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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 6815. Отображено 100.
23-08-2012 дата публикации

New compounds, pharmaceutical compositions and uses thereof

Номер: US20120214785A1
Автор: Bernd Nosse, Gerald Juergen Roth, Heike Neubauer, Joerg Kley, Martin Fleck, Niklas Heine, Thorsten Lehmann-Lintz
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to new compounds of the formula I to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

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Номер записи: 1
06-09-2012 дата публикации

Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer's disease, type 2 diabetes and parkinson's disease

Номер: US20120225890A1
Автор: Alan D. Snow, Beth Nguyen, Charlotte Coffen, David L. Coffen, David Larsen, Gerardo Castillo, Lesley Larsen, Rex T. Weavers, Stephen Lorimer, Thomas Lake, Virginia Sanders
Принадлежит: ProteoTech Inc

Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

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Номер записи: 2
04-10-2012 дата публикации

Pyridinecarboxamides, useful-plant-protecting composition comprising them and processes for their preparation and their use

Номер: US20120252670A1
Автор: Christopher Rosinger, Erwin Hacker, Frank Ziemer, Lothar Willms, Thomas Auler, Udo Bickers
Принадлежит: Individual

Compounds of the formula (I), or salts thereof, in which R 1 to R 4 are as defined in formula (I) of claim 1 are suitable as useful-plant-protecting agents for reducing or preventing harmful effects of agrochemicals on the useful plants and their method of preparation are described.

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Номер записи: 3
29-11-2012 дата публикации

Process of making alpha-aminooxyketone/alpha-aminooxyaldehyde and alpha-hydroxyketone/alpha-hydroxyaldehyde compounds and a process making reaction products from cyclic alpha, beta-unsaturated ketone substrates and nitroso substrates

Номер: US20120302792A1
Автор: Hiromi Torii, Hisashi Yamamoto, Norie Momiyama, Susumu Saito, Yuhei Yamamoto
Принадлежит: JAPAN SCIENCE AND TECHNOLOGY AGENCY

The present invention is directed to a process of making α-aminooxyketone and α-hydroxyketone compounds. The synthetic pathway generally involves reacting an aldehyde or ketone substrate and a nitroso substrate in the presence of a catalyst of the formula (IV): wherein X a -X c represent independently nitrogen, carbon, oxygen or sulfur and Z represents a 4 to 10-membered ring with or without a substituent and optionally a further step to convert the α-aminooxyketone compound formed to the α-hydroxyketone compound. The present invention results in α-aminooxyketone and α-hydroxyketone compounds with high enantioselectivity and high purity. The present invention is also directed to a catalytic asymmetric O-nitroso Aldol/Michael reaction. The substrates of this reaction are generally cyclic α,β-unsaturated ketone substrate and a nitroso substrate. This methodology generally involves reacting the cyclic α,β-unsaturated ketone substrate and the nitroso substrate in the presence of a proline-based catalyst, to provide a heterocyclic product.

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Номер записи: 4
25-04-2013 дата публикации

THIONATION PROCESS AND A THIONATING AGENT

Номер: US20130102774A1
Автор: Bergman Jan, Hasimbegovic Vedran, Pettersson Birgitta, Svensson Per H
Принадлежит: Vironova AB

A process for transforming a group >C═O (I) in a compound into a group >C═S (II) or into a tautomeric form of group (II) in a reaction giving a thionated reaction product, by use of crystalline PS.2 CHN as a thionating agent. A thionating agent which is crystalline PS.2 CHN. 1. A process for transforming a group >C═O (I) in a compound into a group >C═S (II) or into a tautomeric form of group (II) in a reaction giving a thionated reaction product , by use of crystalline PS.2 CHN as a thionating agent.2. A process according to claim 1 , wherein the thionating agent and the compound are allowed to react with each other in a liquid solvent medium for the compound and for the thionating agent.3. The process according to claim 1 , wherein the liquid solvent medium comprises pyridine claim 1 , a C1-C3 alkylnitrile claim 1 , a cyclic sulfone and/or a C1-C3 dialkylsulfone.4. The process according to claim 1 , wherein the liquid solvent medium comprises pyridine claim 1 , sulfolane claim 1 , dimethyl sulfone and/or acetonitrile.5. The process according to claim 1 , wherein the reaction is performed at a temperature of 60° C. to 180° C.6. The process according to claim 5 , wherein the reaction is performed at temperature of 115° C. to 175° C.7. The process according to claim 1 , wherein the compound comprises a group (I) that is present in an amide function.8. The process according to claim 1 , wherein the compound comprises a group (I) that is present in a ketone function.9. The process according to claim 1 , wherein the thionating agent is used at a molar ratio to the group (I) to be transformed of 1 mole PS.2 CHN per 1-4 moles of group (I).10. The process according to claim 1 , comprising separating the thionated reaction product from the reaction.11. The process according to claim 10 , wherein water is added to the reaction and the thionated reaction product is separated as a solid material claim 10 , by precipitation or crystallization.12. A thionating agent which is ...

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Номер записи: 5
02-05-2013 дата публикации

C7-Fluoro Substituted Tetracycline Compounds

Номер: US20130109657A1
Автор: Diana Katharine Hunt, Jingye Zhou, Louis Plamondon, Robert B. Zahler, Roger B. Clark, Xiao-Yi Xiao
Принадлежит: Tetraphase Pharmaceuticals Inc

The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

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Номер записи: 6
06-06-2013 дата публикации

Guanidine compound

Номер: US20130143860A1
Автор: Daisuke Suzuki, Hiroyoshi Yamada, Hisashi Mihara, Kousei Yoshihara, Norio Seki, Susumu Yamaki
Принадлежит: Astellas Pharma Inc

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

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Номер записи: 7
13-06-2013 дата публикации

CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS

Номер: US20130150367A1
Автор: Hornberger Wilfried, Hutchins Charles W., Jantos Katja, Kling Andreas, Mack Helmut, MOELLER Achim
Принадлежит:

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. 2. The carboxamide compound of claim 1 , in which A is C═O.3. The carboxamide compound of claim 1 , in which Q is CHor CHC.4. The carboxamide compound of claim 1 , in which Ris selected from:{'sub': 3', '10, 'sup': '1a', 'C-C-alkyl which is unsubstituted or may be partly or completely halogenated and/or have substituents R,'}{'sub': 1', '4', '1', '4, 'sup': '1c', 'phenyl-C-C-alkyl and hetaryl-C-C-alkyl, where phenyl and hetaryl in the last 2 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals R.'}5. The carboxamide compound of claim 1 , in which Ris phenyl claim 1 , which is unsubstituted or carries 1 claim 1 , 2 claim 1 , 3 or 4 identical or different radicals R.7. The carboxamide compound of claim 6 , in which X is C(O)—NH.8. The carboxamide compound of claim 6 , in which X is C(O)—NHR claim 6 , where Ris CN claim 6 , C-C-alkyl claim 6 , C-C-haloalkyl claim 6 , C-C-alkyl which has 1 claim 6 , 2 or 3 substituents R claim 6 , C-C-alkenyl claim 6 , C-C-alkynyl claim 6 , C-C-cycloalkyl claim 6 , C-C-cycloalkyl-C-C-alkyl claim 6 , C-C-heterocycloalkyl-C-C-alkyl claim 6 , C-C-alkoxy-C-C-alkyl claim 6 , aryl claim 6 , hetaryl claim 6 , aryl-C-C-alkyl or hetaryl-C-C-alkyl claim 6 , where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1 claim 6 , 2 or 3 substituents R.9. The carboxamide compound of claim 8 , in which Ris C-C-alkyl claim 8 , C-C-cycloalkyl claim 8 , phenyl-C-C-alkyl or hetaryl-C-C-alkyl claim 8 , where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1 claim 8 , 2 or 3 substituents Rand hetaryl is a 5- or 6- ...

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Номер записи: 8
27-06-2013 дата публикации

PRODUCTION METHOD OF INTERMEDIATE COMPOUND FOR SYNTHESIZING MEDICAMENT

Номер: US20130165659A1
Автор: An Ji Eun, KIM Bong Chan, Kim Kyu Young, Lee Hee Bong, Lee Kyu Woong
Принадлежит: LG LIFE SCIENCES LTD.

The present invention relates to a novel method for preparing a compound of formula (2) as the intermediate, which can be effectively used for preparation of a compound of formula (1) exhibiting good inhibitory activity against dipeptidyl peptidase IV enzyme. 3. The method according to claim 1 , wherein Pis t-butyl group claim 1 , and Pis methyl or ethyl group.4. The method according to claim 1 , wherein GO is triflate claim 1 , mesylate claim 1 , tosylate claim 1 , besylate or nonaflate.5. The method according to claim 1 , wherein R3 and R4 are hydrogen claim 1 , and R5 and R6 are fluorine.6. The method according to claim 2 , wherein in step (a) C-Ctrialkylamine is used as the base.7. The method according to claim 2 , wherein in step (b) acetic acid is used as the acid.8. The method according to claim 2 , wherein in the case of the compound of formula (2a) wherein Pis Boc and Pis t-butyl claim 2 , the hydrolysis of said step (c) is conducted under the basic condition to selectively remove only Pamong the protecting groups Pand Pto provide the compound of formula (2).9. The method according to claim 8 , wherein aqueous sodium hydroxide solution is used as the base.11. The method according to claim 10 , wherein in step (a) the reduction is conducted using NaBH.12. The method according to claim 10 , wherein in step (b) the Gcompound is selected from the group consisting of trifluoromethane sulfonic acid anhydride (TfO) claim 10 , trifluoromethane sulfonyl chloride (TfCl) claim 10 , methanesulfonyl chloride (MsCl) claim 10 , toluenesulfonyl chloride (TsCl) claim 10 , bromobenzenesulfonyl chloride (BsCl) claim 10 , (CF(CF)SO)F and (CF(CF)SO)O.14. The method according to claim 13 , wherein Pis Boc claim 13 , Pis i-propyl group or t-butyl group claim 13 , and GO is triflate or nonaflate.17. The method according to claim 16 , wherein Pis Boc claim 16 , and Pis i-propyl or t-butyl.18. The method according to claim 16 , wherein in step (a) chloroformate or BocO is used as ...

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Номер записи: 9
04-07-2013 дата публикации

SUBSTITUTED ANILINES AS CCR(4) ANTAGONISTS

Номер: US20130172315A1
Автор: Charvat Trevor T., Fan Junfa, Lange Christorpher W., LELETI Manmohan Reddy, Li Yandong, MacMahon Jeffrey P., Mali Venkat Reddy, Powers Jay, Punna Sreenivas, Yang Ju
Принадлежит: ChemoCentryx, Inc.

Aniline compounds are provided which bind to CCR(4) and are useful for the treatment of diseases such as allergic diseases, autoimmune diseases, graft rejection and cancer. 2. A compound of claim 1 , wherein X and Y are not both N.3. A compound of claim 1 , wherein Ris H claim 1 , and each Ris a member independently selected from the group consisting of Calkyl claim 1 , Chaloalkyl claim 1 , halogen and —CN.5. A compound of claim 4 , wherein X is C or CH.8. A compound of claim 7 , wherein n is 1 claim 7 , and Ris hydrogen or methyl.10. A compound of claim 9 , wherein n is 1 claim 9 , and Ris hydrogen or methyl.12. A compound of claim 11 , wherein n is 1 claim 11 , and Ris hydrogen or methyl.14. A compound of claim 1 , wherein B is C(O).15. A compound of claim 1 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidine and piperidine.16. A compound of claim 1 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-2-yl and piperidin-2-yl claim 1 , and at least one of R claim 1 , Rand Ris other than hydrogen.17. A compound of claim 1 , wherein B is a bond.18. A compound of claim 1 , wherein B is a bond and the ring having Z as a ring vertex is selected from the group consisting of pyrrolidine claim 1 , piperidine and cyclohexane.19. A compound of claim 1 , wherein B is a bond and the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl claim 1 , pyrrolidin-2-yl claim 1 , piperidin-1-yl claim 1 , piperidin-2-yl claim 1 , piperidin-3-yl and cyclohexane.20. A compound of claim 1 , wherein B is a bond and the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl claim 1 , pyrrolidin-2-yl claim 1 , piperidin-1-yl claim 1 , piperidin-2-yl claim 1 , piperidin-3-yl and cyclohexane; and at least one of R claim 1 , Rand Ris other than hydrogen.21. A compound of claim 1 , wherein Z is CH or N.23. A pharmaceutical composition ...

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Номер записи: 10
04-07-2013 дата публикации

ANTI-INFLAMMATORY AGENTS

Номер: US20130172318A1
Автор: Fox David John, Grainger David John
Принадлежит:

Disclosed herein are methods of preventing or treating inflammatory diseases using 3-aminolactam compounds, each with aromatic “tail groups”. Compounds as defined by formulae (I) and (I′), and the medical uses of the compounds, are described herein. 3. (canceled)4. (canceled)6. A compound of{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, ','}provided that the compound is not selected from the group consisting of: (S)-3-(4′-methoxybenzoylamino)-caprolactam, (S)-3-(4′-methylbenzoylamino)-caprolactam, (S)-3-(3′-trifluoromethylbenzoylamino)-caprolactam, (S)-3-(2′-carboxybenzoyl-amino)-caprolactam, and (S)-3-(3′,4′,5′-trimethoxybenzoylamino)-caprolactam.7. A pharmaceutical composition comprising claim 5 , as active ingredient claim 5 , a compound as defined in claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , and at least one pharmaceutically acceptable excipient and/or carrier.8. The compound according to claim 1 , wherein n=2.9. The compound according to claim 1 , wherein n=3.10. The compound according to claim 1 , wherein X is haloalkyl.11. The compound according to claim 2 , wherein the compound is selected from the group consisting of:(S)-3-(4′-methylbenzoylamino)-caprolactam, and(S)-3-(3′,5′-dimethylbenzoylamino)-caprolactam,and pharmaceutically acceptable salts thereof.12. A compound according to claim 2 , selected from the group consisting of:(S)-3-fluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2-fluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-4-fluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)—N-(2-oxopiperidin-3-yl)-4-(trifluoromethyl)benzamide,(S)—N-(2-oxopiperidin-3-yl)-3-(trifluoromethyl)benzamide,(S)—N-(2-oxopiperidin-3-yl)-2-(trifluoromethyl)benzamide,(S)-2,3-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2,4-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2,5-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2,6-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-3,4-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-3,5-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-3 ...

