyl)bis(1-methylpiperidin-1-ium), and 1,1′-((3as,6as)-octahydropentalene-2,5-diyl)bis(1-methylpiperidin-1-ium).

Nicotinic receptor non-competitive antagonists

The present invention relates to compounds that modulate nicotinic receptors as non-competitive antagonists, methods for their synthesis, methods for use, and their pharmaceutical compositions.

Amination of Aryl Alcohol Derivatives

Embodiments of the invention provide methods and materials for chemical cross-coupling reactions that utilize aryl alcohol derivatives as cross-coupling partners. Embodiments of the invention include methods for the amination of aryl sulfamates and carbamates, which are attractive cross-coupling partners, particularly for use in multistep synthesis. Illustrative embodiments include versatile means to use simple derivatives of phenol as precursors to polysubstituted aryl amines, as exemplified by a concise synthesis of the antibacterial drug linezolid. 1. A method for making a cross-coupled compound comprising: combining together:an aryl alcohol derivative, wherein the aryl alcohol derivative comprises an aryl carbamate compound or an aryl sulfamate compound;an amine; anda transition metal catalyst, wherein the transition metallic catalyst comprises nickel or palladium;wherein the aryl alcohol derivative, the amine and the transition metal catalyst are combined so as to allow a cross-coupling reaction between the amine, the aryl alcohol derivative and the transition metal catalyst that results in the formation of the cross-coupled compound that comprises a C—N bond between a carbon atom present in the aryl alcohol derivative and a nitrogen atom present in the amine, in a yield of at least 25%;so that the cross-coupled compound is made.2. The method of claim 1 , wherein the cross-coupling reaction results in the formation of the cross-coupled compound in a yield of at least 50%.3. The method of claim 1 , wherein the aryl alcohol derivative comprises an aryl sulfamate compound.4. The method of claim 1 , wherein the amine comprises a secondary amine.5. The method of claim 1 , wherein the aryl alcohol derivative comprises a heteroatom.6. The method of claim 1 , wherein the transition metallic catalyst comprises nickel.7. The method of claim 1 , wherein the transition metal catalyst comprises an air stable Ni(II) precatalyst complex prior to its combination with the amine ...

PROCESS FOR THE PREPARATION OF A MONO-N-ALKYLPIPERAZINE

Process for the preparation of a mono-N-alkylpiperazine of the formula I 132-. (canceled)34. The process according to claim 33 , wherein the oxidic material comprises(a) copper oxide with a fraction in the range from 50≦x≦80% by weight, calculated as CuO,(b) aluminum oxide with a fraction in the range from 15≦y≦35% by weight and(c) lanthanum oxide with a fraction in the range from 2≦z≦20% by weight,in each case based on the total weight of the oxidic material after calcination, where: 80≦x+y+z≦100.35. The process according to claim 33 , wherein the oxidic material comprises(a) copper oxide with a fraction in the range from 55≦x≦75% by weight, calculated as CuO,(b) aluminum oxide with a fraction in the range from 20≦y≦30% by weight and(c) lanthanum oxide with a fraction in the range from 3≦z≦15% by weight, in each case based on the total weight of the oxidic material after calcination, where: 80≦x+y+z≦100.36. The process according to claim 33 , wherein the oxidic material comprises(a) copper oxide with a fraction in the range from 55≦x≦75% by weight, calculated as CuO,(b) aluminum oxide with a fraction in the range from 20≦y≦30% by weight and(c) lanthanum oxide with a fraction in the range from 3≦z≦15% by weight,in each case based on the total weight of the oxidic material after calcination, where: 95≦x+y+z≦100.37. The process according to claim 33 , wherein claim 33 , in step ii claim 33 , graphite is added in amounts in the range from 0.5 to 5% by weight claim 33 , based on the total weight of the oxidic material after calcination.38. The process according to claim 33 , wherein pulverulent copper and/or the copper flakes taken together are added in amounts in the range from 0.5 to 40% by weight claim 33 , based on the total weight of the oxidic material after calcination.39. The process according to claim 33 , wherein 0.5 to 5% by weight of graphite is added to the mixture resulting from step ii prior to the shaping in step iii claim 33 , based on the total weight ...

Process for the Preparation of a Mono-N-Alkypiperazine

Process for the preparation of a mono-N-alkylpiperazine of the formula I 132-. (canceled)34. The process according to claim 33 , wherein the catalytically active mass of the catalyst claim 33 , prior to its reduction with hydrogen claim 33 , comprises in the range from 0.4 to 4.0% by weight of oxygen-containing compounds of tin claim 33 , calculated as SnO.35. The process according to claim 33 , wherein the catalytically active mass of the catalyst claim 33 , prior to its reduction with hydrogen claim 33 , comprises in the range from 0.6 to 3.0% by weight of oxygen-containing compounds of tin claim 33 , calculated as SnO.36. The process according to claim 33 , wherein the catalytically active mass of the catalyst claim 33 , prior to its reduction with hydrogen claim 33 , comprises in the range from 5.0 to 35% by weight of oxygen-containing compounds of cobalt claim 33 , calculated as CoO.37. The process according to claim 33 , wherein the catalytically active mass of the catalyst claim 33 , prior to its reduction with hydrogen claim 33 , comprises in the range from 10 to 30% by weight of oxygen-containing compounds of cobalt claim 33 , calculated as CoO.38. The process according to claim 33 , wherein the catalytically active mass of the catalyst claim 33 , prior to its reduction with hydrogen claim 33 , comprises in the range from{'sub': 2', '3, '15 to 80% by weight of oxygen-containing compounds of aluminum, calculated as AlO,'}1.0 to 20% by weight of oxygen-containing compounds of copper, calculated as CuO, and5.0 to 35% by weight of oxygen-containing compounds of nickel, calculated as NiO.39. The process according to claim 33 , wherein the catalytically active mass of the catalyst claim 33 , prior to its reduction with hydrogen claim 33 , comprises in the range from{'sub': 2', '3, '30 to 70% by weight of oxygen-containing compounds of aluminum, calculated as AlO,'}2.0 to 18% by weight of oxygen-containing compounds of copper, calculated as CuO, and10 to 30% by ...

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

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

Diamine and meglumine salt forms of fatty acids

Provided herein are diamine salts of eicosapentaenoic acid and docosahexaenoic acid, processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds, and the uses of such compounds as agents for treating dyslipidemia, cardiovascular diseases such as cardiac arrhythmia, cardiac ischemia, myocardial infarction, cardiomyopathy, and stroke and obesity.

METHOD FOR PRODUCING N-SUBSTITUTED AMINE COMPOUNDS THROUGH CATALYZED ALKYLATION

The invention relates to a method for producing a N-substituted amine compound by catalyzed alkylation. The method uses amine and alcohol or two kinds of amines as the reaction materials, employs composite metal oxides catalyst at a reaction temperature of 80-180° C. to catalyze the reaction for 6-36 hours, so as to produce the N-substituted amine compound. The reaction condition of the method of the invention is relatively moderate, using a catalyst made of cheap non-noble metals, which is non-caustic and easy to be separated and reused. The reaction does not need any medium and has relatively high conversion rate and selectivity. 2. The method of claim 1 , wherein the molar ratio of Cu to Ni is from 10:1 to 1:10 claim 1 , and the molar ratio of Cu to Fe is from 10:1 to 1:10 in CuO—NiO—FeO.3. The method of claim 1 , wherein the molar ratio of Ni to Fe in NiO—FeOis from 10:1 to 1:10.4. The method of claim 1 , wherein the molar ratio of Cu to Fe in CuO—FeOis from 10:1 to 1:10.5. The method of claim 1 , wherein the molar ratio of Cu to Ni in CuO—NiO is from 10:1 to 1:10.6. (canceled)7. The method of claim 1 , wherein the mass ratio between the composite metal oxide catalyst and the amine is from 0.01:1 to 1.2:1.8. The method of claim 1 , wherein the composite metal oxide catalyst is produced by the following steps:{'sub': 3', '2', '3', '2', '3', '3', '3', '3, '1) adding an aqueous solution of any two or three nitrates selected from Cu(NO), Ni(NO), and Fe(NO), and an aqueous Al(NO)solution, to an aqueous alkali metal oxide or hydroxide solution, aqueous ammonia, or aqueous carbamide solution which functions as a precipitator to coprecipitate;'}2) after step 1), providing a crude catalyst by washing, drying in the air, calcining, and reducing in hydrogen gas;{'sub': 3', '4', '3', '4', '3', '4, '3) using an aqueous alkali metal hydroxide solution to remove any alumina in the crude catalyst obtained in steps 1) and 2) to provide a composite metal oxides catalyst CuO—NiO— ...

Therapeutic polyamine compositions and their synthesis

This invention relates to a process of synthesis and composition of open chain (ring), closed ring, linear branched and or substituted polyamines, polyamine derived tyrosine phosphatase inhibitors and PPAR partial agonists/partial antagonists via a series of substitution reactions and optimizing the bioavailability and biological activities of the compounds. Polyamines prevent the toxicity of neurotoxins and diabetogenic toxins including paraquat, methyphenyl pyridine radical, rotenone, diazoxide, streptozotocin and alloxan. These polyamines can be utilized to treat neurological, cardiovascular, endocrine acquired and inherited mitochondrial DNA damage diseases and other disorders in mammalian subjects, and more specifically to the therapy of Parkinson's disease, Alzheimer's disease, Lou Gehrig's disease, Binswanger's disease, Olivopontine Cerebellar Degeneration, Lewy Body disease, Diabetes, Stroke, Atherosclerosis, Myocardial Ischemia, Cardiomyopathy, Nephropathy, Ischemia, Glaucoma, Presbycussis, Cancer, Osteoporosis, Rheumatoid Arthritis, Inflammatory Bowel Disease, Multiple Sclerosis and as Antidotes to Toxin Exposure. 1. A method of treating degenerative diseases due to acquired mitochondrial DNA damage , redox damage to mitochondrial macromolecules and inherited mitochondrial genetic defects said method comprising the steps of:selecting a composition from a group consisting of predominantly linear tetraamines and polyamines linked by 1,3-propylene and/or ethylene groups, predominately branched tetraamines and polyamines linked by 1,3-propylene and/or ethylene groups, cyclic polyamines linked by 1,3-propylene and/or ethylene groups, combinations of linear, branched and cyclic polyamines linked by one or more 1,3-propylene and/or ethylene groups, substituted polyamines, polyamines derivatized to form tyrosine phosphatase inhibitor molecules with linear or branched chains attached, polyamine derivatives of 2,2′-diaminobiphenyl with linear or branched chains ...

Compositions and Methods Including Cell Death Inducers and Procaspase Activation

Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3. In embodiments, compositions are capable of activation of procaspase-3.

METHOD FOR PRODUCING TRIARYLORGANOBORATES

The invention relates to a process for preparing triaryl organoborates proceeding from organoboronic esters in the presence of an n-valent cation 1/n K, comprising the anhydrous workup of the reaction mixture and the use of the triaryl organoborates obtained as co-initiator in photopolymer formulations, holographic media and holograms. 1. Process for preparing triaryl organoborates of the formula 1/n KRB—R(IV) , where one equivalent of organoboronic ester of the formula B—R(OR)(OR) (I) is initially charged together with 1/n equivalents of salt K nX (II) and 3 equivalents of metal M in a solvent or a solvent mixture S1 , 3 equivalents of a haloaromatic R—Y (III) are added , an auxiliary L and optionally a second organic solvent or solvent mixture S2 is added and the compound 1/n K RB—R(IV) is separated off with the organic phase and{'sup': '1', 'sub': 1', '22', '3', '22', '3', '22', '5', '7', '7', '13, 'Ris an optionally hydroxyl- and/or alkoxy- and/or acyloxy- and/or halogen-substituted C- to C-alkyl, C- to C-alkenyl, C- to C-alkynyl, C- to C-cycloalkyl or C- to C-aralkyl radical,'}{'sup': 2', '3', '2', '3, 'sub': 1', '22', '3', '7, 'Rand Rare independently an optionally branched C- to C-alkyl radical or an optionally alkyl-substituted C- to C-cycloalkyl radical or Rand Rtogether form a 2-8-membered carbon bridge which is optionally substituted by alkyl and/or interrupted by oxygen atoms,'}{'sup': '4', 'sub': 6', '10', '1', '4', '1', '4, 'Ris a C- to C-aryl radical optionally substituted by at least one radical selected from halogen, C- to C-alkyl, trifluoromethyl, C- to C-alkoxy, trifluoromethoxy, phenyl and phenoxy,'}K is an organocation of valency n and having any substitution, based on nitrogen, phosphorus, oxygen, sulfur and/or iodine, and{'sup': 2', '3, 'L is an auxiliary that forms a complex of sparing solubility in S1 and/or S2 with M salts MY(OR), MY(OR) and MXY, where L is a Lewis-basic compound, especially selected from the group consisting of open chain ...

PIPERIDINE AND PIPERAZINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS AND CANCER

Disclosed are compounds of formula (I) (formula I), as antiviral agents, antineoplastic agents, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X and Y are independently CH or N, o is 0, 1 or 2, and E is absent or is (CRR)m, NH, or S, F is absent or is (CRR)n, C=O, or —SO—, G is absent or is (CRCR)r, H is absent or is C═O, or —SO2- and R, Ar, Arare as defined in the specification. These compounds are antiviral agents and are contemplated in the treatment of viral infections, for example, hepatitis C, or are antineoplastic agents. 2. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein X is CH and Y is N and 0 is 1.3. (canceled)4. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein E is (CRR) claim 1 , F is absent claim 1 , and m is 2 claim 1 , and H is absent and r is 1.5. (canceled)6. (canceled)7. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein Ris selected from C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , and C-Ccycloalkyl C-Calkyl.8. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein Ris selected from hydrogen claim 1 , cyclopentyl claim 1 , sec-butyl claim 1 , isopropyl claim 1 , cyclohexyl claim 1 , n-propyl claim 1 , n-butyl claim 1 , benzoyl claim 1 , methyl claim 1 , ethyl claim 1 , trideuteromethyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trideuteroethyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trifluoroethyl claim 1 , phenylsulfonyl claim 1 , and benzyl.9. The compound claim 1 , salt claim 1 , stereoisomers claim 1 , and mixtures comprising stereoisomers of claim 1 , wherein Ris selected from Caryl and C-Caryl C-Calkyl claim 1 , wherein the aryl is optionally substituted with one or more substituents selected from halo claim 1 , cyano claim 1 ...

ALL-SOLID SECONDARY BATTERY AND METHOD OF PREPARING THE SAME

An all-solid secondary battery includes a cathode layer including a cathode active material layer; an anode layer; and a solid electrolyte layer disposed between the cathode layer and the anode layer, wherein the anode layer includes an anode current collector and a first anode active material layer is disposed on the anode current collector, wherein the first anode active material layer includes an organic electrolyte and an anode active material that is capable of forming an alloy with lithium or a compound with lithium, and wherein the organic electrolyte includes an organic salt including an organic cation and an anion. 1. An all-solid secondary battery comprising:a cathode layer comprising a cathode active material layer;an anode layer; anda solid electrolyte layer disposed between the cathode layer and the anode layer,wherein the anode layer comprises an anode current collector and a first anode active material layer disposed on the anode current collector,wherein the first anode active material layer comprises an organic electrolyte and an anode active material that is capable of forming an alloy with lithium or a compound with lithium, andwherein the organic electrolyte comprises an organic salt comprising an organic cation and an anion.2. The all-solid secondary battery of claim 1 , wherein the organic cation comprisesat least one of an acyclic cation comprising a Group 15 element or a heterocyclic cation comprising 1 to 3 heteroatoms.6. The all-solid secondary battery of claim 1 , wherein the organic salt comprises:at least one of an ammonium cation, a pyrrolidinium cation, a pyridinium cation, a pyrimidinium cation, an imidazolium cation, a piperidinium cation, a pyrazolium cation, an oxazolium cation, a pyridazinium cation, a phosphonium cation, a sulfonium cation, or a triazolium cation; andat least one anion.8. The all-solid secondary battery of claim 1 , wherein the anion comprises at least one of BF claim 1 , PF claim 1 , AsF claim 1 , SbF claim 1 , ...

Novel morpholinyl derivatives useful as mogat-2 inhibitors

The present invention provides compounds of Formula I or a pharmaceutical salt thereof, methods of treating hypertriglyceridemia using the compounds; and a process for preparing the compounds.

PRODRUGS OF 4-((1R, 3S)-6-CHLORO-3-PHENYL-2,3-DIHYDRO-1H-INDEN-1-Y)-1-,2,2-TRIMETHYLPIPERAZINE AND 4-((1R,3S)-6-CHLORO-3-(PHENYL-D5)-2,3-DIHYDRO-1H-INDEN-1YL)-2,2-DIMETHYL-1 (METHYL-D3)PIPERAZINE

The present invention relates to prodrugs of 4-((1R,3S)-6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-yl)-1,2,2-trimethylpiperazine in the form of 1a and 1b; and 4-((1R,3S)-6-chloro-3-(phenyl-d)-2,3-dihydro-1H-inden-1-yl)-2,2-dimethyl-1-(methyl-d)piperazine in the form of 2a and 2b, wherein X—is a counter ion, or pharmaceutically acceptable salts thereof. The present invention also provides pharmaceutical compositions comprising prodrugs, or pharmaceutically acceptable salts thereof, of the invention. 2. The prodrug according to claim 1 , wherein R is linear or branched C-Calkyl claim 1 , or a pharmaceutically acceptable salt thereof.3. The prodrug according to claim 1 , wherein R is selected from the group consisting of methyl claim 1 , tertbutyl claim 1 , n-undecane and cyclohexylmethyl claim 1 , or a pharmaceutically acceptable salt thereof.4. The prodrug claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , according to claim 1 , wherein the pharmaceutically acceptable salt is selected from the group consisting of salts formed from hydrochloride acid claim 1 , hydrobromide acid claim 1 , phosphoric acid claim 1 , nitrous acid claim 1 , sulphuric acid claim 1 , benzoic acid claim 1 , citric acid claim 1 , gluconic acid claim 1 , lactic acid claim 1 , maleic acid claim 1 , succinic acid claim 1 , tartaric acid claim 1 , acetic acid claim 1 , propionic acid claim 1 , oxalic acid claim 1 , maleic acid claim 1 , fumaric acid claim 1 , glutamic acid claim 1 , pyroglutamic acid claim 1 , salicylic acid claim 1 , saccharin and sulfonic acids.5. The prodrug according to selected from the group consisting of (R)-1-(acetoxymethyl)-4-((1R claim 1 ,3S)-6-chloro-3-phenyl-2 claim 1 ,3-dihydro-1H-inden-1-yl)-1 claim 1 ,2 claim 1 ,2-trimethylpiperazin-1-ium claim 1 , (S)-1-(acetoxymethyl)-4-((1R claim 1 ,3S)-6-chloro-3-phenyl-2 claim 1 ,3-dihydro-1H-inden-1-yl)-1 claim 1 ,2 claim 1 ,2-trimethylpiperazin-1-ium claim 1 , (R)-1-(acetoxymethyl)-4-((1R claim 1 ,3S)-6-chloro-3 ...