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Номер записи: 11
04-07-2013 дата публикации

Alpha-AminoCycloLactam Ligands for G-Protein Coupled Receptors, and Methods of Using Same

Номер: US20130172319A1
Автор: Fox David John, Grainger David J.
Принадлежит:

The invention relates to the generation of a library of compounds enriched in agonist and antagonists for members of the G-protein coupled class of receptors (GPCRs). 4. A library composed of claim 1 , or enriched in claim 1 , library elements which are compounds according to .5. A method of screening in an assay claim 4 , a library according to claim 4 , to identify agent(s) which modulate signalling through GPCRs.6. The method according to claim 5 , wherein the agent(s) identified are antagonists at one or more GPCRs.7. The method according to claim 5 , wherein the agent(s) identified are agonists at one or more GPCRs.8. The method according to claim 5 , wherein the GPCR is selected from the group consisting of adrenalin receptors claim 5 , endothelin receptors claim 5 , chemokine receptors claim 5 , EDG receptors claim 5 , VIP/PECAP receptors claim 5 , dopamine receptors claim 5 , serotonin receptors claim 5 , purine receptors claim 5 , metabotropic glutamate receptors claim 5 , acetyl choline receptors claim 5 , C5a receptors claim 5 , fMLP receptors claim 5 , glucagon or GLP receptors claim 5 , NPY receptors claim 5 , MSH receptors claim 5 , glycoprotein hormone receptors claim 5 , protease activated receptors (PARs) claim 5 , somatostatin receptors claim 5 , angiotensin receptors claim 5 , cholecystokinin receptors claim 5 , and melatonin receptors. This application is a continuation of application Ser. No. 13/193,274, now U.S. Pat. No. 8,389,279, which is a continuation of application Ser. No. 11/574,656, now U.S. Pat. No. 8,008,289, which is the U.S. national stage of PCT/GB2005/003134, filed Aug. 10, 2005 and published in English as WO 2006/024815 A1 on Mar. 9, 2006, which claims the benefit of priority under 35 U.S.C. §119 to United Kingdom application serial no. 0419517.8, filed Sep. 2, 2004, all of which applications and publications are incorporated herein by reference.The invention relates to the generation of a library of compounds enriched in agonist ...

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Номер записи: 12
18-07-2013 дата публикации

PIPERIDINYL-SUBSTITUTED LACTAMS AS GPR119 MODULATORS

Номер: US20130184257A1
Автор: Aicher Thomas Daniel, Bencsik Josef R., Boyd Steven Armen, Condroski Kevin Ronald, Fell Jay Bradford, Fischer John P., Hinklin Ronald Jay, Pratt Scott Alan
Принадлежит:

Compounds of Formula (I) and pharmaceutically acceptable salts thereof in which X, X, L, R, R, R, Rand n have the meanings given in the specification, are modulators of GPR119 and are useful in the treatment or prevention of diseases such as such as, but not limited to, type 2 diabetes, diabetic complications, symptoms of diabetes, metabolic syndrome, obesity, dyslipidemia, and related conditions. 2. The compound according to claim 1 , wherein:{'sup': 1', '1, 'Xis CR;'}{'sup': 2', '2, 'Xis CR; and'}{'sup': 1', '2', '3', '4, 'sub': '3', 'R, R, Rand Rare independently selected from H, (1-6C)alkyl, CFand halogen.'}3. The compound of claim 2 , wherein:{'sup': 1', '2, 'Rand Rare independently selected from H, F and Cl; and'}{'sup': 3', '4, 'sub': '3', 'Rand Rare independently selected from H, Me, F, Cl and CF.'}4. The compound of claim 3 , wherein:{'sup': 1', '3, 'Rand Rare F; and'}{'sup': 2', '4, 'Rand Rare H.'}5. The compound of claim 3 , wherein:{'sup': 1', '4, 'Rand Rare H; and'}{'sup': 2', '3, 'Rand Rare F.'}6. The compound of claim 3 , wherein:{'sup': 1', '2', '4, 'R, Rand Rare H; and'}{'sup': '3', 'Ris F.'}7. The compound according to claim 1 , wherein:{'sup': '1', 'Xis N; and'}{'sup': 2', '2, 'Xis CR.'}8. The compound of claim 7 , wherein R claim 7 , Rand Rare independently selected from H claim 7 , halogen claim 7 , and (1-6C)alkyl.9. The compound of claim 8 , wherein R claim 8 , Rand Rare each H.10. The compound of claim 8 , wherein Rand Rare H and Ris Cl or F.11. The compound according to claim 1 , wherein:{'sup': 1', '1, 'Xis CR; and'}{'sup': '2', 'Xis N.'}12. The compound according to claim 11 , wherein R claim 11 , Rand Rare independently selected from H claim 11 , halogen claim 11 , and (1-6C)alkyl.13. The compound according to claim 12 , wherein each of R claim 12 , Rand Ris H.14. The compound according to claim 12 , wherein Rand Rare H and Ris Cl or F.15. The compound according to claim 1 , wherein Ris selected from (1-3C alkyl)sulfonyl claim 1 , (3-6C ...

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Номер записи: 13
25-07-2013 дата публикации

APOPTOSIS PROMOTERS

Номер: US20130190488A1
Автор: Bruncko Milan, Ding Hong, Elmore Steven, Kunzer Aaron, Lynch Christopher L., McClellan William, Mitten Michael, Park Cheol-Min, Petros Andrew, Shoemaker Alexander, Song Xiaohong, Tu Noah, Wang Xilu, WENDT Michael
Принадлежит: ABBOTT LABORATORIES

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member. 19-. (canceled)10. A compound , or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(2,4-dimenthyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;4-(((1R)-3-(bis(2-methoxyethyl)amino)-1 ...

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Номер записи: 14
08-08-2013 дата публикации

ANTI-INFLAMMATORY AGENTS

Номер: US20130203734A1
Автор: Fox David John, Grainger David John
Принадлежит:

Disclosed herein are methods of preventing or treating inflammatory diseases using sulfonamide analogs of 3-aminolactam compounds, each with aromatic “tail groups”. Compounds as defined by formulae (I) and (I′), and the medical uses of the compounds, are described herein. 3. (canceled)4. (canceled)5. A compound according to claim 1 , with the proviso that:{'sub': 2', '6', '1', '7', '1', '7, 'when n =3, then at least one of C-Con the phenyl ring is substituted with a group other than halogen, C-Calkyl, or C-Chaloalkyl; and'}when n =1, 2 or 3, then{'sub': 2', '6, 'Cor Con the phenyl ring are other than hydrogen or fluorine, or'}{'sub': 3', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl,'}{'sub': 1', '6', '1', '6, 'C-Calkoxy, or C-Chaloalkyl, or'}{'sub': 4', '1', '6', '1', '6', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl, C-Calkoxy, C-Chaloalkyl, amino, aminoalkyl or aminodialkyl, or'}{'sub': '5', 'Con the phenyl ring is other than hydrogen or halogen;'}provided that the compound is neither of:3-(2′-carboxybenzenesulfonylamino)-tetrahydropyridin-2-one, and (R)-3-(4′-methylbenzenesulfonylamino)-caprolactam.6. A compound of claim 2 , with the proviso that:{'sub': 2', '6', '1', '7', '1', '7, 'when n=3, then at least one of C-Con the phenyl ring is substituted with a group other than halogen, C-Calkyl, or C-Chaloalkyl; and'}when n =1, 2 or 3, then{'sub': 2', '6, 'Cor Con the phenyl ring are other than hydrogen or fluorine, or'}{'sub': 3', '1', '6', '1', '6', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl, C-Calkoxy, or C-Chaloalkyl, or'}{'sub': 4', '1', '6', '1', '6', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl, C-Calkoxy, C-Chaloalkyl, amino, aminoalkyl or aminodialkyl, or'}{'sub': '5', 'Con the phenyl ring is other than hydrogen or halogen;'}provided that the compound is not one of the group consisting of:(S)-3-(4′-methylbenzenesulfonylamino)-tetrahydropyridin-2-one ...

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Номер записи: 15
08-08-2013 дата публикации

CYTOKINE INHIBITORS

Номер: US20130203815A1
Автор: Bandgar Babasaheb Pandurang, Totre Jalindar Vasant
Принадлежит: Piramal Enterprises Limited

The present invention provides compounds represented by general formula (I): 2. The compound of formula (I) according to claim 1 , wherein{'sub': '1', 'Ris selected from hydrogen or alkyl;'}{'sub': '2', 'Rat each occurrence is independently selected from hydrogen, halogen, hydroxy, alkyl or alkoxy; and'}T is phenyl; which is unsubstituted or substituted by at least one group selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, carboxy, amino, nitro or cyano;or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.6. The compound of formula (I) according to claim 1 , wherein{'sub': '1', 'Ris selected from hydrogen or alkyl;'}{'sub': '2', 'Rat each occurrence is independently selected from hydrogen, halogen, hydroxy, alkyl or alkoxy; and'}T is 5 or 6 membered heteroaryl; wherein the heteroaryl is unsubstituted or substituted by at least one group selected from; halogen, hydroxy, alkyl, haloalkyl, alkoxy, carboxy, amino, nitro or cyano;or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.14. The compound of formula (I) according to claim 1 , wherein the compound is:(+/−)3-(2-Chlorophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one hydrochloride,(−)3-(2-Chlorophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+)3-(2-Chlorophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+/−)3-(3-Bromophenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+/−)3-(2,4-Dimethoxy-phenyl)-1-(2-hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)prop-2-en-1-one,(+/−)1-(2-Hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxyphenyl)-3-m-tolylprop-2-en-1-one,(+/−)1-(2-Hydroxy-3-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4,6-dimethoxy-phenyl)-3-o-tolylprop-2-en-1-one,(+/−)1-(2-Hydroxy-3-(2-(hydroxymethyl ...

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Номер записи: 16
29-08-2013 дата публикации

NOVEL HETEROCYCLIC DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (AS AMENDED)

Номер: US20130225596A1
Автор: Asahi Kentaro, Endoh Takeshi, Horiguchi Tohru, Jikihara Sae, Kai Hiroyuki
Принадлежит:

The present invention provides novel compounds having a P2Xand/or P2Xreceptor antagonistic effect. 2. The pharmaceutical composition having a P2Xand/or P2Xreceptor antagonistic effect according to claim 1 , comprising the compound wherein ring A is a substituted or unsubstituted cyclohexane ring claim 1 , a substituted or unsubstituted cyclohexadiene ring claim 1 , a substituted or unsubstituted cyclohexene ring claim 1 , a substituted or unsubstituted benzene ring claim 1 , a substituted or unsubstituted pyridine ring claim 1 , a substituted or unsubstituted dihydropyridine ring claim 1 , a substituted or unsubstituted tetrahydropyridine ring claim 1 , a substituted or unsubstituted pyrimidine ring claim 1 , a substituted or unsubstituted dihydropyrimidine ring claim 1 , a substituted or unsubstituted tetrahydropyrimidine ring claim 1 , a substituted or unsubstituted hexahydropyrimidine ring claim 1 , a substituted or unsubstituted piperidine ring claim 1 , a substituted or unsubstituted piperazine ring claim 1 , a substituted or unsubstituted pyrazine ring claim 1 , a substituted or unsubstituted dihydropyrazine ring claim 1 , a substituted or unsubstituted tetrahydropyrazine ring claim 1 , a substituted or unsubstituted pyridazine ring claim 1 , a substituted or unsubstituted dihydropyridazine ring claim 1 , a substituted or unsubstituted tetrahydropyridazine ring claim 1 , a substituted or unsubstituted indene ring claim 1 , a substituted or unsubstituted benzofuran ring claim 1 , a substituted or unsubstituted benzofuran ring claim 1 , a substituted or unsubstituted benzo(b)thiophene ring claim 1 , a substituted or unsubstituted benzo(c)thiophene ring claim 1 , a substituted or unsubstituted indoline ring claim 1 , a substituted or unsubstituted indole ring claim 1 , a substituted or unsubstituted benzimidazole ring claim 1 , a substituted or unsubstituted cyclopenta[b]pyridine ring claim 1 , a substituted or unsubstituted 1H-indazole ring claim 1 , a ...