PROCESS FOR PRODUCING N-METHYL OR N,N-DIMETYL AMINES

A process for producing N-methyl or N,N-dimethyl amines, which comprises using amine compound, nitro-containing compound or nitrile compound as a starting material, carbon dioxide as a methylating agent and hydrogen gas as a reducing agent, and allowing them to react in a sealed reactor for 6 to 48 h in a reaction medium at a reaction temperature of 80 to 180 ° C. in the presence of a composite catalyst, so as to provide N-methyl or N,N-dimethyl amines. The process of the present invention is simple and under relative mild reaction conditions. By means of the process of the invention, the target products can be prepared at low cost with a high yield. The catalysts used have a high catalytic activity and can be separated from the reaction system simply and reused. Furthermore, the whole process of the present invention is environmental-friendly and facilitates the cycling use of carbon dioxide. 1. A process for producing N-methyl or N ,N-dimethyl amines comprisingusing amine compound, nitro-containing compound or nitrile compound as a starting material, carbon dioxide as a methylating agent, and hydrogen gas as a reducing agent, and allowing them to react in a reaction medium in a sealed reactor for 6 to 48 h at a reaction temperature of 80 to 180° C. in the presence of a composite catalyst, to provide the N-methyl or N,N-dimethyl amines,wherein the composite catalyst is formed of oxides of at least two metals, or of oxide of at least one metal and at least another metal element, said metal or metal element is selected from the group consisting of aluminum, bismuth, zinc, tin, gold, silver, copper, nickel, palladium, platinum, iridium, rhodium, cobalt, iron, ruthenium, osmium, manganese, rhenium, chromium, molybdenum, tungsten, vanadium, titanium, zirconium, lanthanum, yttrium, cerium, magnesium, calcium and barium.2. The process according to claim 1 , wherein the molar ratio of the methylating agent to the starting material is 1:1˜20:1 and the molar ratio of the ...

Hydrogenation reaction catalyst used to hydrogenate amide compound and method for producing amine compound using same

A catalyst, which can be used even under mild conditions and also has durability so as to enable repeated use while maintaining high activity, and with which a reduction reaction for converting an amide compound into an amine compound can be carried out, is provided by means of an amide compound hydrogenation reaction catalyst characterized in that platinum and vanadium are supported on a carrier and a method for producing an amine compound using the same.

ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES

A compound having a structure of Formula I, 2. The compound of claim 1 , wherein at least one R comprises at least one donor group selected from the group consisting of carbazole claim 1 , diphenylamino claim 1 , phenoxazine claim 1 , phenothiazine claim 1 , dibenzoazasiline claim 1 , pyrrolidine claim 1 , piperidine claim 1 , phenoxide claim 1 , and methoxide.3. The compound of claim 1 , wherein at least one R comprises at least one acceptor group selected from the group consisting of cyano claim 1 , pyrazole claim 1 , imidazole claim 1 , triazole claim 1 , pyridine claim 1 , pyrimidine claim 1 , triazine claim 1 , aza-carbazole claim 1 , aza-dibenzofuran claim 1 , and aza-dibenzothiophene group.4. The compound of claim 1 , wherein each one of Zthrough Zis CR.5. The compound of claim 1 , wherein at least one of Zthrough Zis N.7. The compound of claim 1 , wherein at least two Rs comprise donor substituents claim 1 , and one R comprises an acceptor substituent; or at least two Rs comprise acceptor substituents claim 1 , and one R comprises a donor substituent.10. The OLED of claim 9 , wherein the organic layer is an emissive layer and the compound is a host.11. The OLED of claim 9 , wherein the organic layer is a blocking layer and the compound is a blocking material in the organic layer claim 9 , or organic layer is a transporting layer and the compound is a transporting material in the organic layer.12. The OLED of claim 9 , wherein the organic layer is an emissive layer and the compound is an emitter.13. The OLED of claim 12 , wherein the OLED emits a luminescent radiation at room temperature when a voltage is applied across the first organic light emitting device; wherein the luminescent radiation comprises a delayed fluorescent process.14. The OLED of claim 13 , wherein the organic layer further comprises a sensitizer; andwherein the sensitizer is a phosphorescent emitting material.15. The OLED of claim 9 , wherein the organic layer further comprises a ...

CHARGED ION CHANNEL BLOCKERS AND METHODS FOR USE

The invention provides compounds, compositions, methods, and kits for the treatment of pain, itch, and neurogenic inflammation. 2. The compound of claim 1 , wherein Xis —NHC(O)—.3. The compound of or claim 1 , wherein each of Rand Ris independently selected from H claim 1 , halogen claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and NRR; and each of Rand Ris independently selected from H claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and Cheteroalkyl; or wherein at least one Ris present.4. The compound of any one of - claim 1 , wherein Ris Calkyl optionally substituted with halogen claim 1 , Ccyclic alkyl claim 1 , aryl claim 1 , or heteroaryl.5. The compound of any one of - claim 1 , wherein Ris H or Calkyl optionally substituted with halogen claim 1 , Ccyclic alkyl claim 1 , aryl claim 1 , or heteroaryl.6. The compound of any one of - claim 1 , wherein Ris Calkyl optionally substituted with halogen claim 1 , Ccyclic alkyl claim 1 , aryl claim 1 , or heteroaryl.7. The compound of any one of - claim 1 , wherein said compound is a compound in Table 1.11. The compound of claim 10 , wherein each of Rand Ris Calkyl optionally substituted with halogen claim 10 , cyclic alkyl claim 10 , aryl claim 10 , or heteroaryl.12. The compound of or claim 10 , wherein each of R claim 10 , R claim 10 , and Ris independently selected from H claim 10 , halogen claim 10 , Calkyl claim 10 , and CF; or wherein at least one Ris present; or wherein at least one Ris present.13. The compound of any one of - claim 10 , wherein said compound is a compound in Table 2.16. The compound of claim 15 , wherein Xis —NHC(O)—17. The compound of or claim 15 , wherein n is 0 or 1.18. The compound of any one of - claim 15 , wherein each of R claim 15 , R claim 15 , and Ris independently selected from H claim 15 , Calkyl claim 15 , and NRR; and each of Rand Ris independently selected from H claim 15 , Calkyl claim 15 , Calkenyl claim 15 , Calkynyl claim 15 , and ...

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are neuroactive steroids of the Formula (I); or a pharmaceutically acceptable salt thereof, wherein, R, R, R, Rand A are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia. 151-. (canceled)53. The process of claim 52 , wherein the process is performed in a solvent.54. The process of claim 52 , wherein the solvent is tetrahydrofuran.55. The process of claim 52 , wherein the process occurs at room temperature. This application claims priority to Provisional Application No. 62/064,957, filed Oct. 16, 2014, the entire contents of which are incorporated herein by reference.Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials. When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization, e.g., a change of potential from −70 mV to −50 mV. This effect is mediated by postsynaptic nicotinic receptors which are stimulated by acetylcholine to increase membrane permeability to Na ions. The reduced membrane potential stimulates neuronal excitability in the form of a postsynaptic action potential.In the case of the GABA ...

BIS(PHOSPHINE)-CARBODICARBENE CATALYST COMPLEXES AND METHODS OF USING THE SAME

An organometallic complex of a tridentate bis(phosphine)-carbodicarbene ligand and a transition metal, is described. In some embodiments the ligand has the structure of Formula (I): The complexes are useful in methods of making an allylic amine carried out by reacting a 1,3-diene with a substituted amine in the presence of such an organometallic complex to produce by intermolecular hydroamination the allylic amine. 1. An organometallic complex , comprising:(a) a tridentate bis(phosphine)-carbodicarbene ligand, and(b) a transition metal.4. The complex of claim 1 , wherein said transition metal is selected from the group consisting of ruthenium claim 1 , nickel claim 1 , palladium claim 1 , platinum claim 1 , rhodium claim 1 , iridium claim 1 , cobalt claim 1 , iron claim 1 , silver claim 1 , gold claim 1 , and molybdenum.5. The complex of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , and Rare each independently selected alkyl or aryl.6. The complex of claim 2 , wherein at least one R′ is S-L- claim 2 , where S is a solid support and L is a linking group.7. The complex of claim 2 , wherein each R′ is independently hydrogen claim 2 , halo claim 2 , loweralkyl claim 2 , loweralkoxy claim 2 , or hydroxyl.8. A reaction mixture comprising an organometallic complex of claim 1 , a solvent claim 1 , a 1-3 claim 1 , diene substrate claim 1 , and a substituted amine substrate.11. A method of making an allylic amine claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'reacting a 1,3-diene with a substituted amine in the presence of an organometallic complex of in a catalytic amount to produce by intermolecular hydroamination said allylic amine.'}14. A tridentate bis(phosphine)-carbodicarbene pincer ligand. This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/979,749, filed Apr. 15, 2014, the disclosure of which is incorporated by reference herein in its entirety.The present invention concerns carbodicarbene ligands, ...

1,4-Disubstituted Piperidines, 1,4-Disubstituted Piperazines, 1,4-Disubstituted Diazepines, and 1,3-Disubstituted Pyrrolidine Compounds

The present invention is directed to 1,4-disubstituted piperidines, 1,4-disubstituted piperazines, 1,4-disubstituted diazepanes, and 1,3-disubstituted pyrrolidine compounds and their use. 2. The compound of formula (1) according to claim 1 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 1 , methyl claim 1 , deuteromethyl (CD) claim 1 , tritiomethyl (CT) claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , C-Cstraight chain or branched alkyl claim 1 , C-Ccycloalkyl claim 1 , C-Calkenyl (including cis and trans geometrical forms) claim 1 , benzyl claim 1 , phenylethyl claim 1 , amino claim 1 , N-methylamino claim 1 , N claim 1 ,N-dimethylamino claim 1 , carboxylate claim 1 , methylcarboxylate claim 1 , ethylcarboxylate claim 1 , propylcarboxylate claim 1 , isopropylcarboxylate claim 1 , carboxaldehyde claim 1 , acetoxy claim 1 , propionyloxy claim 1 , isopropionyloxy claim 1 , cyano claim 1 , acetyl claim 1 , propionyl claim 1 , formyl claim 1 , phenyl claim 1 , hydroxyl claim 1 , methoxy claim 1 , ethoxy claim 1 , propoxy claim 1 , isopropoxy claim 1 , thiol claim 1 , methylthio claim 1 , ethylthio claim 1 , propiothiol claim 1 , fluoro claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , trifluoromethyl claim 1 , vinyl claim 1 , allyl claim 1 , propargyl claim 1 , nitro claim 1 , azido claim 1 , isocyanate claim 1 , thioisocyanate claim 1 , and nitroso.3. The compound of formula (1) according to claim 1 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , C-Cstraight chain or branched alkyl claim 1 , C-Ccycloalkyl claim 1 , C-Calkenyl (including cis and trans geometrical forms) claim 1 , benzyl claim 1 , phenylethyl claim 1 , carboxylate claim 1 , methylcarboxylate claim 1 , ethylcarboxylate claim 1 , propylcarboxylate claim 1 , isopropylcarboxylate claim 1 , carboxaldehyde claim 1 , cyano claim 1 , acetyl ...

WATER-SOLUBLE COMPOSITION, PRODUCTION METHOD FOR CURED PRODUCT THEREOF, AND CURED PRODUCT THEREOF, AND ACYL PHOSPHINATE

Provided are: a water-soluble composition which has excellent storage stability and is adaptable to a wide range of light sources and capable of forming a highly fine pattern; a method of producing a cured product of the same; a cured product of the same; and an acylphosphinate. The water-soluble composition contains: an acylphosphinate (A) represented by Formula (I) below, wherein Xrepresents an aryl group having 6 to 15 carbon atoms; Xrepresents a linear alkyl group having 1 to 8 carbon atoms or the like; A represents an alkali metal ion or the like; and m represents a number of 1 to 3; and a compound (B) having a group represented by Formula (II) below, wherein Rrepresents a hydrogen atom or the like; Zrepresents an oxygen atom or the like; Rrepresents a hydrogen atom or the like; Zrepresents an alkylene group having 1 to 6 carbon atoms; n represents a number of 0 to 30; * means a bond; and, when the compound (B) has plural groups represented by Formula (II), plural Rs, Zs, Zs and n's are each optionally the same or different. 2. The water-soluble composition according to claim 1 , wherein Xin the Formula (I) is a 2 claim 1 ,4 claim 1 ,6-trimethylphenyl group.3. The water-soluble composition according to claim 1 , wherein claim 1 , in the Formula (I) claim 1 , Xis a phenyl group and A is NHYYY.4. The water-soluble composition according to claim 1 , wherein{'sup': m+', '+', '1', '2', '3, 'A in the Formula (I) is NHYYY, and'}{'sup': 1', '2', '3, 'at least one hydrogen atom of Y, Yand Yis substituted with a hydroxy group.'}5. The water-soluble composition according to claim 1 , wherein Zin the Formula (II) is —NR—.6. The water-soluble composition according to claim 1 , further comprising a coloring agent (C).7. A method of producing a cured product claim 1 , comprising curing the water-soluble composition according to by irradiation with light or heating.8. A cured product obtained from the water-soluble composition according to .10. The acylphosphinate according to ...

Fullerene Derivatives and Their Applications in Organic Photovoltaics

The present invention relates to new fullerene derivatives of formulae 1a-d, 2 and 3: method of synthesizing said derivatives, and applications thereof in organic photovoltaics, e.g., organic solar cells. In particular, the fullerene derivatives of the present invention are soluble in non-halogenated solvents such that an environmental-friendly and low-cost fabrication method for industrialization of solar cell based on the new fullerene derivatives is provided. An ink formulation for forming a thin film on a substrate of organic photovoltaics comprising at least one of the fullerene derivatives of the present invention is also provided. Greater than 3% power conversion efficiency of the organic solar cells (area=0.16 cm 2 ) formed based on the fullerene derivatives of the present invention with less pollution and lower cost in fabrication can be achieved in the present invention.

EMM-23 Molecular Sieve Material, Its Synthesis and Use

A new molecular sieve material is designated as EMM-23 and has, in its as-calcined form, an X-ray diffraction pattern including the following peaks in Table 1: 114-. (canceled)16. The organic nitrogen compound of claim 15 , wherein said organic nitrogen compound is 1 claim 15 ,5-bis(N-propylpyrrolidinium)pentane dication.20. The organic nitrogen compound of claim 19 , wherein said organic nitrogen compound is 1 claim 19 ,6-bis(N-propylpyrrolidinium)pentane dication. This application claims priority to U.S. Patent Application No. 61/514,939 filed Aug. 4, 2011 and EP Application No. 11181734.2, filed Sep. 19, 2011, the disclosures of which are incorporated herein by reference in their entireties.This invention relates to a novel molecular sieve material, designated as EMM-23, its synthesis, its use as an adsorbent, and a catalyst for hydrocarbon conversion reactions.Molecular sieve materials, both natural and synthetic, have been demonstrated in the past to be useful as adsorbents and to have catalytic properties for various types of hydrocarbon conversion reactions. Certain molecular sieves, zeolites, AIPOs, mesoporous materials, are ordered, porous crystalline materials having a definite crystalline structure as determined by X-ray diffraction (XRD). Within the crystalline molecular sieve material there are a large number of cavities which may be interconnected by a number of channels or pores. These cavities and pores are uniform in size within a specific molecular sieve material. Because the dimensions of these pores are such as to accept for adsorption molecules of certain dimensions while rejecting those of larger dimensions, these materials have come to be known as “molecular sieves” and are utilized in a variety of industrial processes.Such molecular sieves, both natural and synthetic, include a wide variety of positive ion-containing crystalline silicates. These silicates can be described as rigid three-dimensional framework of SiOand Periodic Table Group 13 ...

ARYLATION OF ALIPHATIC AMINES

The invention relates to a method for arylation of amines, such as aliphatic amines by reaction of aryl-halogens, e.g. chloro- or fluorobenzene derivatives without strongly electron withdrawing substituents in the presence of a strong base. 1. A method for preparing an arylated amine , said method comprising the steps of{'sub': '2', 'a. Providing a nucleophile, wherein said nucleophile comprises an —NH— or an —NHgroup directly linked to only non-aromatic carbon atoms or a salt of said nucleophile;'}b. Providing an electrophile, wherein said electrophile is aryl substituted with at least two substituents, wherein the first substituent is halogen and the second substituent and any further optional substituent(s) are selected from the group consisting of halogen, aryl, substituted aryl, alkenyl, substituted alkenyl, heteroalkenyl, alkyl, substituted alkyl, heteroalkyl, alkoxy, substituted alkoxy, amino, thioalkyl, substituted thioalkyl, thioaryl, substituted thioaryl, heteroaryl, and phosphinyl, with the proviso that said aryl is substituted with at the most 4 halogens;c. Providing a base, wherein the corresponding acid has a pKa above 29 in DMSO and/or a pKa above 25 in THF;d. Providing an organic solvent that only contain protons with a pKa above 32 in DMSO.e. Reacting said nucleophile with said electrophile in said organic solvent in the presence of the base, thereby obtaining an arylated amine consisting of said aryl, wherein the first substituent is substituted by said amine;f. Optionally purifying the arylated amine,wherein steps a., b., c. and d. may be performed in any order.2. The method according to claim 1 , wherein step e. is performed in the absence of a transition metal catalyst.3. The method according to claim 1 , wherein step b. consists of providing an electrophile claim 1 , wherein said electrophile is aryl substituted with at least two substituents claim 1 , wherein the first substituent is halogen and the second substituent and any further optional ...

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF BENZO[B]THIOPHENE COMPOUNDS

A process for preparing compounds of formula (I), or a salt or solvate thereof, including Brexpiprazole, which process comprises cyclization of a compound of formula (II) or (III), or a salt or solvate thereof. The invention also refers to intermediates of said process. 5. Process according to claim 1 , wherein Rand Rare —CHO.7. Process according to claim 1 , wherein the cyclization of a compound of formula (II) or (III) claim 1 , or a salt or solvate thereof claim 1 , is carried out in the presence of an acid.9. Process according to claim 1 , wherein the compound of formula (I) is selected from (l-benzothiophen-4-yl)piperazine and Brexpiprazole claim 1 , or a salt or solvate thereof.1314-. (canceled) The invention relates to a process for preparing benzo[b]thiophene compounds that can be used to obtain therapeutically useful compounds, such as Brexpiprazole.Brexpiprazole, discovered by Otsuka, is a dopamine D2 receptor partial agonist. It has been recently approved by the FDA for the treatment of schizophrenia and as an adjunctive therapy for the treatment of major depression.The chemical name of Brexpiprazole is (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one), and is represented by the following formula:The synthesis of this compound was first disclosed in EP 1869025 by a process comprising palladium-catalyzed cross-coupling of non-commercial 4-bromo-benzo[b]thiophene and piperazine, followed by substitution of the piperazine with the butoxy-quinolinone derivative (Reference Example 30 and Example 1).In addition to being expensive, the Pd-catalyzed cross-coupling reaction is not clean and gives rise to a product with reduced purity, as acknowledged by the applicant in the subsequent patent application WO 2013/015456.WO 2013/015456 discloses a similar method for preparing Brexpiprazole, but starting from 4-chloro-benzo[b]thiophene and using smaller amounts of Pd and phosphines to cheapen the process (Examples 1-4). However, obtaining 4- ...

Organo-1-oxa-4-azonium cyclohexane compounds

Novel 1-oxa-4-azonium cyclohexane salts are described. These compounds can be used as structure directing agents, and they overcome many of the typical problems associated with OSDA synthesis and subsequent zeolite synthesis. Methods for synthesis of the 1-oxa-4-azonium cyclohexane salts from a variety of starting materials are also described. A substituted hydrocarbon is added to water to form a mixture, and a 1-oxa-4-azacyclohexane derivative is then added. The reaction mixture stirred until a solution containing the 1-oxa-4-azonium cyclohexane salt is obtained.

Preparation Of Difluoro Chelato Borate Salts

A process for preparing a difluoro chelato borate salt comprising an anion A of formula (I) 2. The process according to claim 1 , wherein the total content of additional sources for F-atoms is less than 50 mol.-% based on the total amount of BF-source (a).3. The process according to claim 1 , wherein the volatile reaction products are removed during and/or after step (i).4. The process according to claim 1 , wherein an organic solvent or solvent mixture (e) is present in the reaction mixture of step (i).5. The process according to claim 1 , wherein the BFsource (a) is selected from BF claim 1 , BFhydrate claim 1 , BFetherates claim 1 , BF-alcohol adducts claim 1 , BF-acetonitril adduct claim 1 , BF-acetic acid adduct claim 1 , and BF-amine adducts.6. The process according to claim 1 , wherein the dihydric compound (b) is selected from 1 claim 1 ,2-diols claim 1 , 1 claim 1 ,2-dicarboxylic acids claim 1 , and 1 claim 1 ,2-hydroxycarboxylic acids.7. The process according to claim 1 , wherein the dihydric compound (b) is selected from oxalic acid claim 1 , salicylic acid claim 1 , and phthalic acid.8. The process according to claim 1 , wherein the second boron source (c) is selected from boric acid claim 1 , B(OC-Calkyl) claim 1 , B(OC-C(hetero)aryl) claim 1 , and ammonium and alkali metal salts of borate complexes of the dihydric compound used as component (b).9. The process according to claim 1 , wherein the dihydric compound (b) is oxalic acid and the second boron source (c) is selected from boric acid claim 1 , lithium bis(oxalato) borate claim 1 , triethylammonium bis(oxalato)borate claim 1 , and mixtures thereof.10. The process according to claim 1 , wherein the proton acceptor (d) is selected from ammonia claim 1 , organic amines claim 1 , organic ammonium hydroxides claim 1 , NHOH claim 1 , and nitrogen containing aromatic heterocycles.11. The process according to claim 1 , wherein the proton acceptor (d) is selected from organic amines NRRR claim 1 , NHOH ...

PROCESS FOR PRODUCING AN AMINOPROPYNE OR ENAMINONE

There is provided a process for producing an aminopropyne or an enaminone comprising the step of reacting a metal acetylide, an amine and a carbonyl-containing compound in the presence of a transition metal catalyst. There is also provided a process for producing an aminopropyne comprising the step of reacting a metal acetylide, an amine and a halide-containing compound in the presence of a transition metal catalyst at a reaction temperature of 50° C. to 150° C. There are also provided processes to further synthesize the aminopropyne produced to obtain a butyneamine, another aminopropyne or a triazol. 1. A process for producing an aminopropyne comprising the step of reacting a metal acetylide , an amine and a halide-containing compound in the presence of a transition metal catalyst at a reaction temperature of 50° C. to 150° C.2. The process as claimed in claim 1 , wherein said halide-containing compound is C-haloalkane. This application is a divisional application of and claims the benefit of priority to U.S. patent application Ser. No. 14/131,083, filed on Jan. 6, 2014, which is a U.S. national stage application under 35 U.S.C. §371 of PCT/SG2012/000240, filed Jul. 6, 2012, and published as WO 2013/006143 A1 on Jan. 10, 2013, which claims priority to Singapore Application No. 201104950-9, filed Jul. 6, 2011, which applications and publication are incorporated by reference as if reproduced herein and made a part hereof in their entirety, and the benefit of priority of each of which is claimed herein.The present invention generally relates to a three component coupling reaction to produce aminopropynes. The present invention also relates to a three component coupling reaction to produce enaminones.Proparglyamines are frequent skeletons and synthetically-versatile key intermediates for the preparation of many nitrogen-containing biologically active compounds. In recent years, the most useful methods for synthesis of aminopropynes include using very sensitive Grignard ...

Cycloalkyl Amine Compounds

Cycloalkyl amine compounds of Formula (I), 2. The compound of claim 1 , wherein Rand Rare both H claim 1 , and R claim 1 , R claim 1 , Rand Rare all H.3. (canceled)5. The compound of claim 4 , wherein Ris H.7. (canceled)9. The compound of claim 1 , wherein ring A is unsubstituted.10. The compound of claim 1 , wherein ring A is substituted with one or more C-Calkyl.11. The compound of claim 10 , wherein ring A is substituted with one C-Calkyl.12. The compound of claim 1 , wherein ring A is optionally substituted C-Ccycloalkyl.13. The compound of claim 12 , wherein the compound is of Formula (Ia) or (Ib) and ring A is unsubstituted cyclobutyl.14. The compound of claim 12 , wherein the compound is of Formula (Ic) and ring A is unsubstituted cyclopentyl.15. The compound of claim 12 , wherein the compound is of Formula (Ic) and ring A is optionally substituted cyclobutyl.16. The compound of claim 2 , wherein each of Rand R claim 2 , independently claim 2 , is H claim 2 , halo claim 2 , or cyano.17. The compound of claim 16 , wherein at least one of Rand Ris halo.18. The compound of claim 17 , wherein each of Rand Ris chloro.19. The compound of claim 16 , wherein Rand R claim 16 , together with the carbon atoms to which they are attached claim 16 , form phenyl claim 16 , pyridyl claim 16 , pyrrolyl claim 16 , furanyl claim 16 , thienyl claim 16 , thiazolyl claim 16 , oxazolyl claim 16 , imidazolyl claim 16 , pyrazolyl claim 16 , isoxazolyl claim 16 , triazolyl claim 16 , oxadiazolyl claim 16 , pyridazinyl claim 16 , pyrazinyl claim 16 , or pyrimidyl.20. The compound of claim 2 , wherein one of Rand Ris H and the other is C-Calkyl optionally substituted with halo or is C-Ccycloalkyl optionally substituted with C-Calkyl.21. The compound of claim 20 , wherein the other of Rand Ris isopropyl or t-butyl claim 20 , optionally substituted with one or more halo groups.22. The compound of claim 1 , wherein one of Rand Ris C-Calkyl optionally substituted with halo and the other is ...

LINK-PLATE CONNECTION FOR MONOPOLE REINFORCING BARS

Reinforcing bars include load transfer connectors. A link plate includes openings that mate with the load transfer connectors to overlie the splice between reinforcing bars being spliced. A cover plate may be fastened over the link plate. 1. A system for reinforcing a monopole comprising:(a) a first reinforcing bar having a first reinforcing bar opening;(b) a second reinforcing bar having a second reinforcing bar opening;(c) a first load transfer connector configured to be received in the first reinforcing bar opening;(d) a second load transfer connector configured to be received in the second reinforcing bar opening; and(e) a link plate configured to overlay at least a portion of the first reinforcing bar and the second reinforcing bar, the link plate defining a first link plate opening and a second link plate opening, the first reinforcing bar and the second reinforcing bar are disposed to at least partially abut the monopole,', 'the first load transfer connector is configured to be received in the first link plate opening to connect the link plate to the first reinforcing bar,', 'the second load transfer connector is configured to be received in the second link plate opening to connect the link plate to the second reinforcing bar,', 'the first load transfer connector is received in the first reinforcing bar opening and in the first link plate opening through an interference fit, a transition fit, or a running fit,', 'the second load transfer connector is received in the second reinforcing bar opening and in the second link plate opening through an interference fit, a transition fit, or a running fit, and', 'the first load transfer connector and the second load transfer connector are disposed adjacent but do not penetrate the monopole., 'wherein'}2. The system of claim 1 , wherein the first load transfer connector is received in the first reinforcing bar opening through an interference fit.3. The system of claim 1 , wherein the first load transfer connector is ...

COMPOSITIONS AND METHODS FOR INHIBITING RETICULON 4

Disclosed herein, inter alia, are compositions and methods useful for inhibiting reticulon 4 (RTN4). 3. (canceled)4. (canceled)6. (canceled)7. The method of claim 1 , wherein Ris independently halogen claim 1 , —CX claim 1 , —CHX claim 1 , —CHX claim 1 , —OCX claim 1 , —OCHX claim 1 , —OCHX claim 1 , —CN claim 1 , —SH claim 1 , —NH claim 1 , —C(O)OH claim 1 , —C(O)NH claim 1 , —OH claim 1 , substituted or unsubstituted C-Calkyl claim 1 , or substituted or unsubstituted 2 to 8 membered heteroalkyl; substituted or unsubstituted C-Ccycloalkyl claim 1 , substituted or unsubstituted 3 to 8 membered heterocycloalkyl claim 1 , substituted or unsubstituted C-Caryl claim 1 , or substituted or unsubstituted 5 to 12 membered heteroaryl.8. (canceled)9. The method of claim 1 , wherein Ris independently —Cl.10. The method of claim 1 , wherein two adjacent Rsubstituents are joined to form a substituted or unsubstituted cycloalkyl claim 1 , substituted or unsubstituted heterocycloalkyl claim 1 , substituted or unsubstituted aryl claim 1 , or substituted or unsubstituted heteroaryl.11. (canceled)12. The method of claim 1 , wherein two adjacent Rsubstituents are joined to form an unsubstituted C-Ccycloalkyl.13. (canceled)14. The method of claim 1 , wherein Lis a bond.15. The method of claim 1 , wherein Lis —NR— or substituted or unsubstituted heterocycloalkylene comprising a ring nitrogen bonded directly to E.16. The method of claim 1 , wherein Lis —NR—.17. The method of claim 16 , wherein Ris hydrogen claim 16 , substituted or unsubstituted C-Calkyl claim 16 , or substituted or unsubstituted 2 to 6 membered heteroalkyl.18. (canceled)19. The method of claim 16 , wherein Ris hydrogen claim 16 , unsubstituted methyl claim 16 , unsubstituted ethyl claim 16 , unsubstituted hexyl claim 16 , or unsubstituted benzyl.20. The method of claim 16 , wherein Ris hydrogen.21. (canceled)23. (canceled)26. The method of claim 1 , wherein the cancer is colorectal cancer.27. (canceled)28. (canceled)30. ...

Inhibitors of indoleamine 2,3-dioxygenase and methods of their use

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the disclosure.

Synthesis of ZSM-5

A molecular sieve having the framework structure of ZSM-5 is produced using one or more of 1,4-bis(N-pentylpyrrolidinium)butane dications, 1,5-bis(N-pentylpyrrolidinium)pentane dications, and 1,6-bis(N-pentylpyrrolidinium)hexane dications as a structure directing agent. 19.-. (canceled)12. The molecular sieve of claim 11 , wherein X includes aluminum claim 11 , and Y includes silicon and/or germanium.14. (canceled) The present application claims priority to and the benefit of U.S. Provisional Application No. 61/740,917 filed on 21 Dec. 2012, which is hereby incorporated by reference in its entirety.This invention relates to the synthesis of ZSM-5, and to the use of the resultant ZSM-5 as an adsorbent and a catalyst for organic conversion reactions.Crystalline ZS M-5, and its conventional preparation using tetrapropylammonium cations as a structure directing agent, are taught by U.S. Pat. No. 3,702,886 and U.S. Pat. No. Re. 29,948, the entire disclosures of which are incorporated herein by reference. Conventional ZSM-5 has a distinctive X-ray diffraction pattern which distinguishes it from organic conversion reactions.In addition to tetrapropylammonium cations, a large number of other organic nitrogen compounds, including certain diquaternary ammonium compounds, have been shown to direct the synthesis of ZSM-5. For example, U.S. Pat. No. 4,585,638 discloses that the synthesis of ZSM-5 can be directed by the diquaternary cation (alkyl)N(CH)N(alkyl), where the alkyl group is propyl or butyl.According to the present invention, it has now been found that ZSM-5 can be synthesized using certain novel bis(N-pentylpyrrolidinium)-diquat-n cations, where n=4, 5 or 6, as a structure directing agent. The ZSM-5 can be made across a wide range of Si/Al ratios (infinity to 12) and, in some cases, it has been found that novel ultra-small forms of ZSM-5 can be produced.In one aspect, the invention resides in a process for producing a molecular sieve having the framework structure of ...

CAPSAICIN AND TRPV1 MODULATOR COMBINATIONS AND METHODS OF USE THEREOF

Provided herein are combinations of capsaicin and TrpV1 modulators that are useful for treating capsaicin-responsive diseases or disorders. 3. The composition of claim 2 , wherein the capsaicin is present in the composition in an amount of from about 40% (w/v) to about 50% (w/v).5. The composition of any one of - claim 2 , wherein the at least one TrpV1 modulator is a TrpV1 antagonist claim 2 , a TrpV1 competitive agonist claim 2 , or combination thereof.6. The composition of claim 4 , wherein the at least one TrpV1 modulator is a triglyceride or spilanthol.7. The composition of any one of - or claim 4 , wherein the at least one TrpV1 modulator is a fatty acid claim 4 , triglyceride claim 4 , or spilanthol.8. The composition of claim 7 , wherein the fatty acid is a polyunsaturated fatty acid (PUFA).9. The composition of claim 8 , wherein the PUFA is anandamide.10. The composition of claim 7 , wherein the fatty acid is an omega-9 fatty acid.11. The composition of claim 10 , wherein the fatty acid is oleic acid or erucic acid.12. The composition of claim 1 , wherein the at least one additional therapeutic agent is a FAAH receptor inhibitor.13. The composition of claim 1 , wherein the at least one additional therapeutic agent is an SPM.14. The composition of claim 13 , wherein the SPM is maresin.15. The composition of any one of - claim 13 , wherein the composition is in a form for oral dosing or administration.16. The composition of any one of - claim 13 , wherein the compound of Formula (I) claim 13 , or an isotopic variant thereof; or a metabolite claim 13 , pharmaceutically acceptable salt claim 13 , solvate claim 13 , or hydrate thereof is present in the composition in an amount of greater than about 10% (w/v).17. The composition of any one of - claim 13 , wherein the compound of Formula (I) claim 13 , or an isotopic variant thereof; or a metabolite claim 13 , pharmaceutically acceptable salt claim 13 , solvate claim 13 , or hydrate thereof is present in the ...

AN IMPROVED PROCESS FOR THE PREPARATION OF VORTIOXETINE AND SALTS THEREOF

The present invention relates to a novel crystalline polymorphic form of 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine hydrochloride; commonly known as vortioxetine hydrochloride (hereafter referred to as the compound (Ia) and process for its preparation comprising of treating the compound (Ia) (as described herein) with a ketone solvent or mixture of ketone solvent with other solvents. The present invention also relates to an improved process for the preparation of vortioxetine hydrobromide (Ia), comprising reacting the compound (I) (as described herein) with hydrogen bromide solution in acetic acid. 1) An improved process for the preparation of vortioxetine hydrobromide (Ia) , comprising:a) optionally dissolving the vortioxetine (I) in an organic solvent; and/orb) treating the resulting solution with hydrogen bromide solution in acetic acid.2) The process as claimed in claim 1 , wherein solvent used in step (a) is selected from ketones such as methyl ethyl ketone claim 1 , acetone claim 1 , methyl isobutyl ketone (MIBK): aprotic solvents such as acetonitrile and proprionitrile; aromatic solvent such as toluene claim 1 , xylene and benzene.3) Crystalline vortioxetine hydrochloride Form-P characterized by an x-ray diffraction pattern (XRD) as shown in4) Crystalline vorioxetine hydrochloride Form-P as claimed in claim 3 , having characteristic X-ray powder diffraction with peaks at about 3.82 claim 3 , 7.66 claim 3 , 11.48 claim 3 , 19.20 claim 3 , 20.23 and 23.1±0 2 degrees two-theta.5) Crystalline vortioxetine hydrochloride Form-P as claimed in claim 3 , having characteristic X-ray powder diffraction pattern with reflections corresponding to the d-spacing values 23.10 claim 3 , 11.53 claim 3 , 7.70 claim 3 , 4.62 claim 3 , 4.39 and 3.85.6) A process for the preparation of vortioxetine hydrochloride (Ia) crystalline Form-P claim 3 , comprises the steps of:a) suspending the vortioxetine hydrochloride (Ia) in a ketone solvent or mixture of ketone solvent with ...

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are neuroactive steroids of the Formula (I): 2. The compound of claim 1 , wherein Ris substituted or unsubstituted Calkyl (e.g. claim 1 , haloalkyl).3. The compound of any one of the preceding claims claim 1 , wherein Ris methyl or CF.4. The compound of any one of the preceding claims claim 1 , wherein Ris methyl.5. The compound of any one of the preceding claims claim 1 , wherein Ris hydrogen.6. The compound of any one of the preceding claims claim 1 , wherein Ris methyl and Ris hydrogen.7. The compound of any one of the preceding claims claim 1 , wherein represents a single bond.11. The compound of any one of the preceding claims claim 1 , wherein A is heterocyclyl or heteroaryl (e.g. claim 1 , nitrogen-containing heterocyclyl or a nitrogen-containing heteroaryl).12. The compound of any one of the preceding claims claim 1 , wherein A is monocyclic or bicyclic.13. The compound of any one of the preceding claims claim 1 , wherein A is substituted with at least one R claim 1 , wherein Ris Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccarbocyclyl claim 1 , Chaloalkyl claim 1 , halogen claim 1 , cyano claim 1 , —OR claim 1 , —C(═O)OR claim 1 , —SR claim 1 , —S(═O)R claim 1 , or S(═O)R claim 1 , wherein Ris hydrogen or Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccarbocyclyl claim 1 , or Chaloalkyl claim 1 , and Ris Calkyl or Ccarbocyclyl.14. The compound of claim 13 , wherein Ris Calkyl claim 13 , halogen claim 13 , or cyano.15. The compound of any one of - claim 13 , wherein A is substituted with 1-3 instances of R.17. The compound of claim 16 , wherein Ris substituted or unsubstituted Calkyl (e.g. claim 16 , haloalkyl).18. The compound of any one of - claim 16 , wherein Ris methyl or CF.19. The compound of any one of - claim 16 , wherein Ris methyl.20. The compound of any one of - claim 16 , wherein Ris hydrogen.21. The compound of any one of - claim 16 , wherein Ris methyl and Ris hydrogen.22. The compound of any one of - claim ...