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Номер записи: 17
29-08-2013 дата публикации

Method To Prepare beta-Functionalized Aliphatic Esters

Номер: US20130225852A1
Автор: Dominik Ohlmann, Lukas J. Goossen, Markus Dierker
Принадлежит: Cognis IP Management GmbH

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

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Номер записи: 18
17-10-2013 дата публикации

BETA-LACTAMASE INHIBITORS

Номер: US20130274475A1
Автор: Mangion Ian, Rivera Nelo, Ruck Rebecca T., Shelvin Michael
Принадлежит:

Substituted bicyclic beta-lactams of Formula I: 2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein bond a is a single bond and X is —CH— or —CHCH—.3. The compound according to or claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OSOM.4. The compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris OSOH.5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C(O)N(R)R.6. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris HetA claim 5 , CH-HetA claim 5 , CHCH-HetA claim 5 , CH(CH)-HetA claim 5 , or CH(CHOH)-HetA.7. The compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein HetA is an optionally fused claim 6 , saturated heterocyclic ring selected from the group consisting of azetidinyl claim 6 , pyrrolidinyl claim 6 , oxopyrrolidinyl claim 6 , piperidinyl claim 6 , piperazinyl claim 6 , tetrahydropyranyl claim 6 , tetrahydrothiopyranyl claim 6 , morpholinyl claim 6 , 1 claim 6 ,1-dioxidotetrahydrothiopyranyl claim 6 , azepanyl claim 6 , oxazepanyl claim 6 , azocanyl claim 6 , and azabicyclo[3.1.0]cyclohexyl claim 6 , wherein the heterocyclic is optionally substituted with 1 or 2 (CH)N(R)Rand optionally substituted with 1 or 2 (CH)R.9. The compound according to claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein T is H claim 8 , CH claim 8 , pyrrolidin-3-yl claim 8 , piperidin-4-yl claim 8 , (CH)OCH claim 8 , (CH)OH claim 8 , (CH)F claim 8 , (CH)-piperidinyl claim 8 , (CH)-pyrrolidinyl; and T′ is H claim 8 , F claim 8 , O—Calkyl claim 8 , OH claim 8 , NH claim 8 , N(H)CH claim 8 , N(CH).10. The compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris HetB.11. The compound according to claim 12 , or a pharmaceutically acceptable salt thereof ...

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Номер записи: 19
31-10-2013 дата публикации

Psyllid Attractants and Their Uses

Номер: US20130287727A1
Автор: Dimitratos Spiros, Woods Daniel F.
Принадлежит: Inscent, Inc.

The present specification discloses psyllid attractants, compositions comprising such attractants, lures, traps and other devices using such attractants, methods and uses to attract, capture and/or kill psyllids using such attractants, compositions and/or lures, traps and/or other devices, and methods and uses for monitoring a psyllid population using such attractants, compositions and/or lures, traps and/or other devices. 156-. (canceled)62. The compound of claim 57 , wherein the compound has a binding affinity for a psyllid OBP or SAP having an equilibrium dissociation constant of less than 0.500 nM claim 57 , less than 0.450 nM claim 57 , less than 0.400 nM claim 57 , less than 0.350 nM claim 57 , less than 0.300 nM claim 57 , less than 0.250 nM claim 57 , less than 0.200 nM claim 57 , less than 0.150 nM claim 57 , less than 0.100 nM claim 57 , or less than 0.050 nM.63. A composition comprising one or more of the compounds as defined in .64. The composition of claim 57 , wherein the composition is a liquid composition claim 57 , a semi-solid composition claim 57 , or a solid composition.65. A device comprising one or more of the compounds as defined in .66. A method of capturing psyllids claim 57 , the method comprising using one or more of the compounds as defined in to attract the psyllids to a device claim 57 , thereby capturing the psyllids.67. A method of killing psyllids claim 57 , the method comprising using one or more of the compounds as defined in to attract the psyllids to a device claim 57 , thereby killing the psyllids.68. A method of monitoring a psyllid population claim 57 , the method comprising a) using one or more of the compounds as defined in to attract psyllids to a device claim 57 , thereby capturing the psyllids; b) counting the psyllids to determine a number of captured psyllids; and c) performing a statistical analysis on the number of captured psyllids in order to determine the psyllid population claim 57 , thereby monitoring the psyllid ...

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Номер записи: 20
14-11-2013 дата публикации

Thionating agent

Номер: US20130303767A1
Автор: Birgitta Pettersson, Jan Bergman, Per H Svensson, Vedran Hasimbegovic
Принадлежит: Vironova AB

A process for transforming a group >C═O (I) in a compound into a group >C═S (II) or into a tautomeric form of group (II) in a reaction giving a thionated reaction product, by use of crystalline P 2 S 5 .2 C 5 H 5 N as a thionating agent. A thionating agent which is crystalline P 2 S 5 .2 C 5 H 5 N.

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Номер записи: 21
21-11-2013 дата публикации

Alpha, beta-unsaturated imines

Номер: US20130310254A1
Автор: Ebbinghaus-Kintscher Ulrich, GÖRGENS Ulrich, Horstmann Sebastian, Maue Michael, Schwarz Hans-Georg, Turberg Andreas, Velten Robert, VOERSTE Arnd, Werner Stefan
Принадлежит: Bayer Intellectual Property GmbH

The present application relates to novel alpha, beta-unsaturated imines, to processes for their preparation, to their use for controlling animal pests including arthropods and in particular insects and to their use in the control of vectors. 2. The compound according to claim 1 , where Arepresents —C(R claim 1 ,R)—.3. The compound according to claim 1 , where Arepresents a —C(R claim 1 ,R)— group and where{'sup': 2', '3, 'said C(R,R)— group forms a double bond with the adjacent B position, or'}{'sup': 2', '3', '1', '2', '1', '2, 'sub': 'n', 'said C(R,R)— group is a bridging group which, together with a further bridging group and any B groups, located between these bridging groups, of the C(═C(W,X-Q)-C(═N-Q)-A-[B]-Aring and a corresponding bridge U forms an unsubstituted or substituted cyclic system, or'}{'sup': 2', '3, 'this said C(R,R)— group carries a substituent V.'}4. The compound according to claim 1 , where Ais part of a cyclic system.5. The compound according to claim 1 , where Ais part of a carbocyclic system comprising 6 ring atoms or part of a 5- or 6-membered heterocyclic system.6. The compound according to claim 5 , where Ais part of an aromatic system comprising 6 ring atoms or part of a 5- or 6-membered heteroaromatic system.7. The compound according to claim 1 , where n is 2.11. An insecticidal composition claim 1 , wherein said insecticidal composition comprises at least one compound according to claim 1 , and an extender and/or surfactant.12. A method for protecting transgenic and/or conventional seed and a plant generated therefrom against attack by pests claim 1 , comprising treating the seed with at least one compound according to .13. A compound according claim 1 , capable of being used for controlling pests.14. A compound according to claim 1 , capable of being used for controlling vectors.15. A seed in which a compound according to claim 1 , has been applied to said seed as a constituent of a casing and/or as a further layer and/or further ...

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Номер записи: 22
19-12-2013 дата публикации

VINYL-ARYL DERIVATIVES FOR INFLAMMATION AND IMMUNE-RELATED USES

Номер: US20130338163A1
Автор: Chen Shoujun
Принадлежит: Synta Phamaceuticals Corp.

The invention relates to compounds that are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders. 2. The compound of claim 1 , wherein Y is substituted with one to two substituents.3. The compound of claim 2 , wherein the one to two substituents are each independently a lower alkyl or a halo.4. The compound of claim 3 , wherein Y is a difluorophenyl.5. The compound of claim 4 , wherein Y is 2 claim 4 ,6-difluorophenyl.6. The compound of claim 1 , wherein L is —NHCH— claim 1 , —CHNH— claim 1 , —NH—C(O)— claim 1 , or —C(O)—NH—.7. The compound of claim 6 , wherein L is —NHC(O)—.8. The compound of claim 1 , wherein Ris selected from the group consisting of a halo claim 1 , an optionally substituted alkyl claim 1 , an optionally substituted alkenyl claim 1 , an optionally substituted alkynyl claim 1 , an optionally substituted cycloalkyl claim 1 , an optionally substituted cycloalkenyl claim 1 , an optionally substituted heterocyclyl claim 1 , an optionally substituted aryl claim 1 , an optionally substituted heteroaryl claim 1 , an optionally substituted aralkyl claim 1 , and an optionally substituted heteraralkyl.9. The compound of claim 8 , wherein Ris selected from the group consisting of halo claim 8 , and an optionally substituted lower alkyl.10. The compound of claim 1 , wherein Xis CHand Xis NR.11. The compound of claim 1 , wherein Xis CHand Xis NR.12. The compound of claim 1 , wherein Xand Xare both CH or both N.13. (canceled)14. The compound of claim 1 , wherein Xis N and Xis CH.15. (canceled)16. The compound of claim 1 , whereinY is a difluorophenyl;L is —NHC(O)—;{'sub': '1', 'Ris selected from the group consisting of halo and an optionally substituted lower alkyl; and'}m is 0.1830-. (canceled)3247-. (canceled)4959-. (canceled)6176-. (canceled)77. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable carrier and a compound of .78. The pharmaceutical ...

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Номер записи: 23
09-01-2014 дата публикации

PIPERIDINONE DERIVATIVES AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER

Номер: US20140011796A1
Автор: BARTBERGER Michael David, BECK Hilary Plake, Chen Xiaoqi, Connors Richard Victor, Deignan Jeffrey, Duquette Jason, Eksterwicz John, FISHER BENJAMIN, Fox Brian Matthew, FU Jiasheng, FU Zice, GONZALEZ BUENROSTRO Ana, Gonzalez Lopez De Turiso Felix, Gribble Michael William, Gustin Dann James, HEATH Julie Anne, HUANG Xin, JIAO XianYun, Johnson Michael, KAYSER Frank, Kopecky David John, LAI SuJen, LI Yihong, LI Zhihong, Liu Jiwen, LOW Jonathan Dante, Lucas Brian Stuart, Ma Zhihua, McGee Lawrence R., McIntosh Joel, McMinn Dustin, Medina Julio Cesar, Mihalic Jeffrey Thomas, Olson Steven Howard, REW Yosup, Roveto Philip Marley, SUN Daqing, Wang Xiaodong, WANG Yingcai, YAN Xuelei, Yu Ming, ZHU Jiang
Принадлежит: Amgen Inc.

The present invention provides MDM inhibitor compounds of Formula I, 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —C(H)RR claim 1 , —NRR claim 1 , phenyl or pyridine claim 1 , wherein the phenyl or the pyridyl substituted with one or more Rx as allowed by valence.12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof claim 11 , wherein Re is H or methyl or ethyl.14. The compound of claim 13 , or a pharmaceutically acceptable salt thereof claim 13 , wherein Re is H or methyl or ethyl.19. A compound claim 13 , or a pharmaceutically acceptable salt thereof claim 13 , selected from:2-((3R,5R,6S)-1-((S)-1-tert-butoxy-1-oxobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)acetic acid;2-((3S,5R,6S)-1-((S)-1-tert-butoxy-1-oxobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-1-oxobutan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-4-methyl-1-oxopentan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-1-oxopentan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3S,5S,6R)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((R)-1-ethoxy-1-oxopentan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-1-((S)-2-tert-Butoxy-1-cyclopropyl-2-oxoethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-cyclopropyl-2-hydroxyethyl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-methoxybutan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5 ...

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Номер записи: 24
23-01-2014 дата публикации

Compounds, Compositions, and Methods for Cancer Therapy

Номер: US20140024639A1
Автор: Adams Drew, Boskovic Zarko, Dai Mingji, Hussain Mahmud Mustaqim, Schreiber Stuart
Принадлежит:

Compounds including various oligomers of piperlongumine and/or piperlongumine analogues as well as certain piperlongumine analogues that exhibit improved toxicity to cancer cells are disclosed. Also provided are compositions that comprise the compounds, methods of making compositions comprising the compounds, methods of making the compounds, and the use of compounds in methods for treating cancer. 3. The compound of claim 1 , wherein Ris a C≡C-cycloalkyl group wherein said cycloalkyl is a C3 to C6 ring and/or wherein Ris hydrogen or a thienyl group.4. The compound of claim 3 , wherein Ris a C≡C-cycloalkyl claim 3 , wherein said cycloakyl is substituted at the ring carbon that is bound to the alkynyl carbon with a hydroxyl group and/or wherein Ris hydrogen or a thienyl group.5. The compound of claim 1 , wherein Ris a C≡C-phenyl or a C≡C-phenyl halide wherein the halide is substituted ortho or para to the phenyl ring carbon that is bound to the alkynyl carbon and/or wherein Ris hydrogen or a thienyl group.6. The compound of claim 2 , wherein Rand Rare independently selected from a group consisting of hydrogen claim 2 , a halogen claim 2 , and a C≡C-cycloalkyl group wherein said cycloalkyl is a C3 to C6 ring and/or wherein Rand R11 are independently selected from a group consisting of hydrogen and a thienyl group.7. The compound of claim 6 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 6 , a halogen claim 6 , and a C≡C-cycloalkyl group claim 6 , wherein said cycloakyl is substituted at the ring carbon that is bound to the alkynyl carbon with a hydroxyl group and/or wherein Ris hydrogen or a thienyl group.8. The compound of claim 2 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 2 , a halogen claim 2 , and is a C≡C-phenyl or a C≡C-phenyl halide wherein the halide is substituted ortho or para to the phenyl ring carbon that is bound to the alkynyl carbon and/or wherein Ris hydrogen or a thienyl ...