AMINE CATIONIC LIPIDS AND USES THEREOF

The present invention relates to lipid compounds and uses thereof. In particular, the compounds include a class of cationic lipids having an amine moiety, such as an amino-amine or an amino-amide moiety. The lipid compounds are useful for in vivo or in vitro delivery of one or more agents (e.g., a polyanionic payload or an antisense payload, such as an RNAi agent). 24.-. (canceled)5. The compound of claim 1 , wherein each Rand Ris Calkenyl.6. The compound of claim 1 , wherein Ris Calkyl.7. A formulation comprising a compound of claim 1 , the formulation further comprising a cationic lipid claim 1 , a neutral lipid claim 1 , a sterol derivative and a dsRNA.8. The formulation of claim 7 , wherein the cationic lipid is selected from the group consisting of N claim 7 ,N-dimethyl-(2 claim 7 ,3-dioleyloxy) propylamine (DODMA) claim 7 , 1 claim 7 ,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) claim 7 , 1 claim 7 ,2-dipalmitoyl-sn-glycero-O-ethyl-3-phosphocholine (DPePC) claim 7 , 1 claim 7 ,2-dioleoyl-3-dimethylammonium propane (DODAP) claim 7 , and 1 claim 7 ,2-dioleoyl-3-trimethylammonium-propane (DOTAP); and the neutral lipid is selected from the group consisting of 1 claim 7 ,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) claim 7 , 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) claim 7 , 1 claim 7 ,2-dioleoyl-glycero-sn-3-phosphoethanolamine (DOPE) claim 7 , and sphingomyelin (SM).9. The formulation of claim 7 , wherein the cationic lipid is DODMA and the neutral lipid is DSPC.10. The formulation of claim 7 , wherein the formulation further comprises a PEG-lipid conjugate.11. The formulation of claim 10 , wherein the PEG-lipid conjugate is selected from the group consisting of 1 claim 10 ,2-dimyristoyl-sn-glycerol-3-(methoxy-polyethylene glycol) (PEG-DMG) claim 10 , 1 claim 10 ,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(carbonyl-methoxy-polyethylene glycol) (PEG-DMPE) claim 10 , 1 claim 10 ,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-( ...

DRUG FOR TREATING TUMOR DISEASES AND HAVING ANTIBACTERIAL ANTIVIRUS ANTI-INFLAMMATORY EFFECTS

The present disclosure describes an anti-cancer drug for treating tumor diseases and providing antibacterial, antivirus, and anti-inflammatory effects. The drug contains a naphthalene dicarboxamide compound with a structural formula as shown in Formula I or a biologically acceptable salt or ester form of the compound with the formula I as an active ingredient. The drug is able to help inhibit the growth of tumor cells and possesses certain antibacterial, antivirus, and anti-inflammatory effects. 2. The compound of Claim 1 , wherein the X can be carbonyl Claim 1 , thiocarbonyl Claim 1 , or sulfonyl group; Y can be carbonyl Claim 1 , thiocarbonyl Claim 1 , or sulfonyl group.3. The compound of Claim 1 , wherein X substituents are in the P position of the naphthalene ring and N substituents (connected to Y Claim 1 , shown in the formula) are in the non-substituted para-position of the naphthalene ring.4. The compound of Claim 1 , wherein R Claim 1 , Rand nitrogen atoms connected to them can form a pyrrole ring Claim 1 , tetrahydropyrrole ring Claim 1 , pyridine ring Claim 1 , tetrahydropyridine ring Claim 1 , piperidine ring Claim 1 , piperazine ring Claim 1 , oxazine ring Claim 1 , tetrahydroxazine ring Claim 1 , and morpholine ring; and when R Claim 1 , Rand annular atoms connected to them form a substituted ring structure with 3-8 ring atoms Claim 1 , the formed ring structure should be 4-methyl-piperazinyl or N-morpholinyl; or Rand Rare selected independently from hydrogen Claim 1 , Calkyl Claim 1 , Calkoxy Claim 1 , cyclopropane Claim 1 , cyclohexane Claim 1 , Calkoxycarbonyl Claim 1 , Calkylcarbonyl Claim 1 , aminocarbonyl Claim 1 , Calkylaminocarbonyl Claim 1 , nitro Claim 1 , oxazolyl Claim 1 , thiazolyl Claim 1 , pyridyl Claim 1 , dihydropyridyl Claim 1 , tetrahydropyridyl Claim 1 , piperidinyl Claim 1 , thiazinyl Claim 1 , pyrrolyl Claim 1 , imidazolyl Claim 1 , pyrazolyl Claim 1 , pyrimidinyl Claim 1 , piperazinyl Claim 1 , morpholinyl Claim 1 , furanyl Claim ...

SYNTHESIS OF DEUTERATED MORPHOLINE DERIVATIVES

The present invention is directed to a process for preparing a 2,26,6-d-morpholine derivative represented by Structural Formula (I): 110.-. (canceled)12. The compound of claim 11 , wherein the deuterium enrichment at each position designated as deuterium is at least about 85%.13. The compound of claim 12 , wherein R claim 12 , R claim 12 , Rand R are each —H; Ris benzyl; and the deuterium enrichment at each position designated as deuterium is 95%.15. The compound of claim 14 , wherein each of R claim 14 , R claim 14 , Rand R is hydrogen claim 14 , or a salt thereof; and wherein the deuterium enrichment at each position designated as deuterium is at least about 95%.16. The compound of claim 14 , wherein Ris benzyl claim 14 , —SO-aryl claim 14 , or —SO-heteroaryl.17. The compound of claim 15 , wherein Ris benzyl.18. The compound of claim 14 , wherein Ris alkyl optionally substituted with one or more groups selected from halogen claim 14 , Calkyl claim 14 , —NO claim 14 , —CN claim 14 , —NH claim 14 , —NHR claim 14 , —N(R) claim 14 , —C(═O)NRR claim 14 , and —SONRR claim 14 , wherein each Calkyl substituent is optionally substituted with one or more groups selected from halogen claim 14 , Calkyl claim 14 , Calkoxy claim 14 , —OH claim 14 , Chaloalkyl and Chaloalkoxy.20. A pyrogen-free pharmaceutical composition comprising the compound of ; and a pharmaceutically acceptable carrier.21. A composition comprising the compound of ; and a pharmaceutically acceptable carrier for use in treating a bacterial infection or a fungal disorder in a subject in need thereof.22Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyrogenes, Enterococcus faecalis, Staphylococcus epidermidis, Staphyloccocus haemolyticusPasteurella multocida.. The composition of claim 21 , wherein the bacterial infection is caused by a bacteria selected from claim 21 , and23Enterococcus faeciumStaphylococcus aureusStreptococcus ...

METHOD OF INHIBITING APOLIPOPROTEIN-E EXPRESSION WHILE INCREASING EXPRESSION OF AT LEAST ONE OF LDL-RECEPTOR PROTEIN OR ABCA1 PROTEIN COMPRISING ADMINISTERING A SMALL COMPOUND

This invention offers an effective method of decreasing expression of apolipoprotein E and increasing expression of at least one of either LDL-receptor protein or AbcA1 protein including selecting mammalian cells expressing apoE and at least one of either LDL-receptor protein or AbcA1 protein, contacting the mammalian cell with an effective amount of a compound having general formula (I) or general formula (II) in an amount sufficient to decrease expression of the apoE and increase expression of at least one of the LDL-receptor protein or the AbcA1 protein in the mammalian cell. 3. A method according to claim 1 , wherein said selecting step selects for mammalian cells expressing apolipoprotein E claim 1 , LDL-receptor protein claim 1 , and AbcA1 protein claim 1 , and wherein said method decreases apolipoprotein E and increases expression of both said LDL-receptor protein and said AbcA1 protein.4. A method according to claim 2 , wherein said selecting step selects for mammalian cells expressing apolipoprotein E claim 2 , LDL-receptor protein claim 2 , and AbcA1 protein claim 2 , and wherein said method decreases apolipoprotein E and increases expression of both said LDL-receptor protein and said AbcA1 protein.5. A method according to claim 1 , wherein said effective amount is 10 μM.6. A method according to claim 2 , wherein said effective amount is 10 μM. Alzheimer's Disease is a common form of dementia associated with memory loss, intellectual function decline, depression, and disorientation. Alzheimer's Disease affects more than 5 million people in the United States and costs over $200 billion every year. (Alzheimer's Association, (2012) 8: 131-168.) It is found in 13% of the population over the age of 65 and 45% of the population over the age of 85. (Alzheimer's Association, (2012) 8: 131-168.) With a rapidly aging American population, prevalence of Alzheimer's Disease is expected to increase 2.5-fold to 13 million people in the United States in the next few ...

Salts of fenofibric acid and pharmaceutical formulations thereof

In one aspect, the present invention relates to a formulation in the form of molecular dispersion comprising i) fenofibric acid, a physiologically acceptable salt or derivative thereof and optionally other active substances, ii) a binder component comprising at least one enteric binder, and optionally iii) other physiologically acceptable excipients. In a second aspect, the present invention relates to novel salts of fenofibric acid that are photostable when compared to other salts of fenofibric acid.

PRODUCTION METHOD FOR 2-ALKENYLAMINE COMPOUND

Provided is a method for producing a 2-alkenylamine compound efficiently and at low cost, using a primary or secondary amine compound and a 2-alkenyl compound as the starting materials therefor. The 2-alkenyleamine compound is produced by 2-alkenylating a primary or secondary amine compound, using a specified 2-alkenylating agent and in the presence of a catalyst comprising a complexing agent and a transition metal precursor stabilized by a monovalent anionic five-membered conjugated diene. 3. The method for producing a 2-alkenylamine compound according to claim 1 , wherein the transition metal precursor comprises at least one of transition metal atoms selected from the group consisting of the transition metals belonging to Group 8 and Group 9 of the periodic table.4. The method for producing a 2-alkenylamine compound according to claim 3 , wherein the transition metal atom is selected from the group consisting of ruthenium claim 3 , rhodium claim 3 , and iridium.6. The method for producing a 2-alkenylamine compound according to claim 1 , wherein all of R claim 1 , R claim 1 , R claim 1 , Rand Rin formula (1) each are a hydrogen atom.7. The method for producing a 2-alkenylamine compound according to claim 1 , wherein the primary or secondary amine compound is selected from the group consisting of a saturated C1 to C30 aliphatic amine having one or two amino group(s) in the molecule claim 1 , a saturated C3 to C30 alicyclic amine having one or two amino group(s) in the molecule claim 1 , a C6 to C30 arylamine compound having 1 to 10 amino group(s) in the molecule claim 1 , and a nitrogen-containing C2 to C30 heterocyclic compound having a hydrogen atom on the nitrogen atom constituting the heterocyclic ring.8. The method for producing a 2-alkenylamine compound according to claim 1 , wherein 0.000001 to 10 moles of the transition metal complex is used relative to one total mole of the primary or secondary amine compound and the 2-alkenyl compound (moles of the primary ...

METHOD FOR PRODUCING AROMATIC COMPOUND

In a cross coupling reaction, in a case where a halogen atom is selected as the leaving group of the raw material compound, a harmful halogen waste forms as a by-product after the reaction, and disposal of the waste liquid is complicated and environmental burden is high. In a carbon-hydrogen activation cross coupling reaction which requires no halogen atom as the leaving group, although no halogen waste forms as a by-product, the reaction substrate is considerably restricted, and the reaction remains a limited molecular construction method. 1. A method for producing an aromatic compound , which comprises subjecting an aromatic nitro compound and a boronic acid compound to a cross coupling reaction in the presence of a metal catalyst.2. The production method according to claim 1 , wherein the boronic acid compound is an aromatic boronic acid compound claim 1 , and the reaction product is a linked aromatic compound.3. The production method according to claim 1 , wherein the metal catalyst is a transition metal catalyst.4. The production method according to claim 3 , wherein the transition metal catalyst is a palladium or nickel compound.5. The production method according to claim 1 , wherein a phosphine compound coexists. The present invention relates to a method for producing an aromatic compound. More specifically, it relates to a method for producing an aromatic compound, which comprises conducting a cross coupling reaction using an aromatic nitro compound and a boronic acid compound as raw materials.A multisubstituted aromatic compound is widely used in a pharmaceutical and agrochemical field, a natural product synthesis field, a liquid crystal and organic electroluminescence field, etc., and as a method for constructing its molecular skeleton, various means have been developed. Among them, a reaction for synthesizing a linked aromatic compound using an aromatic boronic acid derivative (Suzuki cross coupling reaction) is one of particularly useful means, and ...

Phenyl-Piperazine Derivatives As Serotonin Reuptake Inhibitors

The invention provides compounds represented by the general formula I 2. The compound according to claim 1 , provided that the compound is not 1-(2-phenoxyphenyl)piperazine.3. The compound according to claim 1 , provided that the compound is not 1-[2-(2-Methoxyphenoxy)phenyl]piperazine claim 1 , 1-[2-(2 claim 1 ,6-dimethoxyphenoxy)phenyl]-[1 claim 1 ,4]-diazepane claim 1 , 1-{2-[3-(dimethylamino)phenoxy]phenyl}piperazine claim 1 , 1-[2-(4-methylphenoxy)phenyl]piperazine claim 1 , 1-[2-(3-methylphenoxy)phenyl]piperazine claim 1 , 1-[2-(3-chlorophenoxy)phenyl]piperazine claim 1 , 1-[2-(3-methoxyphenoxy)phenyl]piperazine and 1-(2-phenoxyphenyl)-piperazine.4. The compound according to claim 1 , wherein p is 0 claim 1 , 1 or 2.5. The compound according to claim 1 , wherein Ris C-alkyl.6. The compound according to claim 1 , wherein m is 1 or 2.7. The compound according to claim 1 , wherein q is 0 claim 1 , 1 or 2.8. The compound according to claim 1 , wherein Ris trifluoromethyl claim 1 , or C-alkyl.9. The compound according to claim 1 , wherein s is 1 or 2.10. The compound according to claim 1 , wherein Ris selected from the group consisting of halogen claim 1 , C-alkoxy claim 1 , C-sulfanyl claim 1 , C-alkyl claim 1 , hydroxy or trifluoromethyl.11. The compound according to claim 1 , said compound being1-[2-(2-Trifluoromethylphenylsulfanyl)phenyl]piperazine,1-[2-(4-Bromophenylsulfanyl)phenyl]piperazine,1-{2-[4-(Methylsulfanyl)phenylsulfanyl]phenyl}piperazine,1-[2-(4-Hydroxyphenylsulfanyl]phenyl}piperazine,1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(3,5-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(2,6-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(2,5-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(2-Trifluoromethylphenylsulfanyl)phenyl][1,4]diazepane,1-[2-(3-Methylphenylsulfanyl)phenyl]-[1,4]-diazepane,1-[2-(4-Butylphenoxy)phenyl]piperazine,1-[2-(4-Methoxyphenoxy)phenyl]piperazine,2-(4-Methylphenylsulfanyl)phenyl-1-piperazine,1-[2-(4-Chlorophenylsulfanyl) ...

PROCESS FOR PREPARING AROMATIC AND HETEROAROMATIC AMINES

A process is described for preparing aromatic and heteroaromatic amines of the general formula (I) Ar—NRR, in which an aromatic compound with the general formula (II) Ar—X is reacted in the presence of a catalyst with an amine of the general formula (III) H—NRRand a base, wherein the catalyst is selected from transition metal complexes having one or more ligands with the general formula (IV). 2. The process as claimed in claim 1 , wherein Y is Cl claim 1 , Br or —OR claim 1 , where Ris i-propyl or tert-butyl.3. The process as claimed in claim 1 , wherein Rand Rand/or Rand Rare i-propyl or tert-butyl.4. The process as claimed in claim 1 , wherein the base is selected from among alkali metal hydroxides claim 1 , alkali metal alkoxides claim 1 , alkali metal carbonates claim 1 , alkali metal phosphates claim 1 , ammonia claim 1 , C-C-alkylamine claim 1 , di(C-C-alkyl)amine claim 1 , benzylamine claim 1 , piperidine and morpholine.5. The process as claimed in claim 1 , wherein the transition metal is selected from among iron claim 1 , palladium claim 1 , nickel claim 1 , cobalt claim 1 , platinum claim 1 , rhodium and ruthenium.6. The process as claimed in claim 5 , wherein the transition metal complex is prepared from transition metal compounds selected from among Pd(OAc) claim 5 , Pd(acac) claim 5 , (allPdCl) claim 5 , PdCl claim 5 , Pd(dba)and Pd(dba). The present invention relates to a process for preparing aromatic and heteroaromatic amines from the corresponding aryl and heteroaryl halides or sulfonates in the presence of a catalyst and a base.Aromatic and heteroaromatic amines are of great industrial interest. The preparation of these compounds by catalytic amination of the corresponding chlorine, bromine or iodine compounds to form arylamines is a conversion important in organic synthesis (B. Schlummer, U. Scholz, 2004, 346, 1599). In general, the reaction requires both a base for binding the liberated acid HX (X=Cl, Br or I) and a transition metal catalyst. ...

NOVEL COMPOUNDS ADVANTAGEOUS IN THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS

A series of novel amides showing broad pharmaceutical activity. Compounds described herein are effective as anticonvulsants, chemical countermeasures, and analgesics. Such compounds also show, neuroprotective/neuroreparative effects and activity against spinal muscular atrophy. Such pharmaceutically active compounds show utility in the treatment of central nervous system (“CNS”) diseases and disorders, such as anxiety, depression, insomnia, migraine headaches, schizophrenia, neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's, ALS, and Huntington's disease) spasticity, and bipolar disorder. Furthermore, such compounds may additionally find utility as analgesics (e.g., for the treatment of chronic or neuropathic pain) and as neuroprotective agents useful in the treatment of stroke(s), and/or traumatic brain and/or spinal cord injuries. 2. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of at least one compound of Formula I of admixed with at least one of a pharmaceutically acceptable carrier or an excipient.3. The pharmaceutical composition as in claim 2 , wherein the excipient includes a carrier.4. A pharmaceutical composition for treating and/or preventing one or more neurodegenerative disease claim 1 , comprising a neuroprotective and/or neuroreparative effective amount of at least one compound of Formula I of admixed with at least one of a pharmaceutically acceptable carrier or an excipient.5. The pharmaceutical composition of claim 4 , wherein the neurodegenerative disease is at least one of Huntington's Disease claim 4 , Parkinson's Disease claim 4 , Alzheimer's Disease claim 4 , or amyotrophic lateral sclerosis (ALS).6. A pharmaceutical composition for treating and/or preventing spinal muscular atrophy claim 1 , comprising a therapeutically effective amount of at least one compound of Formula I of admixed with at least one of a pharmaceutically acceptable carrier or an excipient.7. A method for treating and/ ...

Phenyl-Piperazine Derivatives As Serotonin Reuptake Inhibitors

The invention provides compounds represented by the general formula I 115-. (canceled)17. The process of claim 16 , wherein each Ris independently C-alkyl.18. The process of claim 16 , wherein the compound of formula Ia is 1-[2-(2 claim 16 ,4-dimethylphenylsulfanyl)phenyl]piperazine.19. 1-[2-(2 claim 16 ,4-Dimethylphenylsulfanyl)phenyl]piperazine or an acid addition salt thereof obtained in the process of .21. The process of claim 20 , wherein each Ris independently C-alkyl.22. The process of claim 20 , wherein the compound of formula Ia is 1-[2-(2 claim 20 ,4-dimethylphenylsulfanyl)phenyl]piperazine.23. 1-[2-(2 claim 20 ,4-Dimethylphenylsulfanyl)phenyl]piperazine or an acid addition salt thereof obtained in the process of .25. The process of claim 24 , wherein each Ris independently C-alkyl.26. The process of claim 24 , wherein the compound of formula Ia is 1-[2-(2 claim 24 ,4-dimethylphenylsulfanyl)phenyl]piperazine.27. 1-[2-(2 claim 24 ,4-Dimethylphenylsulfanyl)phenyl]piperazine or an acid addition salt thereof obtained in the process of . The present invention relates to novel compounds which are serotonin reuptake inhibitors and as such effective in the treatment of for example depression and anxiety.Selective serotonin reuptake inhibitors (hereinafter referred to as SSRIs) have become first choice therapeutics in the treatment of depression, certain forms of anxiety and social phobias, because they are effective, well tolerated and have a favourable safety profile compared to the classic tricyclic antidepressants.However, clinical studies on depression indicate that non-response to SSRIs is substantial, up to 30%. Another, often neglected, factor in antidepressant treatment is compliance, which has a rather profound effect on the patient's motivation to continue pharmacotherapy.First of all, there is the delay in therapeutic effect of SSRIs. Sometimes symptoms even worsen during the first weeks of treatment. Secondly, sexual dysfunction is a side effect common ...

Amine Cationic Lipids and Uses Thereof

The present invention relates to lipid compounds and uses thereof. In particular, the compounds include a class of cationic lipids having an amine moiety, such as an amino-amine or an amino-amide moiety. The lipid compounds are useful for in vivo or in vitro delivery of one or more agents (e.g., a polyanionic payload or an antisense payload, such as an RNAi agent). 5. The compound of claim 1 , wherein each Rand Ris claim 1 , independently claim 1 , substituted Calkyl claim 1 , substituted Calkenyl claim 1 , substituted Calkynyl claim 1 , substituted Cheteroalkyl claim 1 , substituted Cheteroalkenyl claim 1 , or substituted Cheteroalkynyl.6. The compound of claim 1 , wherein Ris substituted Calkyl or substituted heterocyclyl.7. A formulation comprising a compound of claim 1 , the formulation further comprising a cationic lipid claim 1 , a neutral lipid claim 1 , a sterol derivative and a dsRNA.8. The formulation of claim 7 , wherein the cationic lipid is selected from the group consisting of N claim 7 ,N-dimethyl-(2 claim 7 ,3-dioleyloxy) propylamine (DODMA) claim 7 , 1 claim 7 ,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) claim 7 , 1 claim 7 ,2-dipalmitoyl-sn-glycero-O-ethyl-3-phosphocholine (DPePC) claim 7 , 1 claim 7 ,2-dioleoyl-3-dimethylammonium propane (DODAP) claim 7 , and 1 claim 7 ,2-dioleoyl-3-trimethylammonium-propane (DOTAP); and the neutral lipid is selected from the group consisting of 1 claim 7 ,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) claim 7 , 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) claim 7 , 1 claim 7 ,2-dioleoyl-glycero-sn-3-phosphoethanolamine (DOPE) claim 7 , and sphingomyelin (SM).9. The formulation of claim 7 , wherein the cationic lipid is DODMA and the neutral lipid is DSPC.10. The formulation of claim 7 , wherein the formulation further comprises a PEG-lipid conjugate.11. The formulation of claim 10 , wherein the PEG-lipid conjugate is selected from the group consisting of 1 claim 10 ,2-dimyristoyl-sn- ...

LIPID MEMBRANE STRUCTURE FOR DELIVERY INTO siRNA CELL

A lipid membrane structure includes, as lipid components, a lipid compound represented by Formula (I): 1. A lipid compound represented by Formula (I) or a salt thereof ,{'br': None, 'sup': 1', '2, 'sub': 2', 'a', 'b, '(R)(R)C(OH)—(CH)—(O—CO)—X\u2003\u2003(I)'}{'sup': 1', '2, 'claim-text': {'br': None, 'sub': 3', '2', 'q', 'r', '2', 's', 't', '2', 'u', 'c', '2', 'v, 'CH—(CH)—(CH═CH)—(CH)—(CH═CH)—(CH)—(CO—O)—(CH)—\u2003\u2003(A)'}, '[in the formula, a represents an integer of 3 to 5; b represents an integer of 0 or 1; and Rand Reach independently represents a group represented by Formula (A){'sub': b', '1-4', '2-4, 'claim-text': {'br': None, 'sub': '2', 'i': 'd', 'sup': 3', '4, '—(CH)-N(R)(R)\u2003\u2003(B)'}, '(in the formula, q represents an integer of 1 to 9; r represents 0 or 1; s represents an integer of 1 to 3; t represents 0 or 1; u represents an integer of 1 to 8; c represents 0 or 1; and v represents an integer of 4 to 12, where, a case in which q is an integer of 3 to 5, r and t are 1, s is 1, and u+v is an integer of 6 to 10 is excluded in a case where both b and c are 0); and X represents a 5- to 7-membered non-aromatic heterocyclic group (where, the group is bonded to (O—CO)— by a carbon atom, and one or two Calkyl groups or Calkenyl groups may be substituted on the ring), or X represents a group represented by Formula (B){'sup': 3', '4', '3', '4, 'sub': 1-4', '2-4', '1-4', '2-4', '1-4', '2-4, '(in the formula, d represents an integer of 0 to 3, and Rand Reach independently represents a Calkyl group or a Calkenyl group (where, the Calkyl group or Calkenyl group may be substituted by one or two phenyl groups), but Rand Rmay be bonded to each other to form a 5- to 7-membered non-aromatic heterocycle (where, one or two Calkyl groups or Calkenyl groups may be substituted on the ring)].'}2. The lipid compound or a salt thereof according to claim 1 , wherein r and t are 0 claim 1 , and q+s+u is an integer of 8 to 18 and is preferably an integer of 10 to 16.3. ...

Triaryl phosphine ligands, preparation method therefor, and use in catalysing coupling reactionsons

Triaryl phosphine ligands, as shown in general formulae Ia and Ib, or a mixture thereof, and a preparation method therefor. The invention addresses the deficiencies of biaryl phosphine ligands invented by Buchwald et al. Also provided are a triaryl phosphine coordinated palladium complex, a system composed of triaryl phosphine ligand and a palladium salt or complex, and a use of the triaryl phosphine coordinated palladium complex in catalysing organic reactions, in particular a use in catalysis of coupling reactions involving (pseudo)halogenated aromatic hydrocarbon as substrate.

Enantiomerically pure adamantane carboxamides for the treatment of filovirus infection

The compounds of the invention as shown by general structure I, as shown below, are effective in treating filovirus infections.X is selected from the group consisting of O and H;R1 is selected from (C6 to C10) aryl and (C2 to C9) heteroaryl, andR2 is selected from (C1 to C10) alkyl, (C1 to C10) alkenyl, (C1 to C10) alkynyl, (C3 to C10) cycloalkyl, and (C5 to C10) cycloalkenyl, andNR3aR3b is defined in the specification.These compounds are effective in treating filovirii infections including Ebolavirus and Marburg virus.

REACTIVE IONIC LIQUIDS

The invention relates to reactive ionic liquids containing organic cations with groups or substituents which are susceptible to electrochemical reduction and anions obtained from fluoroalkyl phosphates, fluoroalkyl phosphinates, fluoroalkyl phosphonates, acetates, triflates, imides, methides, borates, phosphates and/or aluminates, for use in electrochemical cells, such as lithium ion batteries and double-layer capacitors. 3. Electrolyte comprising at least one conductive salt claim 1 , an aprotic solvent or solvent mixture claim 1 , at least one ionic liquid according to and optionally further additives.4. Electrolyte according to claim 3 , characterised in that the conductive salt is a lithium conductive salt claim 3 , such as LiPF claim 3 , LiN(SOCF) claim 3 , LiN(SOCF) claim 3 , LiFP(CF) claim 3 , LiFP(CF) claim 3 , LiB(CO)or LiFB(CO4).5. Electrolyte according to claim 3 , characterised in that the conductive salt is selected from the following compounds: N(CH)BF claim 3 , N(CH)PF claim 3 , N(CH)(CH)BF claim 3 , N(CH)(CH)PF claim 3 , N(CH)N(SOCF) claim 3 , N(CH)(CH)N(SOCF) claim 3 , N(CH)FP(CF) claim 3 , N(CH)(CH)FP(CF).6. Electrolyte according to claim 3 , characterised in that the aprotic solvent consists of organic open-chain or cyclic carbonates claim 3 , carboxylic acid esters claim 3 , nitrites claim 3 , ethers claim 3 , lactones or a mixture thereof.7. Process for the preparation of ionic liquids of the formula I according to claim 1 , comprising the following steps:{'sup': '+', 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'Preparation of heterocyclic cations K having alkyl-, carboxylate-, carbonate- or cyano-containing side chains according to as onium chlorides or bromides from the corresponding amines, phosphines, halocarboxylates, halocarbonates, haloalkyl nitriles or alkyl halides by conventional wet-chemical methods'}Reaction of these cationic onium chlorides or bromides the corresponding anionic potassium and/or, sodium fluoroalkylphosphates and ...

PHOSPHINE LIGANDS FOR CATALYTIC REACTIONS

The disclosure is directed to: (a) phosphacycle ligands; (b) catalyst compositions comprising phosphacycle ligands; and (c) methods of using such phosphacycle ligands and catalyst compositions in bond forming reactions. 130-. (canceled)33. The method of claim 31 , wherein X is attached to an atom of Aradjacent to the atom bonded to Ar.35. The method of claim 34 , wherein Rand Rare hydrogen.36. The method of claim 34 , wherein Rand Rtogether with the carbon atom to which they are attached form a 3- claim 34 , 4- claim 34 , 5- claim 34 , 6- claim 34 , or 7-membered spirocyclic ring containing 0 claim 34 , 1 claim 34 , or 2 ring heteroatoms.38. The method of claim 31 , wherein Arand Arare each aryl.39. The method of claim 31 , wherein Aris substituted with two Rand Aris substituted with three R.40. The method of claim 31 , wherein Ris alkyloxy and wherein Ris alkyl.41. The method of claim 31 , wherein Ris isopropyl.43. The method of claim 42 , wherein Rtogether with Rform a 5-membered spiro ring containing two heteroatoms.44. The method of claim 43 , wherein the two heteroatoms are each oxygen.45. The method of claim 31 , wherein R claim 31 , R claim 31 , R claim 31 , and Rare each methyl.48. The method of claim 47 , wherein the compound is selected from the group consisting of:2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphinane;2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphinan-4-one;2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphinan-4-ol;7,7,9,9-tetramethyl-8-(2′,4′,6′-triisopropylbiphenyl-2-yl)-1,4-dioxa-8-phosphaspiro[4.5]decane;8,8,10,10-tetramethyl-9-(2′,4′,6′-triisopropylbiphenyl-2-yl)-1,5-dioxa-9-phosphaspiro[5.5]undecane;3,3,8,8,10,10-hexamethyl-9-(2′,4′,6′-triisopropylbiphenyl-2-yl)-1,5-dioxa-9-phosphaspiro[5.5]undecane;1-(2′-(dimethylamino)-6′-methoxybiphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;1-(2′,6′-bis(dimethylamino)biphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one;1-(2′,6′-dimethoxybiphenyl-2 ...

SILICON-BASED CROSS COUPLING AGENTS AND METHODS OF THEIR USE

Compositions and methods using silicon-based cross-coupling agents in the formation of carbon-carbon and carbon-nitrogen bonds are described. 3. The compound of claim 1 , wherein Y is CH.4. The compound of claim 1 , wherein Y is N.5. The compound of claim 1 , wherein Rand Rare independently methyl claim 1 , ethyl claim 1 , propyl claim 1 , or isopropyl.6. The compound of claim 5 , wherein Rand Rare independently methyl claim 5 , ethyl claim 5 , or isopropyl.7. The compound of claim 5 , wherein Rand Rare each methyl.8. The compound of claim 5 , wherein Rand Rare each isopropyl.9. The compound of claim 5 , wherein Rand Rare each ethyl.10. The compound of claim 1 , wherein Ris Cstraight or branched-chain alkyl optionally substituted with one or more Calkoxy.11. The compound of claim 10 , wherein Ris Cstraight or branched-chain alkyl optionally substituted with one or more Calkoxy.12. The compound of claim 1 , wherein Ris Cstraight or branched-chain alkyl.13. The compound of claim 12 , wherein Ris n-butyl claim 12 , isobutyl claim 12 , or tert-butyl.14. The compound of claim 12 , wherein Ris n-butyl.15. The compound of claim 1 , wherein Ris Cstraight or branched-chain alkyl substituted with one or more halogen.16. The compound of claim 15 , wherein Ris —CF.17. The compound of claim 1 , wherein Ris phenyl optionally substituted with one or more nitro claim 1 , diCalkylamino claim 1 , Calkoxy claim 1 , or Calkyl.18. The compound of claim 17 , wherein Ris phenyl optionally substituted with one or more diCalkylamino claim 17 , Calkoxy claim 17 , or Calkyl.19. The compound of claim 17 , wherein Ris phenyl.20. The compound of claim 1 , wherein Ris pyridyl.21. The compound of claim 1 , wherein Ris a polymer.22. The compound of claim 1 , wherein Ris H.23. The compound of claim 1 , wherein Ris —CF.24. The compound of claim 1 , wherein Ris hydrogen claim 1 , Calkoxy claim 1 , Calkyl claim 1 , or aryl.25. The compound of claim 24 , wherein Ris hydrogen claim 24 , Calkoxy claim 24 ...

COMPOSITE CONTAINING CATALYTIC METAL NANOPARTICLES, AND USE FOR SAME

Provided is a material that, when compared with SAPd, exhibits the similar activity in cross-coupling (CC) reactions, can decrease the amount of catalytic metal that is mixed into the reaction product, and increases the number of times use can be repeated. Provided are a catalyst and a catalyst precursor that use a catalytic metal other than Pd and that exhibit the CC reaction activity similar to when Pd is used. Provided are a catalyst and a catalyst precursor that exhibit the similar CC reaction activity when using Pd or a catalytic metal other than Pd, without using a carrier such as metal and without using piranha solution. A composite wherein catalytic metal nanoparticles are dispersed in a continuous phase comprising a polymer having C2-6 alkylene group units and phenylene group units (an alkylene group unit being bonded to at least the first and fourth position of the phenylene group unit). The particle diameter of the catalytic metal nanoparticles is at most 20 nm. A composite structure including a substrate, and the aforementioned composite provided to the surface of the substrate. A method for manufacturing the composite structure by dehydrocondensating, in the presence of a catalytic metal compound, a benzene compound having at least two alkyl groups (two of the alkyl groups being at the first and fourth position) in order to form the composite on the substrate surface. 117-. (canceled)18. A method for manufacturing a coupling product comprising subjecting a plurality of organic compounds to a coupling reaction to obtain a coupling product with a composite in which catalytic metal nanoparticles are dispersed in a continuous phase comprised of a polymer having a phenylene group unit and an alkylene group unit , the alkylene group having a number of carbon atoms ranging from 2 to 6 , wherein the alkylene group unit is bonded to the phenylene group unit in at least positions 1 and 4 , and wherein at least a portion of the catalytic metal nanoparticles has a ...

SYNTHESIS OF ZEOLITES USING AN ORGANOAMMONIUM COMPOUND

A method for synthesizing a zeolite includes the steps of: (a) preparing an aqueous mixture comprising water, a substituted hydrocarbon and an amine; (b) reacting the aqueous mixture; (c) obtaining a solution comprising an organoammonium product; (d) forming a reaction mixture including reactive sources of M, Al, Si, optionally seeds of a layered material L, and the solution, wherein M is a metal; and (e) heating the reaction mixture to form the zeolite. The substituted hydrocarbon can be an α,ω-dihalogen substituted alkane, and the amine is preferably essentially incapable of undergoing pyramidal inversion. 1. A method for synthesizing a zeolite , the method comprising:(a) preparing an aqueous mixture comprising water, a substituted hydrocarbon and an amine other than trimethylamine wherein the amine is a tertiary amine or secondary amine having 9 or less carbon atoms and being essentially incapable of undergoing pyramidal inversion, or combinations thereof;(b) reacting the aqueous mixture;(c) obtaining a solution comprising an organoammonium product;(d) forming a reaction mixture including reactive sources of M, Al, Si, optionally seeds of a layered material L, and the solution, wherein M is a metal; and(e) heating the reaction mixture to form the zeolite.2. The method of claim 1 , wherein the step of reacting the aqueous mixture occurs at a temperature from about 20° C. to about 100° C.3. The method of claim 1 , wherein the organoammonium product is a structure directing agent.4. The method of wherein the substituted hydrocarbon is selected from the group consisting of halogen substituted alkanes having from 2 to 8 carbon atoms claim 1 , α claim 1 ,ω-dihalogen substituted alkanes having from 3 to 6 carbon atoms claim 1 , di-halogen substituted alkanes having from 3 to 8 carbon atoms claim 1 , tri-halogen substituted alkanes having from 3 to 8 carbons and combinations thereof.5. The method of wherein the substituted hydrocarbon is a halogen substituted alkane ...

INDENE DERIVATIVES, THEIR PREPARATION AND USE AS MEDICAMENTS

The present invention relates to new indene derivatives having a great affinity for sigma receptors, especially sigma-1 receptors, as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments. 115-. (canceled)17. The compound according to claim 16 , wherein R claim 16 , Rand Rare independently selected from hydrogen or Calkyl.21. The compound according to claim 16 , which is selected from the group consisting of:[1] 4-(2-(7-phenyl-1H-inden-3-yl)ethyl)morpholine maleate,[2] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)azepane hydrochloride,[3] 4-(2-(7-(pyridin-4-yl)-1H-inden-3-yl)ethyl)morpholine maleate,[4] 1-(2-(7-(3-fluoropyridin-4-yl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,[5] 1-methyl-4-(2-(7-phenyl-1H-inden-3-yl)ethyl)piperazine maleate,[6] 1-phenyl-4-(2-(7-phenyl-1H-inden-3-yl)ethyl)piperazine maleate,[7] 1-(3-chlorophenyl)-4-(2-(7-phenyl-1H-inden-3-yl)ethyl)piperazine maleate,[8] 1-(2-(7-phenyl-1H-inden-3-yl)ethyl)piperidine maleate,[9] 1-(2-(7-phenyl-1H-inden-3-yl)ethyl)azepane maleate,[10] 4-phenyl-1-(2-(7-phenyl-1H-inden-3-yl)ethyl)piperidine maleate,[11] 4-(2-(2-methyl-7-phenyl-1H-inden-3-yl)ethyl)morpholine maleate,[12] 1-methyl-4-(2-(2-methyl-7-phenyl-1H-inden-3-yl)ethyl)piperazine maleate,[13] 4-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)morpholine maleate,[14] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)-4-phenylpiperazine maleate,[15] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)piperidine maleate,[16] 1-(2-(7-(4-fluorophenyl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,[17] 1-(2-(7-(3-fluorophenyl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,[18] 4-(2-(7-(3-fluorophenyl)-1H-inden-3-yl)ethyl)morpholine maleate,[19] 4-(2-(7-(3,4-dichlorophenyl)-1H-inden-3-yl)ethyl)morpholine maleate,[20] 1-(2-(7-(3,4-dichlorophenyl)-1H-inden-3-yl)ethyl)-4-methylpiperazine maleate,[21] 4-(2-(7-(4-methoxyphenyl)-1H-inden-3-yl)ethyl)morpholine maleate,[22] 1-(2-(7-(4-methoxyphenyl)-1H-inden-3-yl ...