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Номер записи: 25
23-01-2014 дата публикации

Small molecule inhibitors of necroptosis

Номер: US20140024657A1
Автор: Emily S. Hsu, Junying Yuan
Принадлежит: Harvard College

The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I)-(VIII) and by Compounds (1)-(7), (13)-(26), (27)-(33), (48)-(57), and (58)-(70). These necrostatins are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring necrostatins. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

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Номер записи: 26
06-02-2014 дата публикации

Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer's disease, type 2 diabetes, and parkinson's disease

Номер: US20140038980A1
Автор: Alan D. Snow, Beth Nguyen, Gerardo Castillo, Thomas Lake, Virginia Sanders
Принадлежит: ProteoTech Inc

Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

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Номер записи: 27
03-04-2014 дата публикации

QUINONE COMPOUNDS FOR TREATING APE1 MEDIATED DISEASES

Номер: US20140094464A1
Автор: KELLEY Mark R., Wikel James H.
Принадлежит: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

The invention described herein pertains to compounds and compositions for treating Ape1 mediated diseases. In particular, the invention described herein pertains to quinone compounds and pharmaceutical compositions containing them for treating Ape1 mediated diseases. 2. The compound of wherein each Ris alkoxy.3. The compound of wherein Rrepresents optionally substituted benzo.4. (canceled)5. The compound of wherein R is alkyl or heteroalkyl claim 1 , each of which is optionally substituted.6. The compound of wherein R is optionally substituted alkyl.7. (canceled)8. The compound of wherein R is alkoxy.9. The compound of wherein R is alkylthio.10. The compound of wherein R is halo.11. The compound of wherein each Ris optionally substituted alkyl.12. (canceled)13. The compound of wherein one Ris polyhydroxyalkyl.14. The compound of wherein both Rare taken together with the attached nitrogen to form an optionally substituted heterocycle selected from the group consisting of pyrrolidine claim 1 , piperidine claim 1 , piperazine claim 1 , morpholine claim 1 , pyrrolidinone claim 1 , piperidinone claim 1 , piperazinone claim 1 , and morpholinone.15. (canceled)16. The compound of wherein at least one Ris hydrogen.17. The compound of wherein at least one Ris alkyl.18. The compound of wherein both Rare alkyl.19. The compound of wherein both Rare taken together with the attached nitrogen and oxygen to form an optionally substituted heterocycle selected from the group consisting of oxazolidine claim 1 , oxazine claim 1 , oxazapine claim 1 , oxazolidinone claim 1 , oxazinone claim 1 , and oxazapinone.20. The compound of wherein X is optionally substituted alkylene.21. The compound of wherein X is an epoxy alkylene.22. The compound of wherein X is optionally substituted alkenylene.2324-. (canceled)25. A pharmaceutical composition comprising one or more compounds of .2627-. (canceled)28. A method for treating a disease responsive to Ape1 inhibition in a host animal claim 1 , the ...

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Номер записи: 28
10-04-2014 дата публикации

Guanidine compound

Номер: US20140100210A1
Автор: Daisuke Suzuki, Hiroyoshi Yamada, Hisashi Mihara, Kousei Yoshihara, Norio Seki, Susumu Yamaki
Принадлежит: Astellas Pharma Inc

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

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Номер записи: 29
03-01-2019 дата публикации

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

Номер: US20190002398A1
Автор: Clark Roger B., Hunt Diana K., Plamondon Louis, Shanghai Jingye, Xiao Xiao-Yi, Zahler Robert
Принадлежит:

The present invention is directed to a compound represented by Structural Formula (A): 4. The compound of claim 3 , wherein Ris hydrogen or a (C-C)alkyl.5. The compound of claim 3 , wherein Ris selected from (C-C)alkyl claim 3 , (C-C)cycloalkyl(C-C)alkyl claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , phenyl claim 3 , phenyl(C-C)alkyl claim 3 , (C-C)cycloalkyl and halo(C-C)alkyl claim 3 , wherein each alkyl claim 3 , alkoxy and cycloalkyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl and halo; and each phenyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl claim 3 , halo claim 3 , (C-C)alkoxy claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , —CN claim 3 , halo(C-C)alkyl claim 3 , and halo(C-C)alkoxy.6. The compound of any one of claim 3 , wherein Ris selected from hydrogen claim 3 , methyl and ethyl.7. The compound of claim 6 , wherein Ris selected from the group consisting of cyclopropyl claim 6 , cyclobutyl claim 6 , cyclopentyl claim 6 , cyclopropylmethyl claim 6 , cyclobutylmethyl claim 6 , phenyl claim 6 , benzyl claim 6 , —(CH)—O—CH claim 6 , —(CH)—OCH claim 6 , —C(CH) claim 6 , —CH(CH) claim 6 , —CHC(CH) claim 6 , —CHCH(CH) claim 6 , —CH—CF claim 6 , —(CH)—CHF claim 6 , and —(CH)CH; n is 0 claim 6 , 1 claim 6 , 2 claim 6 , 3 claim 6 , 4 claim 6 , 5 or 6; and wherein the phenyl or benzyl group represented by Ris optionally substituted with one or two substituents independently selected from the group consisting of (C-C)alkyl claim 6 , halogen claim 6 , (C-C)alkoxy claim 6 , (C-C)alkoxy(C-C)alkyl claim 6 , —CN claim 6 , halo(C-C)alkyl claim 6 , and halo(C-C)alkoxy.8. The compound of claim 7 , wherein Ris selected from cyclopropyl claim 7 , cyclopropylmethyl claim 7 , cyclobutyl claim 7 , cyclopentyl claim 7 , cyclohexyl claim 7 , —(CH)—O—CH claim 7 , —C(CH) ...

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Номер записи: 30
14-01-2021 дата публикации

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

Номер: US20210009528A1
Автор: Berlin Michael, CREW Andrew P., Crews Craig M., Dong Hanqing, Hornberger Keith R., Snyder Lawrence B., Wang Jing, Zimmermann Kurt
Принадлежит:

The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor. 134.-. (canceled) This application is a continuation of U.S. application Ser. No. 16/577,901, filed Sep. 20, 2019, now allowed, which is a divisional application of U.S. application Ser. No. 15/730,728, filed Oct. 11, 2017, now U.S. Pat. No. 10,584,101, which claims priority to, and the benefit of, U.S. Provisional Application No. 62/406,888, filed Oct. 11, 2016, and U.S. Provisional Application No. 62/528,385, filed Jul. 3, 2017, all of which are incorporated by reference in their entirety for all purposes.This invention was made with government support under grant number 1R44CA203199-01 by the National Cancer Institute. The government has certain rights in the invention.U.S. patent application Ser. No. 14/686,640, filed on Apr. 14, 2015, published as U.S. Patent Application Publication No. 2016/0058872; U.S. patent application Ser. No. 14/792,414, filed on Jul. 6, 2015, published as U.S. Patent Application Publication No. 2015/0291562; U.S. patent application Ser. No. 14/371,956, filed on Jul. 11, 2014, published as U.S. Patent Application Publication No. 2014/0356322; U.S. patent application Ser. No. 15/074,820, filed on Mar. 18, 2016, published as U.S. Patent Application Publication No. 2016/0272639, are incorporated herein in their entireties. Furthermore, all references cited herein are incorporated by ...

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Номер записи: 31
10-01-2019 дата публикации

Compounds and uses thereof for the modulation of hemoblogin

Номер: US20190010121A1
Автор: II Stephen L. Gwaltney, Qing Xu, Zhe Li
Принадлежит: Global Blood Therapeutics Inc

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

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Номер записи: 32
09-01-2020 дата публикации

HERBICIDAL MIXTURES

Номер: US20200010443A1
Автор: Dallimore Jonathan Wesley Paul, Mathews Christopher John, MORRIS James Alan
Принадлежит: SYNGENTA PARTICIPATIONS AG

The present invention provides a composition comprising (A) a compound of formula (I): wherein Ris methyl or methoxy, Ris hydrogen, methyl or ethoxy and A is a substituted heteroaryl group, or an N-oxide or salt form thereof, and (B) one or more further herbicides; as well as the use of such compositions in controlling plants or inhibiting plant growth. 2. The composition of claim 1 , Ris H or C-Calkyl.3. The composition according to claim 1 , wherein p is 1 claim 1 , 2 claim 1 , or 3.4. The composition according to wherein n is 1 claim 1 , 2 claim 1 , or 3.5. The composition according to wherein each Ris independently chloro claim 1 , fluoro claim 1 , C-Chaloalkyl claim 1 , or C-Chaloalkoxy.6. The composition according to wherein each Ris independently chloro claim 1 , fluoro claim 1 , C-Chaloalkyl claim 1 , or C-Chaloalkoxy.8. The composition of claim 8 , wherein (B) is compound 2.1.9. The composition of claim 8 , wherein (B) is compound 2.2.10. The composition of claim 8 , wherein (B) is compound 2.3.11. The composition of claim 8 , wherein (B) is compound 2.4.12. The composition of claim 8 , wherein (B) is compound 2.5.13. The composition of claim 8 , wherein (B) is compound 2.6.14. The composition of claim 8 , wherein (B) is compound 2.7.15. The composition of claim 8 , wherein (B) is compound 2.8.16. The composition of claim 8 , wherein (B) is compound 2.9.17. The composition of claim 8 , wherein (B) is compound 2.10.18. The composition of claim 8 , wherein (B) is compound 2.11.19. The composition of claim 8 , wherein (B) is compound 2.12.20. The composition of claim 8 , wherein (B) is compound 2.13.21. The composition of claim 8 , wherein (B) is compound 2.14.22. The composition of claim 8 , wherein (B) is compound 2.15.23. The composition of claim 8 , wherein (B) is compound 2.16.24. The composition of claim 8 , wherein (B) is compound 2.17.25. The composition of claim 8 , wherein (B) is compound 2.18.26. The composition of claim 8 , wherein (B) is compound ...

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Номер записи: 33
18-01-2018 дата публикации

PHOTOSTABLE COMPOUNDS, ABSORBING COMPOUNDS AND USES THEREOF

Номер: US20180016233A1
Автор: Ryan John, YORK Mark
Принадлежит: Commonwealth Scientific and Industrial Research Or ganisation

The present invention describes compounds and uses thereof in applications relating to absorption of electromagnetic energy. Preferred compounds are double bond-containing cyclic compounds capable of absorbing electromagnetic radiation energy and having improved photostability due to the presence and location of one or more fluorine groups in relation to the double bond of the ring. 2. The compound of wherein R′ is selected from Cto Calkenyl claim 1 , Cto Calkynyl claim 1 , Cto Caryl claim 1 , Cto Cheteroaryl claim 1 , Cto Caroyl claim 1 , Cto Calkenone claim 1 , Cto Ccycloalkenyl claim 1 , Cto Ccycloalkenone claim 1 , or Cto Cheterocyclic claim 1 , all of which groups may be substituted or unsubstituted.3. (canceled)5. (canceled)6. The compound of wherein A is a six-membered nitrogen heterocycle comprising at one double bond claim 4 , which nitrogen heterocycle may be further substituted or unsubstituted.7. The compound of wherein A is a six-membered nitrogen heterocycle comprising one double bond and having the carbon atom to which W is attached also attached to a double bonded ring carbon claim 4 , which nitrogen heterocycle may be further substituted or unsubstituted.9. The compound of wherein Rand Rare independently selected from Cto Calkyl claim 8 , Cto Calkenyl or Cto Calkoxy claim 8 , each of which groups may be substituted or unsubstituted.1012-. (canceled)13. The compound of wherein at least one of Rand Rare fluorine or wherein Rand Rcombine to form a 6-membered ring with one or more fluorine substituents on the ring.14. (canceled)15. The compound of wherein Ris selected from halo claim 1 , Cto Calkyl claim 1 , Cto Calkenyl claim 1 , C-Caryl claim 1 , C-Cheteroaryl claim 1 , Cto Calkanone claim 1 , C-Ccycloalkyl claim 1 , C-Ccycloalkanone claim 1 , C-Ccycloalkenyl claim 1 , Cto Calkanoyl claim 1 , Cto Calkanoyloxy claim 1 , Cto Calkoxycarbonyl claim 1 , Cto Ccarbamoyl claim 1 , Cto Ccarboxyl claim 1 , haloalkyl claim 1 , N-alkyl claim 1 , N-aryl claim 1 , ...

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Номер записи: 34
28-01-2016 дата публикации

Novel 3-(4(benzyloxy)phenyl)hex-4-inoic acid derivative, method of preparing same and pharmaceutical composition for preventing and treating metabolic disease including same as effective ingredient

Номер: US20160024063A1
Автор: Chang Mo Son, Daehoon Kim, HAN Kyu Lee, Hyung-Ho Choi, Jae Hyun Kim, Jaekeol Rhee, Jin Woong Kim, Jin Yang, Kyu Hwan Lee, Tae-Young Ha
Принадлежит: Hyundai Pharm Co Ltd

The present invention relates to a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for the prevention and treatment of metabolic disease. The novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention has excellent activities of activating GPR40 protein and promoting insulin secretion accordingly but has no toxicity when co-administered with other drugs. That is, the novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention can be co-administered with other drugs and can promote the activation of GPR40 protein significantly, so that the composition comprising the same as an active ingredient can be efficiently used as a pharmaceutical composition for the prevention and treatment of metabolic disease such as obesity, type I diabetes, type II diabetes, incompatible glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X, etc.

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Номер записи: 35
26-01-2017 дата публикации

Substituted 3-phenylpropylamine derivatives for the treatment of ophthalmic diseases and disorders

Номер: US20170022180A1
Автор: Feng Hong, Mark W. Orme, Ryo Kubota, Vladimir A. Kuksa
Принадлежит: Acucela Inc

The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are substituted 3-phenylpropylamine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compositions are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease.