Styrenyl Derivative Compounds for Treating Ophthalmic Diseases and Disorders

The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are styrenyl derivative compounds, including but not limited to stilbene derivative compounds, and compositions comprising these compounds, that are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease. 184.-. (canceled)86. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein Ris cyclohexyl.87. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein R claim 85 , R claim 85 , Rand Rare each independently hydrogen claim 85 , halogen claim 85 , alkyl claim 85 , fluoroalkyl claim 85 , —OR claim 85 , or —NRR claim 85 , wherein each Ris independently hydrogen or alkyl.88. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein R claim 85 , R claim 85 , Rand Rare each the same or different and independently hydrogen claim 85 , halogen claim 85 , —OR claim 85 , or alkyl.89. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , selected from:(E)-3-(3-(2-cyclohexylvinyl)phenyl)propan-1-amine;(E)-1-(3-(3-amino-1-hydroxypropyl)styryl)cyclohexanol;(E)-1-(3-((1R,2R)-3-amino-1-hydroxy-2-methylpropyl)styryl)cyclohexanol;(E)-1-(3-(3-amino-1-hydroxypropyl)-5-fluoro styryl)cyclohexanol;(E)-1-(3-(3-amino-1-hydroxypropyl)-2-fluoro styryl)cyclohexanol;(1S,2S)-3-amino-1-(3-((E)-2-(1-hydroxycyclohexyl)vinyl)phenyl)propane-1,2-diol;(1R,2R)-3-amino-1-(3-((E)-2-(1-hydroxycyclohexyl)vinyl)phenyl)propane-1,2-diol;(E)-1-(5-(3-amino-1-hydroxypropyl)-2-methoxystyryl)cyclohexanol;(E)-1-(3-(3-amino-1-hydroxypropyl)-4-chloro styryl)cyclohexanol;(E)-1-(3-(3-amino-1-hydroxypropyl)-4-methylstyryl)cyclohexanol;(E)-1-(3-(3-amino-1-hydroxypropyl)-5-methylstyryl)cyclohexanol;(1S,2R)-3- ...

Styrenyl Derivative Compounds for Treating Ophthalmic Diseases and Disorders

The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are styrenyl derivative compounds, including but not limited to stilbene derivative compounds, and compositions comprising these compounds, that are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease. 184.-. (canceled)86. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein Ris alkyl.87. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein Ris aryl.88. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein Ris carbocyclyl.89. The compound of claim 88 , or the pharmaceutically acceptable salt thereof claim 88 , wherein Ris cyclohexyl.90. The compound of claim 88 , or the pharmaceutically acceptable salt thereof claim 88 , wherein Ris cyclohexenyl.91. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein Ris heteroaryl.92. The compound of claim 85 , or the pharmaceutically acceptable salt thereof claim 85 , wherein Ris heterocyclyl.94. The compound of claim 93 , or the pharmaceutically acceptable salt thereof claim 93 , wherein Ris alkyl.95. The compound of claim 93 , or the pharmaceutically acceptable salt thereof claim 93 , wherein Ris aryl.96. The compound of claim 93 , or the pharmaceutically acceptable salt thereof claim 93 , wherein Ris carbocyclyl.97. The compound of claim 96 , or the pharmaceutically acceptable salt thereof claim 96 , wherein Ris cyclohexyl.98. The compound of claim 96 , or the pharmaceutically acceptable salt thereof claim 96 , wherein Ris cyclohexenyl.99. A compound claim 96 , or the pharmaceutically acceptable salt thereof claim 96 , selected from:(S,E)-1-(3-(1-aminopropan-2-yloxy)styryl)cyclohexanol;(E)-1-(3 ...

PROCESS FOR THE PREPARATION OF PERFLUOROALKYLCYANO- OR PERFLUOROALKYLCYANOFLUOROBORATES

The invention relates to a process for the preparation of salts having perfluoroalkyltricyano- or perfluoroalkylcyanofluoroborate anions, ((per)fluoro)phenyltricyano- or ((per)fluoro)phenylcyanofluoroborate anions, phenyltricyanoborate anions which are mono- or disubstituted by perfluoroalkyl groups having 1 to 4 C atoms or phenylcyanofluoroborate anions which are mono- or disubstituted by perfluoroalkyl groups having 1 to 4 C atoms, by reaction of alkali metal trifluoroperfluoroalkylborate with trialkylsilyl cyanide and a subsequent salt-exchange reaction or by direct reaction of an organic trifluoroperfluoroalkyl borate with trialkylsilyl cyanide. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. A salt of formula III{'br': None, 'sup': a+', '−, 'sub': f', 'x', 'y', 'a, 'M[B(R)(CN)(F)]\u2003\u2003III,'}where{'sup': 'a+', 'M is a lithium, potassium, sodium, caesium or rubidium salt,'}{'sub': f', '6', '5', '6', '5, 'Rdenotes a linear or branched perfluorinated alkyl group having 1 to 4 C atoms, CF, CH, partially fluorinated phenyl, or phenyl which is mono- or disubstituted by a perfluoroalkyl group having 1 to 4 C atoms, where the perfluoroalkyl group is selected independently of one another,'}a is 1,x is 1, 2 or 3,{'sub': f', '6', '5, 'y is 0, 1 or 2, where 0 is excluded for R═CH, and'}x+y is 3.11. A salt according to claim 10 , that is potassium trifluoromethyltricyanoborate claim 10 , potassium pentafluoroethyltricyanoborate claim 10 , potassium heptafluoropropyltricyanoborate claim 10 , potassium trifluoromethyldicyanofluoroborate claim 10 , potassium pentafluoroethyldicyanofluoroborate claim 10 , potassium heptafluoropropyldicyanofluoroborate claim 10 , potassium trifluoromethylmonocyanodifluoroborate claim 10 , potassium pentafluoromethylmonocyanodifluoroborate claim 10 , potassium heptafluoropropylmonocyanodifluoroborate claim 10 , potassium nonafluorobutylmonocyanodifluoroborate claim 10 ...

Link-Plate Connection For Monopole Reinforcing Bars

Reinforcing bars include load transfer connectors. A link plate includes openings that mate with the load transfer connectors to overlie the splice between reinforcing bars being spliced. A cover plate may be fastened over the link plate.

FLUORIDE ION BATTERY ELECTROLYTE COMPOSITIONS

A fluoride ion battery includes a substantially lithium-free anode and cathode. At least one of the anode or cathode contains fluorine, and a substantially lithium-free liquid electrolyte is used for charge transport. The electrolyte is liquid at temperatures below about 200 degrees Celsius, and can be formed from an organic-soluble fluoride salt dissolved in selected classes of solvents. 1. An electrolyte comprising an organic-soluble fluoride salt containing at least one of alkylammonium or substituted alkyl ammonium cations RRRRNF , where R , R , Rand Rmay each be separately a substituted or unsubstituted , linear or branched , Cto Caliphatic or cyclic aliphatic , fluoroalkyl , oligo(ethyleneglycol) , aryl or substituted aryl group.235.-. (canceled) This application claims the benefit of U.S. Provisional Application No. 61/285,903, filed Dec. 11, 2009, the disclosure of which is incorporated by reference herein.The present invention relates to non-aqueous electrochemical cells based on fluoride ion transfer, suitable liquid electrolyte compositions containing fluoride ion salts, and to their use in electrochemical cells, including batteries, capacitors, supercapacitors, and galvanic cells.A battery generally includes a positive electrode (cathode during discharge), a negative electrode (anode during discharge) and an electrolyte for ion transport. The electrolyte can contain one or more ionic species that that act as charge carriers. Many widely available battery systems are based on cation electrode reactions, with electrodes capturing or releasing a cation from an electrolyte and balancing the charge with an electron from the external circuit. Because of its very low electrochemical oxidation/reduction potential and light weight, the element lithium is commonly used in cation based battery systems. Both lithium and lithium-ion batteries are commercially available and widely used.However, the electrochemistry of lithium metal or lithium containing electrodes ...

CATALYST COMPRISING A MIXTURE OF AN AFX-STRUCTURE ZEOLITE AND A BEA-STRUCTURE ZEOLITE AND AT LEAST ONE TRANSITION METAL FOR SELECTIVE REDUCTION OF NOX

The invention relates to a catalyst comprising a mixture of AFX-structure and BEA-structure zeolites and at least one additional transition metal, to the process for preparing same and to the use thereof for the selective catalytic reduction of NOx in the presence of a reducing agent such as NHor H. 1. A process for preparing a catalyst comprising a mixture of AFX-structure and BEA-structure zeolites , and at least one transition metal , comprising at least the following steps:{'sub': 2', '2', '3', '2', '2', '3', 'ze', '2', '2', '3', '2', '2', '3', '2', '2', '3', 'ze, 'i) mixing, in aqueous medium, of an FAU zeolite having an SiO/AlOmolar ratio of between 30 and 100 with at least one FAU-structure zeolite having an SiO/AlOmolar ratio of between 2 and 30 (upper limit excluded), and wherein the mathematical parameter, P, corresponding to the mass percentage of the FAU zeolite with an SiO/AlOmolar ratio of between 30 and 100, in its anhydrous form (expressed in %) in the mixture of FAU zeolites, multiplied by the SiO/AlOmolar ratio of the same FAU zeolite with an SiO/AlOmolar ratio of between 30 and 100, is such that: 3250 Подробнее

1,2-DISUBSTITUTED CYCLOBUTYL COMPOUNDS

The invention refers to compounds of general formula (I) 114-. (canceled)16. The compound according to claim 15 , wherein Ris selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl.17. The compound according to claim 16 , wherein Ris selected from substituted or unsubstituted C-Caryl or substituted or unsubstituted 5- to 10-membered heteroaryl.19. The compound according to claim 15 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 15 , substituted or unsubstituted alkyl claim 15 , and substituted or unsubstituted cycloalkyl claim 15 , or Rand R claim 15 , together with the bridging nitrogen atom to which they are attached claim 15 , form a substituted or unsubstituted non-aromatic heterocyclyl.20. The compound according to claim 19 , wherein Rand R claim 19 , together with the bridging nitrogen atom to which they are attached claim 19 , form a substituted or unsubstituted 5- to 10-membered non-aromatic heterocyclyl.22. The compound according to claim 15 , which is selected from:1-(((1S,2R)-2-(Phenoxymethyl)cyclobutyl)methyl)pyrrolidine,4-(((1S,2R)-2-(Phenoxymethyl)cyclobutyl)methyl)morpholine,4-methyl-1-(((1S,2R)-2-(Phenoxymethyl)cyclobutyl)methyl)piperidine,1-(((1S,2R)-2-((3,4-Dichlorophenoxy)methyl)cyclobutyl)methyl)pyrrolidine,4-(((1S,2R)-2-((3,4-Dichlorophenoxy)methyl)cyclobutyl)methyl)morpholine,1-(((1S,2R)-2-((3,4-Dichlorophenoxy)methyl)cyclobutyl)methyl)-4-methylpipendine,4-Methyl-1-(((1S,2R)-2-(((1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)methyl)cyclobutyl)methyl)piperidine,4-Methyl-1-(((1S,2R)-2-(((1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)oxy)methyl)cyclobutyl)methyl)piperidine,1-Methyl-3-(((1R,2S)-2-(pyrrolidin-1-ylmethyl)cyclobutyl)methoxy)-5-(trifluoromethyl)-1H-pyrazole,4-(((1S,2R)-2-(((1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)methyl)cyclobutyl)methyl)morpholine,1-Methyl-5-(((1R,2S)-2-(pyrrolidin-1-ylmethyl)cyclobutyl)methoxy)-3-( ...

METHOD FOR COUPLING A FIRST COMPOUND TO A SECOND COMPOUND

The present disclosure describes a method of coupling a first compound to a second compound, the method comprising: providing the first compound having a fluorosulfonate substituent; providing the second compound comprising an amine; and reacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture under conditions effective to couple the first compound to the second compound. The present disclosure further describes a one-pot method for coupling a first compound to a second compound. 1. A method of coupling a first compound to a second compound , the method comprising:providing the first compound having a fluorosulfonate substituent, the first compound comprising an aryl or a heteroaryl group;providing the second compound comprising an amine; andreacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture under conditions effective to couple the first compound to the second compound.2. The method of claim 1 , wherein the reaction mixture further includes a ligand.3. The method of wherein the catalyst is generated in-situ from a palladium precatalyst.4. The method of wherein the catalyst is generated in-situ from a palladium precatalyst claim 3 , the palladium precatalyst is selected from the group consisting of: Palladium(II) acetate claim 3 , Palladium(II) chloride claim 3 , Dichlorobis(acetonitrile)palladium(II) claim 3 , Dichlorobis(benzonitrile)palladium(II) claim 3 , Allylpalladium chloride dimer claim 3 , Palladium(II) acetylacetonate claim 3 , Palladium(II) bromide claim 3 , Bis(dibenzylideneacetone)palladium(0) claim 3 , Bis(2-methylallyl)palladium chloride dimer claim 3 , Crotylpalladium chloride dimer claim 3 , Dichloro(1 claim 3 ,5-cyclooctadiene)palladium(II) claim 3 , Dichloro(norbornadiene)palladium(II) claim 3 , Palladium(II) ...

Process and intermediates for the preparation of benzo[b]thiophene compounds

A process for preparing compounds of formula (I), or a salt or solvate thereof, including Brexpiprazole, which process comprises cyclization of a compound of formula (II) or (III), or a salt or solvate thereof. The invention also refers to intermediates of said process.

Styrenyl Derivative Compounds for Treating Ophthalmic Diseases and Disorders

The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are styrenyl derivative compounds, including but not limited to stilbene derivative compounds, and compositions comprising these compounds, that are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease.

POLYMERIC AND SOLID-SUPPORTED CATALYSTS, AND METHODS OF DIGESTING CELLULOSIC MATERIALS USING SUCH CATALYSTS

Provided herein are catalysts useful in non-enzymatic saccharification processes. The catalysts can be polymeric catalysts or solid-supported catalysts with acidic and ionic moieties. Provided are also methods for hydrolyzing cellulosic materials into monosaccharides and/or oligosaccharides using the catalysts described herein. 1. A catalyst comprising a solid support , acidic moieties attached to the solid support , and ionic moieties attached to the solid support ,wherein the solid support comprises a material, wherein the material is selected from the group consisting of carbon, silica, silica gel, alumina, magnesia, titania, zirconia, clays, magnesium silicate, silicon carbide, zeolites, ceramics, and any combinations thereof,wherein each acidic moiety independently has at least one Bronsted-Lowry acid, andwherein each ionic moiety independently has at least one nitrogen-containing cationic group or at least one phosphorous-containing cationic group, or a combination thereof.2. The catalyst of claim 1 , wherein each Bronsted-Lowry acid is independently selected from the group consisting of sulfonic acid claim 1 , phosphonic acid claim 1 , acetic acid claim 1 , isophthalic acid claim 1 , boronic acid claim 1 , and perfluorinated acid.3. The catalyst of claim 1 , wherein one or more of the acidic moieties are directly attached to the solid support.4. The catalyst of claim 1 , wherein one or more of the acidic moieties are attached to the solid support by a linker.5. The catalyst of claim 1 , wherein each ionic moiety is selected from the group consisting of pyrrolium claim 1 , imidazolium claim 1 , pyrazolium claim 1 , oxazolium claim 1 , thiazolium claim 1 , pyridinium claim 1 , pyrimidinium claim 1 , pyrazinium claim 1 , pyradizimium claim 1 , thiazinium claim 1 , morpholinium claim 1 , piperidinium claim 1 , piperizinium claim 1 , pyrollizinium claim 1 , phosphonium claim 1 , trimethyl phosphonium claim 1 , triethyl phosphonium claim 1 , tripropyl phosphonium ...

Antifungal Compounds

Compounds and compositions having antifungal activity, and methods of using the antifungal compounds and compositions, are described for use in treating fungal infections. 2. A pharmaceutical composition comprising the compound of claim 1 , and a suitable pharmaceutical carrier.3. A method of treating a fungal infection claim 1 , comprising administering an effective amount of the compound of .4. The method of claim 3 , wherein the compound is administered to a subject.5. The method of claim 4 , wherein the subject is a human subject.6. The method of claim 3 , wherein the compound is administered to a plant or crop. This application claims priority from U.S. Provisional Application Ser. No. 62/595,975 filed Dec. 7, 2017, and 62/431,679 filed Dec. 8, 2016, the entire disclosure of which is incorporated herein by this reference.The presently-disclosed subject matter generally relates to compounds and compositions having antifungal activity, and methods of using the antifungal compounds and compositions, including use for treating fungal infections.Fungal infections have been rapidly increasing worldwide and present a continuous threat to human health.Drug resistance among fungal pathogens is an increasing problem, thus identification and development of compounds capable of overcoming resistance is a requisite.The conventional antifungal agents used in the treatment of human fungal infections are azoles (e.g., fluconazole (FLC), voriconazole (VOR), itraconazole (ITC), and posaconazoe (POS)), polyenes (e.g., amphotericin B (AmB)) (), echinocandins (e.g., anidulafungin, caspofungin and micafungin), and allylamines (e.g., terbinafine and naftifine) ().The present inventors previously showed that kanamycin B (KANB) and tobramycin (TOB) analogues with linear alkyl chains comprising 12 and 14 carbons (Cand C; ) display promising antifungal potency against and spp.Unlike the parent aminoglycoside antibiotics, the Cand CKANB and TOB analogues appear to inhibit fungi by ...

PROCESS FOR PRODUCING ALKYNYLKETONE DERIVATIVE

The present invention relates to a Sonogashira-Carbonylation reaction using two types of gas, as well as novel crystals which can control a heat of the said reaction and the process of producing the same. In addition, the present invention relates to a ligand (additive) to prevent the deactivation of a palladium catalyst. 2. The process according to claim 1 , wherein R is methyl.3. The process according to claim 1 , wherein the palladium catalyst is Pd(dba) claim 1 , PdCldppf claim 1 , PdCl(PPh) claim 1 , Pd(OAc) claim 1 , Pd(PPh) claim 1 , Pd/C claim 1 , PdCl claim 1 , Pd-PEPPSI™-IPr claim 1 , Bis[cinnamyl palladium Cl] claim 1 , PdCl(Xantphos) or Pd(OH).4. The process according to claim 1 , wherein the phosphine ligand is Xantphos claim 1 , P(2-furyl) claim 1 , PPh claim 1 , P(o-tol) claim 1 , P(OPh) claim 1 , P(OMe) claim 1 , dppp claim 1 , dppb claim 1 , dppf claim 1 , BINAP claim 1 , X-Phos claim 1 , P(t-Bu) claim 1 , P(Oi-Pr) claim 1 , P(p-MeOPh)or DPEPhos.5. The process according to claim 1 , wherein the catalyst comprising Group 11 element is copper iodide(I) claim 1 , copper iodide(II) claim 1 , copper chloride(I) claim 1 , copper chloride(II) claim 1 , copper acetate(I) claim 1 , copper acetate(II) claim 1 , copper oxide(II) claim 1 , copper bromide(I) claim 1 , copper bromide(II) or silver acetate.6. The process according to claim 1 , wherein the base is N-methylmorpholine claim 1 , triethylamine claim 1 , diisopropylethylamine claim 1 , pyridine claim 1 , DABCO claim 1 , N claim 1 ,N-dimethylbenzylamine claim 1 , N claim 1 ,N-dimethylaniline claim 1 , sodium acetate claim 1 , potassium carbonate claim 1 , sodium carbonate or potassium phosphate.8. The process according to claim 7 , wherein Ris a group represented by formula: —Y—R claim 7 , wherein —Y— is alkylene which may be intervened with —O—; and Ris phenyl unsubstituted or substituted with a substituent selected from a substituent group p [substituent group p: halogen claim 7 , carboxy claim 7 , ...

PHOSPHORUS-CONTAINING CATALYSTS

The invention provides compounds of general structure I: (Ar—Ar—Ar-E-P(=D)R-)MXL″. In this structure: •Ar, Arand Arare aromatic groups wherein: —Arand Arare in a 1,3 relationship on Ar, —each of Ar, Arand Aroptionally comprises one or more ring substituents of formula YR′wherein each Y independently is absent or is O, S, B, N or Si and each R′ is independently H, halogen, alkyl, cycloalkyl, aryl or heteroaryl and r is 1, 2 or 3, where r is 1 if Y is absent or is O or S, 2 if Y is B or N and 3 if Y is Si, —Ar, Arand Arare each independently carbocyclic or heterocyclic and each is independently monocyclic, bicyclic or polycyclic and each ring of each of Ar, Arand Arindependently has 5, 6 or 7 ring atoms; •E is absent or is selected from the group consisting of O, S, NR″, SiR″, AsR″and CR″; •M is a complexing metal; •X is selected from the group consisting of H, F, Br, CI, I, OTf, dba (dibenzylidene acetone), OC(═O)CFand OAc; •L is selected from the group consisting of PR″, NR″, OR″, SR″, SiR″, AsR″, alkene, alkyne, aryl and heteroaryl, each of said alkene, alkyne, aryl and heteroaryl being optionally substituted, for example with one or more halogens and/or with one or more R groups as defined herein; •each R is independently alkyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl or -, heteroaryl; •D is absent or is ═S or —O or —Z-linker-Z—, where each Z independently is O or NH or N-alkyl and linker is an alkyl chain of 2-5 carbon atoms in length; •each R″ is independently H, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each other than H being optionally substituted, or R″is —Z-linker-Z— as defined above; and •m is 0 or 1 or 2; wherein if m is 0, n is 1, n′ and n″ are 0 and -- is absent; and if m is 1 or 2, n is 1 or 2 and n′ and n″ are integers such that the coordination sphere of M is filled, and D is absent. 2. The compound of wherein m is 1 or 2 and M is bonded to a ring atom of Arortho to E.3. The compound of or wherein E is O or S or NR″.4. The ...

COMPOUNDS FOR TREATING DENGUE VIRUS INFECTIONS AND OTHER INFECTIONS

Provided herein are compounds, pharmaceutical compositions, methods, and kits for treating viral infections (e.g., Dengue viral infections). In certain embodiments, compounds useful in the methods described herein are of Formula (I) or (II). 2. The method of claim 1 , wherein the compound is of Formula (I) claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , hydrate claim 1 , polymorph claim 1 , co-crystal claim 1 , tautomer claim 1 , stereoisomer claim 1 , isotopically labeled derivative claim 1 , or prodrug thereof.23. The method of or claim 1 , wherein Ring A is optionally substituted phenyl.28. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —NR—.29. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —OC(═O)—.30. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —NRC(═O)—.31. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Z is —NRS(═O)—.32. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Y is —O—.33. The method of any one of - claim 1 , claim 1 , claim 1 , - claim 1 , claim 1 , claim 1 , and - claim 1 , wherein Y is —C(R)—.34. The method of claim 33 , wherein Y is —C(CN)H—.35. The method of any one of - claim 33 , claim 33 , claim 33 , claim 33 , and - claim 33 , wherein Xis —Cl.36. The method of any one of - claim 33 , claim 33 , claim 33 , claim 33 , and - claim 33 , wherein Xis hydrogen.37. The method of any one of - claim 33 , claim 33 , claim 33 , claim 33 , and - claim 33 , wherein Xis optionally substituted Calkyl.38. The method of claim 37 , wherein Xis unsubstituted Calkyl.39. The method of or claim 37 , wherein Xis methyl.40. The method of any one of claim 37 , claim 37 , claim 37 , and - claim 37 , ...

COMPOUNDS AND METHODS FOR THE TREATMENT OF CANCER

Compositions and methods relating to induction of cell death such as in cancer cells are disclosed. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds in connection with modification of procaspases such as procaspase-3 are disclosed. In various embodiments, the compounds and compositions are capable of activation of procaspase-3. 2. (canceled)4. The method of wherein the pharmaceutically acceptable carrier comprises an excipient selected from a sugar claim 1 , a cellulose preparation claim 1 , a crosslinked polyvinyl pyrrolidone claim 1 , agar claim 1 , and alginic acid or a salt thereof.5. The method of wherein the composition is formulated for delayed release.6. The method of wherein the composition comprises a sugar or a cellulose preparation; wherein the sugar is lactose claim 4 , sucrose claim 4 , mannitol claim 4 , sorbitol claim 4 , or a combination thereof; or the cellulose preparation comprises maize starch claim 4 , wheat starch claim 4 , rice starch claim 4 , potato starch claim 4 , gelatin claim 4 , gum claim 4 , tragacanth claim 4 , methyl cellulose claim 4 , hydroxypropylmethyl-cellulose claim 4 , or sodium carboxymethylcellulose.7. The method of wherein the composition is administered orally in the form of a tablet claim 1 , dragee claim 1 , pill claim 1 , capsule claim 1 , gel claim 1 , syrup claim 1 , slurry claim 1 , elixir claim 1 , suspension claim 1 , or solution.8. The method of wherein the composition is formulated to release the compound only when the composition reaches the small intestine.9. The method of wherein the cancer is adrenal cancer claim 1 , brain cancer claim 1 , breast cancer claim 1 , colon cancer claim 1 , leukemia claim 1 , liver cancer claim 1 , lung cancer claim 1 , lymphoma claim 1 , melanoma claim 1 , neuroblastoma claim 1 , or renal cancer.11. The method of wherein Rand ...

PROCESS FOR MANUFACTURING A CYCLIC UREA ADDUCT OF AN ETHYLENEAMINE COMPOUND

A process is provided for manufacturing a cyclic urea adduct of an ethyleneamine compound, the ethyleneamine compound having a linear —NH—CH—CH—NH— group. The process includes, in an absorption step, contacting a liquid medium comprising an ethyleneamine compound having a linear —NH—CH—CH—NH— group with a CO-containing gas stream at a pressure of from about 1 to about 20 bara, resulting in the formation of a liquid medium into which COhas been absorbed. The process further includes bringing the liquid medium to cyclic urea formation conditions, and, in an urea formation step, forming cyclic urea adduct of the ethyleneamine compound, urea formation conditions including a temperature of at least about 120° C., wherein the total pressure at the end of the urea formation step is at most about 20 bara, and wherein the temperature in the absorption step is lower than the temperature in the urea formation step. 1. A process for manufacturing a cyclic urea adduct of an ethyleneamine compound , the ethyleneamine compound having a linear —NH—CH2-CH2-NH— group , the process comprising the steps of:{'sub': 2', '2', '2', '2, 'in an absorption step, contacting a liquid medium comprising an ethyleneamine compound having a linear —NH—CH—CH—NH— group with a CO-containing gas stream at a pressure of from about 1 to about 20 bara, resulting in the formation of a liquid medium into which COhas been absorbed,'}bringing the liquid medium to cyclic urea formation conditions, andin an urea formation step, forming cyclic urea adduct of the ethyleneamine compound, urea formation conditions including a temperature of at least about 120° C., wherein the total pressure at the end of the urea formation step is at most about 20 bara, and wherein the temperature in the absorption step is lower than the temperature in the urea formation step.2. The process according to claim 1 , wherein the CO-containing gas stream comprises at least about 95 vol. % of CO.3. The process according to claim 1 , ...

IONIC LIQUIDS AND PREPARATION METHOD THEREOF

The present disclosure provides an ionic liquid and a preparation method thereof, in particular, the present disclosure provides an ionic liquid whose halogen anions content and moisture content are low, and a method for preparing the same. The total content of halogen anions in the ionic liquid is less than 10 ppm, and moisture content in the ionic liquid is less than 50 ppm. The ionic liquid prepared by the method of the present disclosure is suitable for electrochemical systems which have high requirements for moisture content, such as lithium ion secondary batteries and electrochemical supercapacitors. 1. An ionic liquid , wherein a total content of halogen anions in the ionic liquid is less than 10 ppm , and moisture content in the ionic liquid is less than 50 ppm; the halogen anions are Cl , Br and I.2. The ionic liquid of claim 1 , wherein the total content of halogen anions in the ionic liquid is less than 5 ppm.5. A preparation method of the ionic liquid as described in claim 1 , comprising the following steps: [{'br': None, 'sub': 4', '5', '6', '1', '2', '3', '4', '5', '6', '1', '2', '3, 'sup': +', '−', '+', '−, 'QQQN+[QQQNH]A→[QQQNH]A+QQQN\u2003\u2003(a); or'}, {'br': None, 'sub': 4', '5', '6', '1', '2', '3', '4', '5', '6', '1', '2', '3, 'sup': +', '−', '+', '−, 'QQQP+[QQQPH]A→[QQQPH]A+QQQP\u2003\u2003(b); or'}, {'br': None, 'sub': 4', '5', '6', '1', '2', '3', '4', '5', '6', '1', '2', '3, 'sup': +', '−', '+', '−, 'QQQN+[QQQPH]A→[QQQNH]A+QQQP\u2003\u2003(c); or'}, {'br': None, 'sub': 4', '5', '6', '1', '2', '3', '4', '5', '6', '1', '2', '3, 'sup': +', '−', '+', '−, 'QQQP+[QQQNH]A→[QQQPH]A+QQQN\u2003\u2003(d);'}], 'Step 1: preparing an ammonium salt or a phosphonium salt, reaction equations as below [{'br': None, 'sub': 4', '5', '6', '3', '4', '5', '6', '2, 'sup': +', '−', '+', '−, '[QQQNH]A+RCOR′→[QQQNR]A+R′OH+CO; or'}, {'br': None, 'sub': 4', '5', '6', '3', '4', '5', '6', '2, 'sup': +', '−', '+', '−, '[QQQPH]A+RCOR′→[QQQPR]A+R′OH+CO;'}], 'Step 2: the ...

Nicotinic receptor non-competitive antagonists

The present invention relates to compounds that modulate nicotinic receptors as non-competitive antagonists, methods for their synthesis, methods for use, and their pharmaceutical compositions.

1,4-Disubstituted Piperidines, 1,4-Disubstituted Piperazines, 1,4-Disubstituted Diazepines, and 1,3-Disubstituted Pyrrolidine Compounds

The present invention is directed to 1,4-disubstituted piperidines, 1,4-disubstituted piperazines, 1,4-disubstituted diazepanes, and 1,3-disubstituted pyrrolidine compounds and their use.

Peripherally-acting cannabinoid receptor agonists for chronic pain

Peripherally acting cannabinoid agonist compounds, pharmaceutical compositions, and methods of using them are presented.

ADENYLYL CYCLASE INHIBITORS FOR NEUROPATHIC AND INFLAMMATORY PAIN

The invention generally relates to adenylyl cyclase inhibitor compounds and methods for treating neuropathic or inflammatory pain by using those compounds. 128-. (canceled)301. The method of claim , wherein the adenylyl cyclase is adenylyl cyclase type I (AC1). This application claims the benefit of and priority to U.S. Provisional Application No. 62/116,686, filed Feb. 16, 2015, which is incorporated by reference herein in its entirety.The invention generally relates to adenylyl cyclase inhibitors and methods of use thereof.Adenylyl cyclases are important mediators of signaling through G protein-coupled receptors. Adenylyl cyclase type 1 (AC1) belongs to a family of adenylyl cyclases that are stimulated by calcium in a calmodulin-dependent manner. Notably, AC1 is associated with chronic pain responses in several regions of the central nervous system. Accordingly, inhibition of AC1 has resulted in analgesic effects in both neuroinflammatory and neuropathic pain in rodent models. A dearth of AC1 inhibiting compounds and an inability to efficiently synthesize them means that their analgesic benefits cannot be widely realized and people continue to suffer from neuropathic and inflammatory pain.The invention generally relates to potent adenylyl cyclase inhibitor compounds. The invention further relates to methods for treating neuropathic or inflammatory pain by delivering adenylyl cyclase inhibitor compounds of the invention. Methods of the invention also provide for palladium-catalyzed γ-arylation of tertiary allylic amines and the synthesis of the disclosed AC1 inhibitor compounds as well as drug molecules such as naftifine, cinarizine, flunarizine, and analogs thereof. Heck arylation methods of the invention provide increased regio- and stereo-selectivity and yield over known methods.In certain aspects, the invention provides a compound of formula (I):wherein: X is carbon or nitrogen; n is 0 or 1; Ris selected from aryl, alkenyl, or alkyl optionally substituted by: ...

PARACYCLOPHANE-BASED LIGANDS, THEIR PREPARATION AND USE IN CATALYSIS

A substituted paracyclophane of formula (I) is provided 2. The metal complex according to wherein the metal compound is a compound of palladium (Pd) claim 1 , platinum (Pt) claim 1 , rhodium (Rh) claim 1 , iridium (Ir) or ruthenium (Ru).3. The metal complex according to wherein the substituted paracyclophane (I) is substantially enantiomerically-pure.4. The metal complex according to wherein the metal complex is supported on a solid support.5. The metal complex according to wherein the substituted paracyclophane (I) is substantially enantiomerically-pure.6. A method of asymmetrically hydrogenating a substrate claim 2 , comprising performing the hydrogenation in the presence of a metal complex according to .7. A method of catalyzing a reaction claim 2 , comprising performing the reaction in the presence of a metal complex according to claim 2 , wherein the reaction is selected from the group consisting of carbon-carbon coupling reactions claim 2 , enantioselective isomerization of olefins claim 2 , asymmetric hydroboration reactions claim 2 , asymmetric cyclisation of olefinic aldehydes claim 2 , asymmetric arylation reactions claim 2 , asymmetric alkylation reactions and amination of aryl halides (Hartwig-Buchwald reaction). This application is a Division of U.S. patent application Ser. No.12/675,918, filed Oct. 22, 2010, which is the U.S. National Phase filing of PCT International Application No. PCT/GB2008/050730, filed Aug. 21, 2008, and claims priority of British Patent Application No. 0716714.1, filed Aug. 29, 2007, the disclosures of which applications are incorporated herein by reference in their entirety.This invention relates to ligands used in transition metal-catalysed reactions and in particular to substituted paracyclophanes.Paracyclophanes and in particular [2.2]-paracyclophane derivatives are established ligands for transition metal-catalysed asymmetric reactions (see for example, S. E. Gibson and J. D. Knight, 2003, 1, 1256-1269). Of these, ...

Phenyl-Piperazine Derivatives As Serotonin Reuptake Inhibitors

The invention provides compounds represented by the general formula I 115-. (canceled)16. A pharmaceutical composition , comprising:1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine or a hydrobromic acid addition salt thereof, andat least one pharmaceutically acceptable carrier or diluent.17. The composition of claim 16 , wherein the composition comprises a hydrobromic acid addition salt of 1-[2-(2 claim 16 ,4-dimethylphenylsulfanyl)phenyl]piperazine.18. The composition of claim 17 , wherein the composition is a tablet.19. The composition of claim 18 , wherein the composition comprises 1-[2-(2 claim 18 ,4-dimethylphenylsulfanyl)phenyl]piperazine in an amount of from 0.01 mg to 100 mg.201. A method for the treatment of an affective disorder in a human in need thereof claim 18 , comprising administering to the human an amount of the composition of claim comprising a therapeutically effective amount of 1-[2-(2 claim 18 ,4-dimethylphenylsulfanyl)phenyl]piperazine or a hydrobromic acid addition salt thereof.21. The method of claim 20 , wherein the affective disorder is depression.22. The method of claim 20 , wherein the affective disorder is an anxiety disorder.23. The method of claim 22 , wherein the anxiety disorder is general anxiety disorder or panic disorder.24. The method of claim 20 , wherein the affective disorder is obsessive compulsive disorder.25. The method of claim 20 , wherein the composition comprises a therapeutically effective amount of a hydrobromic acid addition salt of 1-[2-(2 claim 20 ,4-dimethylphenylsulfanyl)phenyl]piperazine.26. The method of claim 25 , wherein the affective disorder is depression.27. The method of claim 25 , wherein the affective disorder is an anxiety disorder.28. The method of claim 27 , wherein the anxiety disorder is general anxiety disorder or panic disorder.29. The method of claim 25 , wherein the affective disorder is obsessive compulsive disorder.30. The method of claim 25 , wherein the composition is a tablet.31. The ...

EMM-23 Molecular Sieve Materials, Its Synthesis and Use

A new molecular sieve material is designated as EMM-23 and has, in its as-calcined form, an X-ray diffraction pattern including the following peaks in Table 1: 3. The material of claim 2 , wherein X includes one or more of B claim 2 , Al claim 2 , Fe claim 2 , and Ga claim 2 , and Y includes one or more of Si claim 2 , Ge claim 2 , Sn claim 2 , Ti claim 2 , and Zr.4. The material of claim 2 , wherein X includes aluminum claim 2 , and Y includes silicon and/or germanium.7. The material of claim 6 , wherein X includes aluminum claim 6 , and Y includes silicon.8. The material of claim 6 , wherein X includes one or more of B claim 6 , Al claim 6 , Fe claim 6 , or Ga claim 6 , and Y includes one or more of Si claim 6 , Ge claim 6 , Sn claim 6 , Ti claim 6 , or Zr.9. The material of claim 6 , wherein F includes one or more of F claim 6 , HF claim 6 , NHF claim 6 , and NHHF.10. The material of claim 6 , wherein Q comprises 1 claim 6 ,5-bis(N-propylpyrrolidinium)pentane dications and/or 1 claim 6 ,6-bis(N-propylpyrrolidinium)hexane dications.11. A process for producing the molecular sieve material of claim 6 , the process comprising the steps of:(i) preparing a synthesis mixture capable of forming said material, said mixture comprising water, a source of hydroxyl ions, a source of an oxide of a tetravalent element Y, a source of a trivalent element X, optionally a source of fluoride ions, and a directing agent (Q) comprising 1,5-bis(N-propylpyrrolidinium)pentane dications and/or 1,6-bis(N-propylpyrrolidinium)hexane dications, and said mixture having a composition, in terms of mole ratios, within the following ranges:{'sub': 2', '2', '3, 'YO/XOat least 10;'}{'sub': 2', '2, 'HO/YOabout 0.5 to about 30;'}{'sup': '−', 'sub': '2', 'OH/YOabout 0.1 to about 1.0;'}{'sub': '2', 'F/YOabout 0.0 to about 0.25; and'}{'sub': '2', 'Q/YOabout 0.05 to about 0.5;'}(ii) heating said mixture under crystallization conditions including a temperature of from about 100° C. to about 200° C. and a ...

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

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

Photopolymer formulation for production of holographic media comprising borates with low tg

The invention relates to a photopolymer formulation comprising a component reactive toward isocyanates, a polyisocyanate component, a writing monomer and a photoinitiator containing at least one dye and a coinitiator, characterized in that the coinitiator contains at least one substance of the formula (Ia) The invention further provides a process for preparing the specific coinitiators and the coinitiators obtainable by this process, and additionally a process for producing a holographic medium using the specific coinitiators, and a holographic medium obtainable using the inventive photopolymer formulation. The invention further relates to a laminate structure comprising an inventive holographic medium and likewise specific borates suitable as coinitiators.