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Номер записи: 36
22-01-2015 дата публикации

1-cycloalkyl- or 1-heterocyclyl-hydroxyimino-3-phenyl-propanes

Номер: US20150025110A1
Автор: Hans Richter, Henrietta Dehmlow, Patrizio Mattei, Rainer E. Martin, Ulrike Obst Sander
Принадлежит: Hoffmann La Roche Inc

This invention relates to novel 1-cycloalkyl- or 1-heterocyclyl-hydroxyimino-3-phenyl-propanes of the formula wherein R 1 to R 7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

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Номер записи: 37
22-01-2015 дата публикации

SUBSTITUTED PYRIDOXINE-LACTAM CARBOXYLATE-SALTS

Номер: US20150025111A1
Автор: MEGIDDO Dalia, Yamin Rina
Принадлежит:

The present invention provides salt adducts comprising at least one positively charged moiety being a pyridoxine or a derivative thereof and at least one carboxylated 5- to 7-membered lactam ring, optionally additionally substituted, methods of their preparation, and pharmaceutical compositions and medicaments comprising them. Salt adducts of the invention and compositions comprising them may be used to in the treatment of diseases or disorders associated with or inflicted by alcohol consumption, The present application is a continuation of application No. 13/056,943, filed Jan. 31, 2011, which was a National Stage of International Application No. PCT/IL2009/000741, filed Jul. 29, 2009, designating the United States and claiming priority from U.S. Provisional Patent Application No. 61/084,514, filed on Jul. 29, 2008. The foregoing applications are incorporated herein by reference in their entirety.The present invention relates to salt adducts comprising at least one pyridoxine or a derivative thereof and at least one carboxylated 5- to 7-membered lactam ring and uses thereof.Alcohol-induced liver diseases are a common disorder in modern communities and societies. For example, in Europe there are more than 45 million individuals showing signs of alcohol-related damage such as liver disease and myopathies. Chronic alcohol consumption increases hepatic accumulation of triglycerides and leads to hepatic steatosis, which is the earliest and most common response to severe alcohol intoxication.Thus, severe alcohol intoxication is a serious disease that should be treated with medication in order to reduce the damage to the human body of the alcohol intoxicated individual, For example, alcohol intoxication can be treated with metadoxine (pyridoxine L-2-pyrrolidone-5-carboxylate). Metadoxine is a salt of the corresponding anion of L-2-pyrrolidone-5-carboxylic acid (L-2-pyroglutamic acid) (1) and the protonated derivative of pyridoxine (vitamin B6) (2), having the following ...

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Номер записи: 38
24-01-2019 дата публикации

METHOD FOR PRODUCING KAKEROMYCIN AND DERIVATIVES THEREOF

Номер: US20190023667A1
Автор: ISHIKAWA Teruhiko, IWAMI Morita
Принадлежит:

Provided is a production method of kakeromycin and a derivative thereof showing an antifungal activity and cytotoxicity and expected as a new antifungal agent or anticancer agent, by chemical synthesis. A production method of a compound represented by the formula (1): This patent application is a divisional of copending U.S. patent application Ser. No. 15/554,002, filed on Aug. 27, 2017, which the U.S. national phase of International Patent Application No. PCT/JP2016/055891, filed on Feb. 26, 2016, which claims the benefit of Japanese Patent Application No. 2015-039363, filed Feb. 27, 2015, the disclosures of which are incorporated herein by reference in their entireties for all purposes.The present invention relates to a production method of kakeromycin and a derivative thereof.In recent years, along with an increase in elderly people, progress of advanced medicine, immunodeficiency of late stage cancer patients and the like, infections with fungi have been increasing. These infections provide serious effects, often causing death. Since there are not many kinds of existing antifungal agents, and their toxicity is high, the mother nucleus of a new antifungal agent, which is different from that of conventional medicaments, has been desired. In addition, since the use of antifungal agents causes increased emergence of resistant bacteria, the development of a new medicament has been earnestly desired. While candin-based antifungal agents show low toxicity, since the molecular weight thereof is large, reactivity with serum poses problems. Azole-based antifungal agents have a problem in that administration at a high concentration is difficult in view of the toxicity thereof. Therefore, an effective, low-molecular-weight compound showing low reactivity with serum and low toxicity has been strongly desired.Conventionally, in search of a pharmaceutical product seed compound from microbial metabolites, terrestrial separation sources have been mainly harvested and subjected ...

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Номер записи: 39
24-01-2019 дата публикации

METHOD FOR PRODUCING KAKEROMYCIN AND DERIVATIVES THEREOF

Номер: US20190023668A1
Автор: ISHIKAWA Teruhiko, IWAMI Morita
Принадлежит:

Provided is a production method of kakeromycin and a derivative thereof showing an antifungal activity and cytotoxicity and expected as a new antifungal agent or anticancer agent, by chemical synthesis. A production method of a compound represented by the formula (1): This patent application is a divisional of copending U.S. patent application Ser. No. 15/554,002, filed on Aug. 27, 2017, which the U.S. national phase of International Patent Application No. PCT/JP2016/055891, filed on Feb. 26, 2016, which claims the benefit of Japanese Patent Application No. 2015-039363, filed Feb. 27, 2015, the disclosures of which are incorporated herein by reference in their entireties for all purposes.The present invention relates to a production method of kakeromycin and a derivative thereof.In recent years, along with an increase in elderly people, progress of advanced medicine, immunodeficiency of late stage cancer patients and the like, infections with fungi have been increasing. These infections provide serious effects, often causing death. Since there are not many kinds of existing antifungal agents, and their toxicity is high, the mother nucleus of a new antifungal agent, which is different from that of conventional medicaments, has been desired. In addition, since the use of antifungal agents causes increased emergence of resistant bacteria, the development of a new medicament has been earnestly desired. While candin-based antifungal agents show low toxicity, since the molecular weight thereof is large, reactivity with serum poses problems. Azole-based antifungal agents have a problem in that administration at a high concentration is difficult in view of the toxicity thereof. Therefore, an effective, low-molecular-weight compound showing low reactivity with serum and low toxicity has been strongly desired.Conventionally, in search of a pharmaceutical product seed compound from microbial metabolites, terrestrial separation sources have been mainly harvested and subjected ...

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Номер записи: 40
24-01-2019 дата публикации

METHOD FOR PRODUCING KAKEROMYCIN AND DERIVATIVES THEREOF

Номер: US20190023669A1
Автор: ISHIKAWA Teruhiko, IWAMI Morita
Принадлежит:

Provided is a production method of kakeromycin and a derivative thereof showing an antifungal activity and cytotoxicity and expected as a new antifungal agent or anticancer agent, by chemical synthesis. A production method of a compound represented by the formula (1): 1. A compound represented by the formula (6):whereinR is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group,{'sup': '4', 'Ris an optionally substituted hydrocarbon group or an optionally substituted hydrocarbon-oxy group, and'}n is 0 or 1, This patent application is a divisional of copending U.S. patent application Ser. No. 15/554,002, filed on Aug. 27, 2017, which the U.S. national phase of International Patent Application No. PCT/JP2016/055891, filed on Feb. 26, 2016, which claims the benefit of Japanese Patent Application No. 2015-039363, filed Feb. 27, 2015, the disclosures of which are incorporated herein by reference in their entireties for all purposes.The present invention relates to a production method of kakeromycin and a derivative thereof.In recent years, along with an increase in elderly people, progress of advanced medicine, immunodeficiency of late stage cancer patients and the like, infections with fungi have been increasing. These infections provide serious effects, often causing death. Since there are not many kinds of existing antifungal agents, and their toxicity is high, the mother nucleus of a new antifungal agent, which is different from that of conventional medicaments, has been desired. In addition, since the use of antifungal agents causes increased emergence of resistant bacteria, the development of a new medicament has been earnestly desired. While candin-based antifungal agents show low toxicity, since the molecular weight thereof is large, reactivity with serum poses problems. Azole-based antifungal agents have a problem in that administration at a high concentration is difficult in view of the toxicity thereof. Therefore, an ...

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Номер записи: 41
28-01-2021 дата публикации

BUMETANIDE DERIVATIVES FOR THE THERAPY OF HYPERHIDROSIS

Номер: US20210022978A1
Автор: Erker Thomas, Schreppel Philipp
Принадлежит:

The present invention relates to bumetanide derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases/disorders involving Na—K2Cl-cotransporters (NKCCs), and particularly for use in the treatment or prevention of hyperhidrosis. 3. The compound for use according to claim 2 , wherein Ris —COO—(Calkyl) claim 2 , wherein the alkyl moiety of said —COO—(Calkyl) is optionally substituted with one or more groups independently selected from halogen claim 2 , —CF claim 2 , —CN claim 2 , —NO claim 2 , —NH claim 2 , —NH(Calkyl) claim 2 , —N(Calkyl)(Calkyl) claim 2 , —OH claim 2 , —O(Calkyl) claim 2 , —SH and —S(Calkyl) claim 2 , and further wherein one or two —CH— units comprised in the alkyl moiety of said —COO—(Calkyl) are each optionally replaced by a group independently selected from —O— claim 2 , —CO— claim 2 , —COO— claim 2 , —O—CO— claim 2 , —NH— claim 2 , —N(Calkyl)- claim 2 , —NH—CO— claim 2 , —N(Calkyl)-CO— claim 2 , —CO—NH— claim 2 , —CO—N(Calkyl)- claim 2 , —S— claim 2 , —SO— claim 2 , —SO— claim 2 , —SO—NH— claim 2 , —SO—N(Calkyl)- claim 2 , —NH—SO— and —N(Calkyl)-SO—.4. The compound for use according to or claim 2 , wherein Ris —COO—CH.5. The compound for use according to claim 2 , wherein Ris —COOH.6. The compound for use according to claim 2 , wherein Ris selected from —(Calkylene)-NH—(Calkylene)-R claim 2 , —COO—(Calkylene)-R claim 2 , —O—CO—(Calkylene)-R claim 2 , —CO—(Calkylene)-R claim 2 , —CO—NH—(Calkylene)-R claim 2 , —CO—N(Calkyl)-(Calkylene)-R claim 2 , —NH—CO—(Calkylene)-Rand —N(Calkyl)-CO—(Calkylene)-R claim 2 , wherein Ris independently selected from —CF claim 2 , —CN and halogen.7. The compound for use according to or claim 2 , wherein Ris —(Calkylene)-NH—(Calkylene)-CF.8. The compound for use according to any one of to claim 2 , wherein Ris hydrogen.9. The compound for use according to any one of to claim 2 , wherein Ris selected from —SO—NH claim 2 , —SO—NH(Calkyl ...

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Номер записи: 42
28-01-2021 дата публикации

SULFAMOYL-ARYLAMIDES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Номер: US20210024462A1
Автор: Last Stefaan Julien, Raboisson Pierre Jean-Marie Bernard, ROMBOUTS Geert, Vandyck Koen, Verschueren Wim Gaston
Принадлежит:

Inhibitors of HBV replication of Formula (I) 2. The compound according to claim 1 , wherein Rrepresents a 3-7 membered saturated ring claim 1 , containing one or more heteroatoms each independently selected from the group consisting of O claim 1 , S and N claim 1 , such 3-7 membered saturated ring optionally being substituted with one or more substituents each independently selected from the group consisting of hydrogen claim 1 , halo claim 1 , C-Calkyloxy claim 1 , C(═O)—C-Calkyl claim 1 , C-Calkyl claim 1 , OH claim 1 , CN claim 1 , CFH claim 1 , CFH and CF;{'sub': 1', '2', '1', '4', '1', '3', '1', '4', '2', '2', '3, 'Or RRtogether with the Nitrogen to which they are attached form a 5-7 membered saturated ring, optionally containing one or more additional heteroatoms each independently selected from the group consisting of O, S and N, such 5-7 membered saturated ring optionally being substituted with one or more substituents each independently selected from the group consisting of hydrogen, halo, CCalkyloxy, oxo, C(═O)—C-Calkyl, C-Calkyl, OH, CN, CFH, CFH and CF.'}3. The compound according to wherein Rrepresents a 4-7 membered saturated ring containing carbon and one or more oxygen atoms claim 1 , such 4-7 membered saturated ring optionally being substituted with one or more substituents each independently selected from the group consisting of hydrogen claim 1 , halo claim 1 , CCalkyloxy claim 1 , C(═O)—C-Calkyl claim 1 , C-Calkyl claim 1 , OH claim 1 , CN claim 1 , CFH claim 1 , CFH and CF.4. The compound according to claim 1 , wherein B represents phenyl or thiophene claim 1 , optionally being substituted with one or more substituents each independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , C-Calkyl claim 1 , CN claim 1 , CFH claim 1 , CFH and CF.5. The compound according to claim 1 , wherein Rrepresents C-Calkyl-Ror a 4-7 membered saturated ring consisting of carbon atoms and one or more heteroatoms each independently ...

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Номер записи: 43
29-01-2015 дата публикации

CYCLIC AMIDES AS METAP-2 INHIBITORS

Номер: US20150031670A1
Автор: FRIESE-HAMIM Manja, Heinrich Timo, Krier Mireille, SEENISAMY Jeyaprakashnarayanan, Zenke Frank
Принадлежит: Merck Patent GmBH

Compounds of the formula (I), in which R, R, R, R, R, R, X and Y have the meanings indicated in Claim , are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumours. 2. Compounds according to in which{'sub': 2', '2', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', '2', '2', '2', '2', '2', '2, 'sup': 1', '3', '3, 'Het denotes pyrazinyl, pyrazolyl, benzimidazolyl, pyridyl, indolyl, dihydroindolyl, benzofuranyl, tetrahydropyranyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indazolyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, benzothiazolyl, piperidin-1-yl, pyrrolidin-1-yl, 3,4-dihydro-2H-pyrido[3,2-b]-1,4-oxazinyl, 3,4-dihydro-2H-benzo-1,4-oxazinyl, benzofuranyl, azetidinyl, 3-azabicylo[3.2.0]hexyl, pyrrolo[2,3-b]pyridinyl, tetrahydrofuranyl, tetrahydro-1,8-naphthyridinyl, 2,3-dihydrobenzoisothiazolyl, 1,2,3,4-tetrahydrobenzothiazinyl or hexahydrobenzo-1,3-dioxolyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, CN, NH, NHA, NA, NO, CN, COOH, COOA, (CH)CONH, (CH)CONHA, (CH)CONA, NHCOA, COA, CHO, Het, SOA, SONH, SONHA, SONA, CONHNH, CONHAr, ═O and/or Ar,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to in which{'sup': '1', 'Hetdenotes pyridazinyl, pyrazolyl, pyridyl, piperazinyl, morpholinyl, pyrimidinyl, furyl, thienyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, thiadiazole, piperidin-1-yl, pyrrolidin-1-yl, tetrahydropyranyl, 1,2-oxazinan-2-yl, 1,2,5-oxadiazinan-2-yl, 1,3-oxazinan-3-yl or hexahydropyrimidinyl, each of which is unsubstituted or mono-, di- or trisubstituted by A and/or OA,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.4. Compounds according to in which{'sup': 2', '4', '4', '2', '2', '4', '2, 'sub': 2', '2', 'n', '2', 'n, 'R ...