Amino- or ammonium-containing sulfonic acid, phosphonic acid and carboxylic acid derivatives and their medical use

The present invention relates to amino- or ammonium-containing sulfonic acid, phosphonic acid and carboxylic acid derivatives, in particular the compounds of formula 1, 2, 3, 4, 5 or 6 and their medical use, including their use in treatment, prevention or amelioration of an inflammatory, autoimmune and/or allergic disorder.

PROCESS FOR MODIFYING ISOCYANATES WITH USE OF CYCLIC AMMONIUM SALTS AS CATALYST

The invention relates to a process for modifying isocyanates where at least one organic isocyanate with NCO functionality >1 is oligomerized in the presence of at least one catalyst, characterized in that the catalyst comprises, as isocyanatemodification catalysts, at least one cyclic ammonium salt having a cation of the formula (I) (formula I), where the N-containing substituents Rand Rare mutually independently identical or different aliphatic, cycloaliphatic, aromatic or araliphatic C, to Cmoieties which are saturated or unsaturated, linear or branched, optionally substituted and/or interrupted by heteroatoms from the group of oxygen, sulphur and nitrogen, and Y is a substituted or unsubstituted, linear or branched Cto Csegment optionally interrupted by heteroatoms from the group of oxygen, sulphur and nitrogen or else intempted by aromatic rings, and optionally containing other rings. The invention further relates to the use of such a catalyst. 2. The process as claimed in claim 1 , characterized in that Rand Rare mutually independently identical or different C-C-alkyl substituents claim 1 , preferably identical or different C-C-alkyl substituents and particularly preferably have a linear structure.3. The process as claimed in claim 1 , characterized in that Rand Rin formula I are mutually independently identical or different benzyl radicals optionally substituted on the aromatic ring.4. The process as claimed in any of the preceding claims claim 1 , characterized in that segment Y is C-C-alkylene chains optionally substituted and/or interrupted by heteroatoms from the group of oxygen claim 1 , sulfur claim 1 , nitrogen and also by aromatic rings and especially has a linear structure.5. The process as claimed in any of the preceding claims claim 1 , characterized in that the anion of the cyclic ammonium salt is selected from hydroxide claim 1 , alkanoate claim 1 , carboxylate claim 1 , heterocycles having at least one negatively charged nitrogen atom in the ring ...

Phosphine ligands for catalytic reactions

The disclosure is directed to: (a) phosphacycle ligands; (b) catalyst compositions comprising phosphacycle ligands; and (c) methods of using such phosphacycle ligands and catalyst compositions in bond forming reactions.

Catalytic Hydrogenation for the Preparation of Amines from Amide Acetals, Ketene N,O-Acetals or Ester Imides

The present invention relates to a process for the preparation of amines, comprising the following steps: Reaction of a (i) amide acetal of the general formula (I), or (ii) ketene N,O-acetal of the general formula (II), or (iii) ester imide of the general formula (III) with H 2 in the presence of a hydrogenation catalyst, where catalyst and amide acetal or ketene N,O-acetal or ester imide are used in a molar ratio of from 1:10 to 1:100 000 and where a hydrogen pressure of from 0.1 bar to 200 bar is established and where a temperature in the range of from 0° C. to 250° C. is established.

NON-ATP/CATALYTIC SITE p38 MITOGEN ACTIVATED PROTEIN KINASE INHIBITORS

Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases. 2. The compound of claim 1 , wherein Lis —CH—.3. The compound of claim 1 , wherein Lis —NH—SO—.4. The compound of claim 1 , wherein Lis —NHCO—.5. The compound of claim 1 , wherein Lis —CONH.6. The compound of claim 1 , wherein each of Rand Ris independently selected from hydrogen and Calkyl.7. The compound of claim 1 , wherein each of Rand Ris independently Calkyl.9. The compound of claim 1 , wherein Aris a 5 membered heteroaryl ring.10. The compound of claim 9 , wherein the 5 membered heteroaryl ring is selected from furan claim 9 , thiophene claim 9 , pyrrole claim 9 , and imidazole.13. A pharmaceutical composition comprising the compound of or a pharmaceutically acceptable salt thereof.14. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is an oral pharmaceutical composition.15. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is an oral dosage form.16. A method of treating an inflammatory disease in a patient comprising administering to a patient in need thereof a therapeutically effective amount of the compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein the inflammatory disease is selected from rheumatoid arthritis claim 1 , a cardiovascular disease claim 1 , multiple sclerosis claim 1 , inflammatory bowel disease claim 1 , chronic obstructive pulmonary disease (COPD) claim 1 , asthma claim 1 , acute respiratory distress syndrome (ARDS) claim 1 , and acute lung injury (ALI).17. The method of claim 16 , wherein the disease is a respiratory disease.18. The method of claim 16 , wherein administering comprises orally administering.19. The method of claim 16 , wherein administering comprises administering an oral dosage form comprising the compound.20. The method of claim 16 , wherein administering comprises ...

NICOTINIC ACETYLCHOLINE RECEPTOR SILENT AGONISTS

Derivatives of N,N-diethyl-N′-phenyl-piperazine, a silent agonist of the mammalian α7 nicotinic acetylcholine receptor, are provided. These silent agonists control the desensitization state of the receptor. Further provided are pharmaceutical compositions that allow the administration of the silent agonists of the disclosure to a subject animal or human in need of treatment for a pathological condition arising from such as inflammation. The novel silent agonists also may be co-administered to a patient simultaneously or consecutively with a type II positive allosteric modulator to modulate the activity of the receptor. 114-. (canceled)15. A method of modulating the activity of a nicotinic acetylcholine receptor in an animal or human subject by administering to said subject therapeutically effective doses of a silent agonist of the nicotinic acetylcholine receptor and a nicotinic acetylcholine receptor positive allosteric modulator (PAM).16. The method of claim 15 , wherein the silent agonist of the nicotinic acetylcholine receptor and the nicotinic acetylcholine receptor positive allosteric modulator (PAM) are administered to the subject simultaneously or as consecutive doses.18. The method of claim 15 , wherein the nicotinic acetylcholine receptor positive allosteric modulator (PAM) is a type II PAM.19. The method of claim 18 , wherein the nicotinic acetylcholine receptor positive allosteric modulator (PAM) is the type II PAM 1-(5-chloro-2 claim 18 ,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl )urea (PNU-120596).20. (canceled) This application claims priority to U.S. Provisional Application No. 62/241,885, entitled “DISSECTION OF N,N-DIETHYL-N′-PHENYLPIPERAZINES AS NICOTINIC RECEPTOR SILENT AGONISTS” filed on Oct. 15, 2015, the entirety of which is herein incorporated by reference.This invention was made with Government support under contract GM57481 awarded by the National Institutes of Health. The Government has certain rights in the invention.The present ...

ORGANO-1-OXA-4-AZONIUM CYCLOHEXANE COMPOUNDS

Novel 1-oxa-4-azonium cyclohexane salts are described. These compounds can be used as structure directing agents, and they overcome many of the typical problems associated with OSDA synthesis and subsequent zeolite synthesis. Methods for synthesis of the 1-oxa-4-azonium cyclohexane salts from a variety of starting materials are also described. A substituted hydrocarbon is added to water to form a mixture, and a 1-oxa-4-azacyclohexane derivative is then added. The reaction mixture stirred until a solution containing the 1-oxa-4-azonium cyclohexane salt is obtained. 1. A morpholinium compound comprising: {'chemistry': {'@id': 'CHEM-US-00001', '@num': '00001', 'img': {'@id': 'EMI-C00001', '@he': '19.47mm', '@wi': '31.24mm', '@file': 'US20180258058A1-20180913-C00001.TIF', '@alt': 'embedded image', '@img-content': 'chem', '@img-format': 'tif'}}, 'br': None, 'sub': 1', '2', '3', '4', '9', '10', '5', '6', '7', '8, 'sup': +', '−, '2-R-2-R-3-R-3-R-4-R-4-R-5-R-5-R-6-R-6-R-1-oxa-4-azoniumcyclohexane-X,\u2003\u2003Formula 1, 'a 1-oxa-4-azonium cyclohexane salt having a structure of{'sub': 1', '9', 'n', '2n+1', '10', 'n', '2n+1', 'p', '2p−1, 'wherein R-Rare independently selected from H or an alkyl group having the formula CH, Ris selected from an alkyl group having the formula CHwhere n is in the range from 1 to 4, benzyl, 1-methylnaphthalene, 2-methylnaphthalene and a non-olefinic alkyl group having the formula CHwhere p is in the range from 4 to 10, X is halide or hydroxide, and the total number of C atoms in the molecule is in the range of 4 to 16;'}or combinations thereof.2. The morpholinium compound of wherein X is hydroxide.3. The morpholinium compound of wherein R-Rare H.4. The morpholinium compound of wherein at least one of Rand Ris the alkyl group having the formula CH.5. The morpholinium compound of wherein at least one of R-Ris an alkyl group.6. The morpholinium compound of wherein at least one of Rand Ris an alkyl group having the formula CH.7. The morpholinium ...

Nicotinic Receptor Non-Competitive Antagonists

The present invention relates to compounds that modulate nicotinic receptors as non-competitive antagonists, methods for use, and their pharmaceutical compositions. 3. A method for treating nicotine addiction comprising administering the composition of to a patient in need of such treatment.4. The method of further comprising administering varenicline to the patient either concomitantly in the same pharmaceutical composition or in separate pharmaceutical compositions. This application is a continuation of U.S. application Ser. No. 15/877,725 filed Jan. 23, 2018 which is a continuation of U.S. application Ser. No. 15/360,393 filed Nov. 23, 2016 now abandoned, which is a continuation of U.S. Ser. No. 14/837,023 filed Aug. 27, 2015, now U.S. Pat. No. 9,532,974, which is a continuation of U.S. application Ser. No. 14/320,782 filed Jul. 1, 2014, now abandoned, which is a continuation of U.S. application Ser. No. 13/699,757, filed Mar. 22, 2013, now U.S. Pat. No. 8,809,397, which is a § 371 filing of PCT Application No. PCT/US2011/037630, with an International Filing Date of May 24, 2011, which claims priority to U.S. Provisional Patent Application Ser. No. 61/349,027, filed May 27, 2010 and U.S. Provisional Patent Application Ser. No. 61/375,606 filed Aug. 20, 2010; each of which is herein incorporated by reference in its entiretyThe present invention relates to compounds that modulate nicotinic receptors as non-competitive modulators (e.g., non-competitive antagonists), methods for their synthesis, methods for use, and their pharmaceutical compositions.Nicotinic receptors are targets for a great number of exogenous and endogenous compounds that allosterically modulate their function. See, Arias, H. R., Binding sites for exogenous and endogenous non-competitive inhibitors of the nicotinic acetylcholine receptor, 1376: 173-220 (1998) and Arias, H. R., Bhumireddy, P., Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors, & ...

Catalytic Hydrogenation for Producing Amines from Carboxylic Acid Amides, Carboxylic Acid Diamides, Di-, Tri-, or Polypeptides, or Peptide Amides

The present invention relates to a process for the preparation of amines, comprising the following steps: a. reaction of a (i) carboxylic acid amide of the general formula (I), or (ii) carboxylic acid diamide of the general formula (II), or (iii) di-, tri- or polypeptide, or (iv) peptide amide with carboxy-terminal amide function with an alkylating agent, b. addition of a hydrogenation catalyst to the reaction mixture in a molar ratio of from 1:10 to 1:100 000, based on carboxylic acid amide, carboxylic acid diamide, di-, tri- or polypeptide or peptide amide, c. reaction of the reaction mixture with hydrogen, where a hydrogen pressure of from 0.1 bar to 200 bar is established and where a temperature in a range of from 0° C. to 250° C. is established. 110-. (canceled)12. The process of claim 11 , wherein the alkylating agent is selected from the group consisting of: alkyl halides; esters of sulphonic acid; esters of fluorosulphonic acid; esters of trifluoromethanesulphonic acid; esters of chloroformic acid; oxonium salts; dialkyl sulphates; and diazomethane.13. The process of claim 11 , wherein the hydrogenation catalyst comprises at least one active metal.14. The process of claim 13 , wherein the active metal is a metal of group VII B and/or VIII B of the Periodic Table of the Elements.15. The process of claim 11 , wherein claim 11 , after step a) claim 11 , a base is added to the reaction mixture and wherein a molar ratio of base to alkylating agent of from 1:1 to 1:3 is produced.16. The process of claim 11 , wherein the reaction is carried out in a solvent.17. The process of claim 16 , wherein the solvent is selected from the group consisting of: hydrocarbons; chlorinated hydrocarbons; ethers; esters; and alcohols.18. The process of claim 11 , wherein the reaction is carried out without solvents.19. The process of claim 16 , wherein said alkylating agent is anhydrous and is selected from the group consisting of: carboxylic acid amide; carboxylic acid diamide; a di ...

ADENYLYL CYCLASE INHIBITORS FOR NEUROPATHIC AND INFLAMMATORY PAIN

The invention generally relates to adenylyl cyclase inhibitor compounds and methods for treating neuropathic or inflammatory pain by using those compounds. This application claims the benefit of and priority to U.S. Provisional Application No. 62/116,686, filed Feb. 16, 2015, which is incorporated by reference herein in its entirety.The invention generally relates to adenylyl cyclase inhibitors and methods of use thereof.Adenylyl cyclases are important mediators of signaling through G protein-coupled receptors. Adenylyl cyclase type 1 (AC1) belongs to a family of adenylyl cyclases that are stimulated by calcium in a calmodulin-dependent manner. Notably, AC1 is associated with chronic pain responses in several regions of the central nervous system. Accordingly, inhibition of AC1 has resulted in analgesic effects in both neuroinflammatory and neuropathic pain in rodent models. A dearth of AC1 inhibiting compounds and an inability to efficiently synthesize them means that their analgesic benefits cannot be widely realized and people continue to suffer from neuropathic and inflammatory pain.The invention generally relates to potent adenylyl cyclase inhibitor compounds. The invention further relates to methods for treating neuropathic or inflammatory pain by delivering adenylyl cyclase inhibitor compounds of the invention. Methods of the invention also provide for palladium-catalyzed γ-arylation of tertiary allylic amines and the synthesis of the disclosed AC1 inhibitor compounds as well as drug molecules such as naftifine, cinarizine, flunarizine, and analogs thereof. Heck arylation methods of the invention provide increased regio- and stereo-selectivity and yield over known methods.In certain aspects, the invention provides a compound of formula (I):wherein: X is carbon or nitrogen; n is 0 or 1; Ris selected from aryl, alkenyl, or alkyl optionally substituted by: aryl optionally substituted by halo, fused cycloalkenyl optionally substituted by halo, or fused ...

NICOTINIC ACETYLCHOLINE RECEPTOR SILENT AGONISTS

Derivatives of N,N-diethyl-N′-phenyl-piperazine, a silent agonist of the mammalian α7 nicotinic acetylcholine receptor, are provided. These silent agonists control the desensitization state of the receptor. Further provided are pharmaceutical compositions that allow the administration of the silent agonists of the disclosure to a subject animal or human in need of treatment for a pathological condition arising from such as inflammation. The novel silent agonists also may be co-administered to a patient simultaneously or consecutively with a type II positive allosteric modulator to modulate the activity of the receptor. 120-. (canceled)22. The compound of claim 21 , wherein R claim 21 , R claim 21 , and Ris each independently a hydrogen claim 21 , a methyl claim 21 , cyano claim 21 , methoxy claim 21 , a halogen claim 21 , trihaloalkyl claim 21 , a carboxamide claim 21 , pentafluorosulfanyl claim 21 , or hydroxyl.23. The compound of claim 21 , wherein R claim 21 , R claim 21 , and Ris each independently a hydrogen claim 21 , a methyl claim 21 , cyano claim 21 , methoxy claim 21 , a halogen claim 21 , a trihaloalkyl claim 21 , a carboxamide claim 21 , pentafluorosulfanyl claim 21 , or hydroxyl claim 21 , and Ris hydrogen.24. The compound of claim 21 , wherein:{'sub': 1', '2', '3, 'when Ris a methyl or a CN, Rand Rare each hydrogen;'}{'sub': 1', '2', '3, 'when Ris a methoxy, Ris hydrogen Ris hydrogen or methoxy;'}{'sub': 1', '2', '3, 'when Ris a halogen, Rand Rare each hydrogen;'}{'sub': 1', '2', '3, 'when Ris a trifluoromethyl, Rand Rare each hydrogen;'}{'sub': 1', '2', '3, 'when Ris a carboxamide, pentafluorosulfanyl, Rand Rare each hydrogen;'}{'sub': 1', '3', '2, 'when Rand Rare each hydrogen, Ris a methyl, a CN, a methoxy, a halogen, a trifluoromethyl, or a carboxamide, or OH; and'}{'sub': 1', '2', '3, 'when Rand Rare each hydrogen, Ris a methyl or Cl.'}26. The pharmaceutical composition of claim 25 , wherein R claim 25 , R claim 25 , and Ris each independently a ...

ORGANO-1-OXA-4-AZONIUM CYCLOHEXANE COMPOUNDS

Novel 1-oxa-4-azonium cyclohexane salts are described. These compounds can be used as structure directing agents, and they overcome many of the typical problems associated with OSDA synthesis and subsequent zeolite synthesis. Methods for synthesis of the 1-oxa-4-azonium cyclohexane salts from a variety of starting materials are also described. A substituted hydrocarbon is added to water to form a mixture, and a 1-oxa-4-azacyclohexane derivative is then added. The reaction mixture stirred until a solution containing the 1-oxa-4-azonium cyclohexane salt is obtained. 1. A morpholinium compound comprising a 1-oxa-4-azonium cyclohexane salt having a structure of:{'chemistry': {'@id': 'CHEM-US-00001', '@num': '00001', 'img': {'@id': 'EMI-C00001', '@he': '25.91mm', '@wi': '61.64mm', '@file': 'US20180265485A1-20180920-C00001.TIF', '@alt': 'embedded image', '@img-content': 'chem', '@img-format': 'tif'}}, 'br': None, 'sub': 1', '2', '3', '4', '9', '10', '5', '6', '7', '8, 'sup': +', '−, '2-R-2-R-3-R-3-R-4-R-4-R-5-R-5-R-6-R-6-R-1-oxa-4-azoniumcyclohexane-X,'}{'sub': 1', '8', 'n', '2n+1', '1', '8', '9', '10', 'm', '2m, 'wherein R-Rare independently selected from H or an alkyl group having the formula CHwhere n is in the range from 1 to 4; at least one of R-Ris an alkyl group; Rand Rform a cyclic alkyl group having the formula CHforming a heterocycle of ring size q, where m is in the range from 4 to 8, and q is in the range of 5 to m+1; X is hydroxide; and the total number of C atoms in the molecule is in a range of 8 to 17.'}2. The morpholinium compound of having the Formula 1 claim 1 , wherein at least two of R-Rare an alkyl group.3. The morpholinium compound of having the Formula 1 claim 1 , wherein at least two of R-Rare an alkyl group claim 1 , and wherein at least two of R-Rare the same alkyl group.4. The morpholinium compound of having the Formula 1 claim 1 , wherein the at least two of R-Rare Rand R claim 1 , or Rand R claim 1 , or Rand R claim 1 , or Rand R.5. A ...