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Номер записи: 44
04-02-2016 дата публикации

NEW ARYLAMINOALCOHOL DERIVATIVES WITH ANTIPLASMODIAL ACTIVITY

Номер: US20160031815A1
Автор: ALDANA MORAZA Ignacio, BLAIR TRUJILLO Silvia Victoria, DEHARO Eric, GARAVITO Giovanny, MENDOZA LIZALDEZ Adela, PEREZ-SILANES Silvia
Принадлежит: INSTITUT DE RECHERCHE POUR LE DEVELOPPEMENT

The present invention relates to new arylaminoalcohol derivatives of formula (I), and to a method for the preparation of such compounds: I The invention also relates to the use of these compounds as medicaments, and in particular for the prevention and/or the treatment of parasitic diseases caused by apicomplexan parasites such as malaria and toxoplasmosis. Finally, the invention relates to pharmaceutical compositions containing such compounds of formula (I) as active principles. 2. Compound according to claim 1 , wherein the aromatic group Ar is substituted by an halogen atom claim 1 , and preferably by a fluorine atom.3. Compound according to claim 2 , wherein the aromatic group Ar is selected from the 4-fluoro-1-phenyl and 4-fluoro-1-naphtyl groups claim 2 , and preferably Ar is the 4-fluoro-1-phenyl group.4. Compound according to claim 1 , wherein the amino entity Am is a tetrahydropyridine entity.5. Compound according to claim 1 , wherein R is —NOor —F.6. Compound according to claim 1 , wherein R′ is —H or —CF.7. Compound according to claim 5 , wherein R═—NOand R′═—CF.9. Compound of formula (I) according to claim 1 , or one of its tautomeric claim 1 , racemic claim 1 , enantiomeric or polymorphic forms or pharmaceutically acceptable salts claim 1 , for its use as a medicament.10. Compound of formula (I) for its use according to claim 9 , for the prevention and/or the treatment of parasitic diseases involving apicomplexan parasites.11Plasmodium, Babesia, Toxoplasma, Neospora, Cryptosporidium, Theileria, SarcosystisEimeria.. Compound of formula (I) for its use according to claim 10 , wherein said apicomplexan parasites are selected from and12. Compound of formula (I) for its use according to for the prevention and/or the treatment of malaria.13. Compound of formula (I) for its use according to to for the prevention and/or the treatment of toxoplasmosis.14. Compound of formula (I) for its use according to for the prevention and/or the treatment of AIDS virus.15. A ...

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Номер записи: 45
31-01-2019 дата публикации

Sulfamide derivatives and preparation method and use thereof

Номер: US20190031612A1
Автор: Dengfeng Dou, Jin Li, Jingming Li, Jinqiao Wan, Linli Li, Wei Zhang, Xueming Li, Yan Lan
Принадлежит: Hitgen Inc

The present invention discloses a compound shown in formula I or a stereoisomer, pharmaceutically acceptable salt, crystal form, solvate or isotopologue thereof. The compound of the present invention shows excellent inhibition activity against histone deacetylases, has remarkable inhibition effects on cancer cells, and provides a new choice of drugs used for the clinic treatment and diseases related to the abnormal activity of histone deacetylases.

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Номер записи: 46
07-02-2019 дата публикации

Necrosis Inhibitors

Номер: US20190038578A1
Автор: REN Yan, Ruan Hanying, Su Yaning, Wang Xiaodong, ZHANG Zhiyuan
Принадлежит: National Institute of Biological Sciences, Beijing

The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition. 2. The compound of claim 1 , wherein:{'sub': '1', 'Ris substituted or unsubstituted: phenyl, cyclohexyl, furan, thiophene or azole;'}{'sub': '2', 'Ris substituted or unsubstituted: aziridine, azetidine, pyrrolidine, piperidine, oxazolidine, oxazinane; diazolidine, diazinane, pyrrole, dihydropyrrole, dihydropyridine, or tetrahydropyridine; and'}{'sub': '3', 'Ris 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, or 1,1-dimethylprop-2-ynyl, each optionally fluorinated with 1-4 F atoms; or'}a corresponding sulfonamide of the amide compound, ora pharmaceutically acceptable salt, hydrate or stereoisomer of the compound or corresponding sulfonamide.3. The compound of claim 1 , wherein:{'sub': '1', 'Ris substituted or unsubstituted: phenyl, cyclohexyl, furan, thiophene or azole;'}{'sub': '2', 'Ris substituted or unsubstituted: azetidine, pyrrolidine, piperidine, oxazolidine, diazolidine, or diazinane; and'}{'sub': '3', 'Ris 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, or 1,1-dimethylprop-2-ynyl, each optionally fluorinated with 1-4 F atoms; or'}a corresponding sulfonamide of the amide compound, ora pharmaceutically acceptable salt, hydrate or stereoisomer of the compound or corresponding sulfonamide.4. The compound of claim 1 , wherein:{'sub': '1', 'Ris substituted or unsubstituted: phenyl, cyclohexyl, furan, thiophene or azole;'}{'sub': '2', 'Ris substituted or unsubstituted: azetidine or pyrrolidine; and'}{'sub': '3', 'Ris 1,1-dimethylpropyl, 1,1-dimethylprop-2-enyl, or 1,1-dimethylprop- ...

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Номер записи: 47
24-02-2022 дата публикации

METHOD FOR PRODUCING FLUOROVINYL AMIDE COMPOUND

Номер: US20220055990A1
Автор: HOSHIYA Naoyuki, KISHIKAWA Yosuke, MATSUI Motoshi
Принадлежит: DAIKIN INDUSTRIES, LTD.

An object of this disclosure provides a novel method for producing a fluorovinyl amide compound and the like. The object is achieved by a method for producing a compound represented by formula (1): 2. The production method according to claim 1 , wherein Rf is —F or perfluoroalkyl.3. The production method according to claim 1 , wherein Ris —H claim 1 , an alkyl group optionally substituted with one or more substituents claim 1 , or an aromatic ring group optionally substituted with one or more substituents.4. The production method according to claim 1 , wherein Ris —H claim 1 , an alkyl group optionally substituted with one or more substituents claim 1 , or an aromatic ring group optionally substituted with one or more substituents.5. The production method according to claim 1 , wherein either Ror Ris —H claim 1 , and the other is —H or an aromatic ring group optionally substituted with one or more substituents.6. The production method according to claim 1 , wherein Ris a halo group or a sulfonic acid ester group.7. The production method according to claim 1 ,wherein{'sup': ['b1', 'b', 'h'], 'claim-text': ['wherein', {'sup': 'h', '#text': 'Ris'}, 'an aliphatic hydrocarbyl group optionally substituted with one or more substituents,', 'wherein one or more heteroatoms selected from the group consisting of O, S, and Si may be inserted into the aliphatic hydrocarbyl group, or', 'an aromatic ring group optionally substituted with one or more substituents, and', {'sup': ['b', 'r', 'r'], '#text': 'Lis a single bond, —NR—, —O—, or —S—, and Ris —H or an alkyl group.'}], '#text': 'Ris -L-R,'}8. The production method according to claim 1 ,wherein{'sup': ['b2', 'b', 'h'], 'claim-text': ['wherein', {'sup': 'h', '#text': 'Ris'}, 'an aliphatic hydrocarbyl group optionally substituted with one or more substituents,', 'wherein one or more heteroatoms selected from the group consisting of O, S, and Si may be inserted into the aliphatic hydrocarbyl group, or', 'an aromatic ring group ...

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Номер записи: 48
18-02-2021 дата публикации

HETEROCYCLIC P2Y14 RECEPTOR ANTAGONISTS

Номер: US20210047293A1
Автор: Ciancetta Antonella, Jacobson Kenneth A., JUNG Young-Hwan, Wen Zhiwei, Yu Jinha
Принадлежит: The United States of America,as represented by the Secretary,Department of Health and Human Services

Disclosed are compounds of formulas (I)-(IX) for treating or preventing a disease or disorder responsive to antagonism of a P2YR receptor agonist in a mammal in need thereof, wherein R-R, X, Y, Z, X′, Y′, Z′, and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney. 2. The compound or salt of claim 1 , wherein X claim 1 , Y claim 1 , and Z are all CH.3. (canceled)6. A pharmaceutical composition comprising a compound or salt of and a pharmaceutically acceptable carrier.7. A method for antagonizing a P2YR receptor in a mammal in need thereof claim 1 , comprising administering to the mammal an effective amount of a compound or salt of .8. A method for treating or preventing an inflammatory condition in a mammal in need thereof claim 1 , comprising administering to the mammal an effective amount of a compound or salt of .9. The of claim 8 , wherein the inflammatory condition is selected from the group consisting of asthma claim 8 , cystic fibrosis claim 8 , and sterile inflammation of the kidney.11. The compound or salt of claim 10 , wherein Ris COOH.1318.-. (canceled)21. (canceled)23. A pharmaceutical composition comprising a compound or salt of and a pharmaceutically acceptable carrier.24. A method for antagonizing a P2YR receptor in a mammal in need thereof claim 10 , comprising administering to the mammal an effective amount of a compound or salt of .25. A method for treating or preventing an inflammatory condition in a mammal in need thereof claim 10 , comprising administering to the mammal an effective amount of a compound or salt of .26. The method of claim 25 , wherein the inflammatory condition is selected from the group consisting of asthma claim 25 , cystic fibrosis claim 25 , and sterile inflammation of the kidney. This patent application claims the benefit of U.S. Provisional Patent Application No. 62/628,699 filed Feb. 9, 2018, the disclosure of which is incorporated ...

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Номер записи: 49
18-02-2016 дата публикации

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Номер: US20160046613A1
Автор: GWALTNEY, HARRIS Jason R., II Stephen L., LI Zhe, Metcalf Brian W., Xu Qing, YEE Calvin W.
Принадлежит: Global Blood Therapeutics, Inc.

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 6. The compound of claim 4 , wherein ring A is{'sub': 1', '6, 'phenyl substituted with 1-3 halo or C-Calkoxy, or'}{'sub': 3', '8, 'C-Cheterocyclyl containing 1-3 heteroatoms wherein the heterocycle is optionally substituted with 1-3 halo.'}10. The compound of claim 4 , wherein CVVis C═V claim 4 , wherein V is O claim 4 , and wherein the remaining variables are defined as in .1681015. A composition comprising a compound of any one of - and - claims 3 , and at least one pharmaceutically acceptable excipient.1781015. A method for increasing oxygen affinity of hemoglobin S in a subject claims 3 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of - and - or the composition of .1881015. A method for treating oxygen deficiency associated with sickle cell anemia claims 3 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of - and - or the composition of . This invention provides compounds and pharmaceutical compositions suitable as allosteric modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.Sickle cell disease is a disorder of the red blood cells, found particularly among those of African and Mediterranean descent. The basis for sickle cell disease is found in sickle hemoglobin (HbS), which contains a point mutation relative to the prevalent peptide sequence of hemoglobin (Hb).Hemoglobin (Hb) transports oxygen molecules from the lungs to various tissues and organs ...

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Номер записи: 50
16-02-2017 дата публикации

2-Amino-3-Fluoro-3-(Fluoromethyl)-6-Methyl-6-Phenyl-3,4,5,6-Tetrahydropyridines as BACE1 Inhibitors

Номер: US20170044151A1
Автор: Juhl Karsten, Marigo Mauro, Tagmose Lena
Принадлежит: H. Lundbeck A/S

The present invention provides compounds of Formula I 3. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris halogen.4. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris fluoro.5. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris hydrogen.6. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris fluoro.7. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is pyridyl.8. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is pyrimidyl.9. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is pyrazinyl.10. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is oxazolyl.11. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is imidazolyl.12. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is thiazolyl.13. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is pyrazolyl.14. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is isoxazolyl.15. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is phenyl.16. The compound according to claim 1 , wherein Ar is substituted by one or more substituents selected from the group consisting of: F claim 1 , Cl claim 1 , Br claim 1 , CN claim 1 , C-Calkyl claim 1 , C-Chaloalkyl and C-Calkoxy.17. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein said compound is selected from the group consisting of:(1) N-(3-((2S,5S)-6-amino-5-fluoro-5-(fluoromethyl)-2-methyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-methoxypicolinamide;(2) N ...

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Номер записи: 51
16-02-2017 дата публикации

HISTONE DEACETYLASE INHIBITORS

Номер: US20170044186A1
Автор: Jacques Vincent, Peet Norton P., Rusche James R., Singh Jasbir
Принадлежит:

This invention relates to generally inhibiting histone deacetylase (“HDAC”) enzymes (e.g., HDAC1, HDAC2, and HDAC3). 2. The compound or salt of claim 1 , wherein n is 1.3. The compound or salt of claim 2 , wherein X is —Y—[C(R)]-A-[C(R)]—B—.4. The compound or salt of claim 3 , wherein A is a bond and/or B is a bond.5. The compound or salt of or claim 3 , wherein each occurrence of Rand R(when present) is independently selected from H claim 3 , F claim 3 , OH claim 3 , C1-C6 alkyl claim 3 , C3-C6 cycloalkyl claim 3 , NH claim 3 , OCO—(C1-C6 alkyl) claim 3 , OCO—(C3-C6 cycloalkyl) claim 3 , C1-C6 alkoxy C1-C6 fluoroalkoxy claim 3 , and cyano.6. The compound or salt according to any one of - claim 3 , wherein each occurrence of Rand R(when present) is independently selected from H claim 3 , F claim 3 , C1-C6 alkyl claim 3 , and C3-C6 cycloalkyl.7. The compound or salt according to any one of - claim 3 , wherein each occurrence of Rand R(when present) is H.8. The compound or salt of claim 3 , wherein Y is CR═CR.9. The compound or salt of claim 8 , wherein the double bond between CRand CRhas the trans configuration.10. The compound or salt of or claim 8 , wherein each of Rand Ris H.11. The compound or salt according to any one of - claim 8 , wherein A is a bond and/or B is a bond.12. The compound or salt according to any one of - claim 8 , wherein each occurrence of Rand R(when present) is independently selected from H claim 8 , F claim 8 , OH claim 8 , C1-C6 alkyl claim 8 , C3-C6 cycloalkyl claim 8 , NH claim 8 , OCO—(C1-C6 alkyl) claim 8 , OCO—(C3-C6 cycloalkyl) claim 8 , C1-C6 alkoxy C1-C6 fluoroalkoxy claim 8 , and cyano.13. The compound or salt according to any one of - claim 8 , wherein each occurrence of Rand R(when present) is independently selected from H claim 8 , F claim 8 , C1-C6 alkyl claim 8 , and C3-C6 cycloalkyl.14. The compound or salt according to any one of - claim 8 , wherein each occurrence of Rand R(when present) is H.15. The compound or salt ...

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Номер записи: 52
15-02-2018 дата публикации

Biguanide compound and use thereof

Номер: US20180044283A1
Автор: Hong Bum Lee, Hong Woo Kim, Hye Jin Heo, Jae Kap Jeong, Ji Ae KOOK, Ji Sun Lee, Sung Wuk Kim
Принадлежит: IMMUNOMET THERAPEUTICS INC

The present invention relates to a guanidine compound and a use thereof, and more specifically, to a guanidine derivative showing excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence; a preparation method thereof; and a pharmaceutical composition containing the same as an active ingredient. Compared to existing drugs, the guanidine derivative according to the present invention shows excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence even with small doses, and may thus be effectively used in preventing or treating various cancers such as uterine cancer, breast cancer, stomach cancer, brain cancer, rectal cancer, colorectal cancer, lung cancer, skin cancer, blood cancer, liver cancer, etc., inhibiting cancer cell proliferation and cancer metastasis.

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Номер записи: 53
19-02-2015 дата публикации

PROCESS FOR PREPARING LACTAMS

Номер: US20150051401A1
Автор: Jacquot Roland, Marion Philippe
Принадлежит:

The present invention relates to a method for preparing lactams using heterogeneous catalysis by hydrogenating at least one compound of the following formula (I), where A is a radical of the following formula (I′) or (II′): —CH(R)—CH(R)— (I′); or —CH(R)—CH(R)—CH(R)— (II′); where R, Rand Rare, independently from each other, H, OH, an alkyl radical, or a cycloalkyl radical; and R is H or a straight or branched alkyl radical having 1 to 20, preferably 1 to 10, and more preferably 1 to 4 carbon atoms. Said method is carried out at a pressure of less than 60 bars, preferably 10 to 50 bars, in the presence of a solid hydrogenation catalyst including at least two metals selected from the group of noble metals and transition metals, and an inert substance used as a support, wherein said compound of formula (I) can be used alone or as part of a mixture. 2. The process of claim 1 , wherein the hydrogenation is carried out in the absence of solvent.3. The process of claim 1 , wherein the hydrogenation is carried out in the liquid phase.4. The process of claim 1 , wherein R claim 1 , Rand Rrepresent H or a (C-C)alkyl radical.5. The process of claim 1 , wherein A is a radical of formula —CH—CH—CH(R′)— claim 1 , and R′ represents a (C-C)alkyl radical claim 1 , and preferably methyl or ethyl.6. The process of claim 1 , wherein R is H.7. The process of claim 1 , wherein the hydrogenation is carried out at a temperature greater than or equal to 105° C.9. The process of claim 1 , wherein the pressure is between 10 bar and 50 bar.10. The process of claim 1 , wherein R represents a linear or branched alkyl radical comprising from 1 to 10 carbon atoms.11. The process of claim 1 , wherein the hydrogenation catalyst is a mixture of at least two metals selected from the group consisting of ruthenium claim 1 , platinum claim 1 , palladium claim 1 , iridium and rhodium claim 1 , said mixture being supported by an inert substance.12. The process of claim 1 , wherein the hydrogenation catalyst ...

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Номер записи: 54
03-03-2022 дата публикации

AMINOCARBAMOYL COMPOUNDS FOR THE TREATMENT OF VIRAL INFECTIONS

Номер: US20220064128A1
Автор: CHEN Jianguo, Liang Chungen, Miao Kun, Wu Yao, Yun Hongying, ZHANG WEIXING
Принадлежит: Hoffmann-La Roche Inc.

The present invention relates to compounds of formula (I),

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Номер записи: 55
14-02-2019 дата публикации

KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF

Номер: US20190047977A1
Автор: Dominguez Celia, Mitchell William, Prime Michael, Toledo-Sherman Leticia, Went Naomi
Принадлежит:

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity. 133.-. (canceled)35. The method of claim 34 , wherein said condition or disorder involves a neurodegenerative pathology.36. The method of claim 34 , wherein said condition or disorder is Huntington's Disease.38. The method of claim 37 , wherein said condition or disorder involves a neurodegenerative pathology.39. The method of claim 37 , wherein said condition or disorder is Huntington's Disease. This application is a continuation of U.S. patent application Ser. No. 14/392,307, filed Dec. 23, 2015, which claims the benefit of priority under 35 U.S.C. § 371 of PCT International Application No. PCT/US2014/056887, filed Sep. 23, 2014, which in turn claims the benefit of priority to U.S. Provisional Application No. 61/882,813, filed Sep. 26, 2013, both of which are incorporated herein by reference ...

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Номер записи: 56
25-02-2016 дата публикации

Novel heterocyclic derivative and pharmaceutical composition comprising the same (as amended)

Номер: US20160052892A1
Автор: Hiroyuki Kai, Kentaro Asahi, Sae Jikihara, Takeshi Endoh, Tohru Horiguchi
Принадлежит: Shionogi and Co Ltd

The present invention provides novel compounds having a P2X 3 and/or P2X 2/3 receptor antagonistic effect. A pharmaceutical composition having a P2X 3 and/or P2X 2/3 receptor antagonistic effect comprising a compound of the formula (I): wherein ring A is substituted or unsubstituted 5 to 7-membered cycloalkane, substituted or unsubstituted 5 to 7-membered cycloalkene or the like; C is a carbon atom; —X— is —N(R 16 )— or the like; R 16 is hydrogen, substituted or unsubstituted alkyl or the like; R 7 is substituted or unsubstituted 5- or 6-membered heteroaryl, substituted or unsubstituted 6 to 10 membered aryl; Q 1 and Q 2 are each independently a carbon atom or a nitrogen atom; -L- is —O—, —S— or the like; R 6 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl or the like; R 2 is hydrogen, hydroxy or the like, or its pharmaceutically acceptable salt or a solvate thereof.

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Номер записи: 57
13-02-2020 дата публикации

METHODS FOR ENANTIOSELECTIVE ALLYLIC ALKYLATION OF ESTERS, LACTONES, AND LACTAMS WITH UNACTIVATED ALLYLIC ALCOHOLS

Номер: US20200048201A1
Автор: Bachman Shoshana, Jette Carina I., Lackner Sebastian, Ngamnithiporn Aurapat, Stoltz Brian M., Virgil Scott C.
Принадлежит:

The present disclosure provides methods for enantioselective synthesis of cyclic and acyclic α-quaternary carboxylic acid derivatives via nickel-catalyzed allylic alkylation. 113-. (canceled)15. The method of claim 14 , wherein:{'sub': '2', 'the Ni(0) source is Ni(COD);'}L is (S)—C3-TunePhos; andthe organic solvent is diethyl ether.16. The method of claim 14 , wherein:{'sub': '6', 'Ris methyl; and'}{'sub': '7', 'Ris methyl.'}17. (canceled)18. The method of claim 15 , wherein:{'sub': '6', 'Ris methyl; and'}{'sub': '7', 'Ris methyl.'}19. A method comprising{'claim-ref': {'@idref': 'CLM-00014', 'claim 14'}, 'preparing a compound of Formula (XI) according to ; and'}synthesizing a pharmaceutical agent from the compound of Formula (XI).21. The method of claim 20 , wherein:{'sub': '2', 'the Ni(0) source is Ni(COD);'}L is (S)—C3-TunePhos; andthe organic solvent is diethyl ether.22. The method of claim 20 , wherein:{'sub': '6', 'Ris methyl; and'}{'sub': '7', 'Ris methyl.'}23. The method of claim 21 , wherein:{'sub': '6', 'Ris methyl; and'}{'sub': '7', 'Ris methyl.'} This Application claims the benefit of U.S. Provisional Application 62/580,091, filed Nov. 1, 2017, the contents of which are hereby incorporated herein by reference.This invention was made with government support under Grant Nos. GM080269 awarded by the National Institutes of Health. The Government has certain rights in the invention.Synthetic methods for the generation of enantioenriched quaternary stereocenters are highly desirable given their prevalence as motifs in a wide variety of biologically active molecules of both natural and unnatural origin, and the pharmaceutical industries increasing recognition for the motif's applicability in drug design. Despite their importance, the number of highly enantioselective transformations that construct quaternary stereocenters under mild reaction conditions is limited, with respect to both cyclic and acyclic systems.Since 1965, transition metal-catalyzed allylic ...

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Номер записи: 58
22-02-2018 дата публикации

Water Soluble Homogeneous Catalysts That Are Recoverable By Phase Selectivity And Host-Guest Interactions

Номер: US20180050332A1
Автор: Chung Hoyong
Принадлежит: FLORIDA STATE UNIVERSITY RESEARCH FOUNDATION, INC.

This describes homogeneous catalysts that are recoverable from solution by being phase selective and through host-guest interactions. An example of a method includes separating a water soluble N-heterocyclic carbene homogeneous catalyst from a solution by: (a) forming a host-guest compound between the catalyst and an inclusion compound in the solution; and (b) isolating the host-guest compound from the solution. 1. A method comprising: (a) forming a host-guest compound between the catalyst and an inclusion compound in the solution; and', '(b) isolating the host-guest compound from the solution., 'separating a water soluble N-heterocyclic carbene homogeneous catalyst from a solution by2. The method of claim 1 , wherein the catalyst includes a polyethylene glycol functional group bonded to an N-heterocyclic carbene moiety.3. The method of claim 1 , wherein the catalyst includes a transition metal bonded to an N-heterocyclic carbene moiety bonded to a polyethylene glycol functional group.4. The method of claim 1 , wherein the catalyst includes a transition metal bonded to an N-heterocyclic carbene moiety bonded to a polyethylene glycol functional group bonded to a terminal adamantyl group.5. The method of claim 1 , wherein the inclusion compound is a cyclodextrin.6. The method of claim 1 , wherein the inclusion compound is a cyclodextrin attached to a surface of a solid substrate.7. The method of claim 1 , wherein the solution is an olefin metathesis reaction solution.9. A method comprising:catalyzing a chemical reaction in an organic solvent using a water soluble N-heterocyclic carbene homogeneous catalyst to form a reaction mixture;forming an aqueous phase in the reaction mixture;adding a solvent in which the catalyst is insoluble to the reaction mixture causing the catalyst to migrate to the aqueous phase to form a catalyst-laden aqueous phase; andextracting the catalyst-laden aqueous phase from the reaction mixture.10. The method of claim 9 , wherein the catalyst ...

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Номер записи: 59
25-02-2021 дата публикации

BIOCATALYSTS AND METHODS FOR THE SYNTHESIS OF SUBSTITUTED LACTAMS

Номер: US20210054352A1
Автор: Cabirol Fabien Louis, Chen Haibin, Gohel Anupam, Hsieh Helen, Janey Jacob, Kosjek Birgit, Pham Son Q., Salim Paulina Elena, Smith Derek J., Tang Weng Lin
Принадлежит:

The present disclosure relates to transaminase polypeptides capable of aminating a dicarbonyl substrate, and polynucleotides, vectors, host cells, and methods of making and using the transaminase polypeptides. 1. An engineered polynucleotide encoding an engineered transaminase polypeptide comprising an amino acid sequence having at least 80% sequence identity to reference sequence SEQ ID NO:4 and at least an amino acid residue difference as compared to SEQ ID NO:4 at residue position X323.2. The engineered polynucleotide encoding an engineered polypeptide of claim 1 , in which X323 is selected from C claim 1 , E claim 1 , N claim 1 , and R.3. The engineered polynucleotide encoding an engineered polypeptide of claim 2 , wherein the amino acid sequence further comprises one or more residue differences as compared to SEQ ID NO:4 selected from: X42G; X54P; X54R; X69A; X69G; X69T; X122M; X124F; X124L; X124N; X124R; X126A; X126T; X150S; X152C; X152G; X152I; X152L; X152S; X156A; X156S; X156T; X157L; X165N claim 2 , X192A claim 2 , X193G claim 2 , X192H claim 2 , X192K claim 2 , X192N claim 2 , X193Q claim 2 , X192R claim 2 , and X192S.4. The engineered polynucleotide encoding an engineered polypeptide of claim 2 , wherein the amino acid sequence further comprises a combination of residue differences selected from:(a) X124W and X327L;(b) X209M and X300G;(c) X122F, X223V and X284A;(d) XI92A, X215H and X311T;(e) X62N, X124F, X126A and X136L;(f) X124W, X126A, X136L, X192A and X284A; and(g) X124W, X126A, X136L, X152R/X152L/X152I, and X192A.5. The engineered polynucleotide encoding an engineered polypeptide of claim 1 , in which the amino acid sequence further comprises at least one or more residue differences as compared to SEQ ID NO:4 selected from: X54A; X54L; X56D; X56E; X61G; X61W; X62A; X62L; X62N; X62S; X64C; X68I; X122F claim 1 , X122W; X122Y; X124K; X124M; X124S; X124W; X126C; X126I; X139E; X140K; X143V; X150L; X155I; X155L; X159G; X160L; X176C; X199L; X199V; X209F; ...

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Номер записи: 60
21-02-2019 дата публикации

Methods of preparing hydroxylamine derivatives useful in the preparation of anti-infective agents

Номер: US20190055216A1
Автор: Aaron M. Dumas, DongFang Meng, Feng Yu, Jeremy P. Scott, John Y. L. Chung, Michael Shevlin, Zhijian Liu
Принадлежит: Merck Sharp and Dohme LLC, Merck Sharp and Dohme Ltd

The present invention relates to processes for the preparation of N-protected 4-((2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxamido)piperidine-1-carboxylates. Such compounds have application in the preparation of beta-lactamase inhibitors such as 7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamides and esters, in particular, the beta lactamase inhibitor, (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. The present invention also encompasses intermediates useful in the disclosed processes and methods for their preparation.

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Номер записи: 61
20-02-2020 дата публикации

C7-fluoro substituted tetracycline compounds

Номер: US20200055813A1
Автор: Diana K. Hunt, Jingye Zhou, Louis Plamondon, Robert Zahler, Roger B. Clark, Xiao-Yi Xiao
Принадлежит: Tetraphase Pharmaceuticals Inc

The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

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Номер записи: 62
05-03-2015 дата публикации

Novel compound and photosensitive resin composition

Номер: US20150064623A1
Автор: Daisuke Sawamoto, Hirokatsu Shinano, Koichi Kimijima, Nobuhide Tominaga, Takeo Oishi
Принадлежит: Adeka Corp

A novel compound having satisfactory sensitivity (base generating performance), a photosensitive resin composition containing the compound as a photo-initiator, and a cured product of the composition are provided. Specifically, a compound represented by general formula (1) (compound (1)), a photosensitive resin composition containing (A) a photo-initiator including at least one compound (1) and (B) a photosensitive resin are provided. Preferred are the compound (1) in which R 1 is an unsubstituted or substituted C6-C20 aromatic hydrocarbon group, the compound (1) in which at least one of R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 is nitro, and the compound (1) in which n is 0. The symbols in general formula (1) are as defined in the description.

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Номер записи: 63
22-05-2014 дата публикации

SKIN WOUND HEALING AND SCAR REDUCTION WITH PROSTAGLANDIN EP4 AGONIST COMBINATIONS

Номер: US20140142042A1
Автор: Burk Robert M., IM WHA-BIN, Jiang Guang L., Wheeler Larry A.
Принадлежит: ALLERGAN, INC.

A combination of a prostaglandin EP4 agonist and an effective amount of: a prostaglandin EP2 agonist, a skin growth factor, a small peptide, a small inhibitory RNA targeting excess chronic inflammation or fibrosis, a cytokine with beneficial anti-inflammatory activity, an adenosine A2a receptor agonist, an anti-oxidant, or a combination thereof, may be used to treat skin wounds or scars. 1. A method of treating a skin wound or a scar comprising administering an effective amount of a prostaglandin EP4 agonist and an effective amount of an additional compound selected from the group consisting of a prostaglandin EP2 agonist , a skin growth factor , a small peptide , a small inhibitory RNA targeting excess chronic inflammation or fibrosis , a cytokine with beneficial anti-inflammatory activity , an adenosine A2a receptor agonist , an anti-oxidant , or a combination thereof , to a mammal in need thereof.9. The method of claim 1 , comprising administering an effective amount of a prostaglandin EP4 agonist and an effective amount of a prostaglandin EP2 agonist.10. The method of claim 9 , wherein the prostaglandin EP4 agonist and the prostaglandin EP2 agonist are administered topically.11. The method of claim 9 , wherein the prostaglandin EP4 agonist and the prostaglandin EP2 agonist are administered orally.12. The method of claim 9 , wherein the prostaglandin EP4 agonist and the prostaglandin EP2 agonist are administered in a single composition.13. The method of claim 9 , wherein the prostaglandin EP4 agonist and the prostaglandin EP2 agonist are administered at least daily for about 1 day to about 30 days.16. The method of wherein the EP4 agonist and the additional compound are applied directly to the skin wound or the scar.17. The method of wherein the EP4 agonist and the additional compound are applied directly to the skin surrounding the skin wound or the scar.18. The method of wherein the EP4 agonist and the additional compound are applied to a surgical site from ...

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Номер записи: 64
28-02-2019 дата публикации

Piperidinone Derivatives as MDM2 Inhibitors for the Treatment of Cancer

Номер: US20190062276A1
Автор: BARTBERGER Michael D., BECK Hilary Plake, Chen Xiaoqi, Connors Richard Victor, Deignan Jeffrey, Duquette Jason A., EKSTEROWICZ John, FISHER BENJAMIN, FOX Brian M., FU Jiasheng, FU Zice, GONZALEZ BUENROSTRO Ana, Gonzalez Lopez De Turiso Felix, Gribble, Gustin Darin J., Heath Julie A., HUANG Xin, JIAO XianYun, Johnson Michael G., JR. Michael W., KAYSER Frank, Kopecky David John, LAI SuJen, LI Yihong, LI Zhihong, Liu Jiwen, Low Jonathan D., Lucas Brian S., Ma Zhihua, McGee Lawrence R., McIntosh Joel, MCMINN Dustin L., MEDINA Julio C., Mihalic Jeffrey Thomas, OLSON Steven H., REW Yosup, ROVETO Philip M., SUN Daqing, Wang Xiaodong, WANG Yingcai, YAN Xuelei, Yu Ming, ZHU Jiang
Принадлежит:

The present invention provides MDM2 inhibitor compounds of Formula I, 130-. (canceled)31. A pharmaceutical composition comprising a compound of 2-(3R ,5R ,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid , or a pharmaceutically acceptable salt thereof.32. The pharmaceutical composition of claim 31 , further comprising microcrystalline cellulose.33. The pharmaceutical composition of claim 31 , further comprising lactose.34. The pharmaceutical composition of claim 31 , further comprising carboxymethylcellulose.35. The pharmaceutical composition of claim 31 , further comprising magnesium stearate.36. The pharmaceutical composition of claim 31 , in a dosage form formulated for topical administration.37. The pharmaceutical composition of claim 36 , wherein the dosage form is an ointment.38. The pharmaceutical composition of claim 36 , wherein the dosage form is spray.39. The pharmaceutical composition of claim 36 , wherein the dosage form is inhalants.40. The pharmaceutical composition of is in a dosage form for oral administration.41. The pharmaceutical composition of claim 40 , wherein the dosage form is tablets.42. The pharmaceutical composition of claim 40 , wherein the dosage form is capsules.43. The pharmaceutical composition of claim 31 , further comprising a pharmaceutically active agent selected from the group consisting of dronabinol claim 31 , granisetron claim 31 , metoclopramide claim 31 , ondansetron claim 31 , and prochlorperazine claim 31 , and a pharmaceutically acceptable salt thereof.44. A method of treating nausea in a subject in need thereof claim 43 , the method comprising administering to the subject an effective amount of the pharmaceutical composition of .451. A method of treating cancer in a subject in need thereof claim 43 , the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim claim 43 , wherein the ...

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Номер записи: 65
08-03-2018 дата публикации

RUTHENIUM POLYMERISATION CATALYSTS

Номер: US20180065914A1
Автор: Cazin Catherine
Принадлежит:

Cis and trans ruthenium complexes that can be used as catalysts for ring opening metathesis polymerisation (ROMP) are described. The complexes are generally square pyramidal in nature, having two anionic ligands X. Corresponding cationic complexes where one or both of the anionic ligands X are replaced by a non-co-ordinating anionic ligand are also described. Polymers such as polydicyclopentadiene (PDCPD) can be prepared using the catalysts. 3. The method according to wherein the group A is an N-heterocyclic carbene.4. The method according to wherein the anionic ligands X are independently selected from the group consisting of halogen claim 1 , benzoate claim 1 , C-Ccarboxylates.5. The method according to wherein the groups Rand Rare H and aryl.6. The method according to wherein the groups Rand Rare fused to form a substituted or unsubstituted indenylidene moiety.8. The method according to wherein the anionic ligands X are independently selected from the group consisting pivalate claim 1 , trifluoroacetate claim 1 , C-Calkoxy claim 1 , phenoxy claim 1 , C-Calkyl thio claim 1 , tosylate claim 1 , mesylate claim 1 , brosylate claim 1 , trifluoromethane sulfonate claim 1 , phenylacetate claim 1 , and pseudo-halogen.10. The method according to wherein the groups Rand Rare fused together to form a ring that may be substituted or unsubstituted claim 9 , saturated or unsaturated and may be fused to a further ring.11. The method according to wherein the groups Rand Rare fused to form a substituted or unsubstituted indenylidene moiety.12. The method according to wherein the group A is an N-heterocyclic carbene.14. The method according to wherein Rand Rare aryl.15. The method according to wherein Rand Rare phenyl.16. The method according to wherein Ris selected from the group consisting of substituted or unsubstituted primary alkyl and substituted or unsubstituted aryl.16. The method according to wherein Ris methyl claim 9 , ethyl or phenyl.17. The method of claim 1 , further ...

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Номер записи: 66
08-03-2018 дата публикации

Manufacture of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol

Номер: US20180065984A1
Автор: DE FAVERI Carla, Huber Florian Anton Martin
Принадлежит: H. Lundbeck A/S

The present invention relates to a process for synthesis of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol abbreviated THIP, having the INN name gaboxadol, starting from pyrrolidin-2-one. The process comprises a new direct process to obtain the intermediate dimethyl 5-hydroxy-3,6-dihydropyridine-1,4(2H)-5 dicarboxylate or the intermediate diethyl 5-hydroxy-3,6-dihydropyridine-1,4(2H)-dicarboxylate. 127-. (canceled)29. The process according to claim 28 , wherein step (e) is carried out in toluene.30. The process according to claim 28 , wherein the reaction in step (e) is carried out at either a reflux temperature or at a temperature between 70° C. and 85° C.33. The process according to claim 31 , wherein the steps (b) claim 31 , (c) and (d) are carried out in toluene.34. The process according to claim 31 , wherein the base used in step (b) is triethylamine.35. The process according to claim 31 , wherein the compound of formula V is purified by washing with acidified water or by distillation or by a combination of these two purification strategies.36. The process according to claim 31 , wherein the compound of formula V is purified by thin-film distillation.39. The process according to claim 38 , wherein the compound of formula IIb is obtained by a one-pot synthesis. The present invention relates to a process for synthesis of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol abbreviated THIP, having the INN name gaboxadol, starting from pyrrolidin-2-one. The process comprises a new direct process to obtain the intermediate dimethyl 5-hydroxy-3,6-dihydropyridine-1,4(2H)-dicarboxylate or the intermediate diethyl 5-hydroxy-3,6-dihydropyridine-1,4(2H)-dicarboxylate.The compound 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol abbreviated THIP, having the INN name gaboxadol, was disclosed for the first time in EP Patent No. 0000338 and has the molecular structure depicted below.Gaboxadol is a GABAA receptor agonist with functional selectivity for the delta containing GABAA ...

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Номер записи: 67
09-03-2017 дата публикации

2-Amino-3,5,5-Trifluoro-3,4,5,6-Tetrahydropyridines as BACE1 Inhibitors for Treatment of Alzheimer's Disease

Номер: US20170066741A1
Автор: Jensen Thomas, Juhl Karsten, Marigo Mauro, Tagmose Lena
Принадлежит: H. Lundbeck A/S

The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Aβ deposits is beneficial such as Alzheimer's disease. 3. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein Ris CH.4. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein Ris F or H.5. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein Ris CH.6. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein Ar is optionally substituted with one or more F claim 1 , C claim 1 , CN claim 1 , C-Calkyl claim 1 , C-Cfluoroalkyl or C-Calkoxy.7. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the stereochemistry of said compound is (2R claim 1 ,5S) claim 1 , or a.8. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is selected from the group consisting of:(1) N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-fluoropicolinamide;(2) N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-fluoropicolinamide;(3) N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-chloropicolinamide;(4) N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-cyanopicolinamide;(5) N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide;(6) N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-1-(difluoromethyl)-1H-pyrazole-3-carboxamide; and(7) N-(3-((2R,5S)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-2-methyloxazole-4-carboxamide.9. The ...

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Номер записи: 68
11-03-2021 дата публикации

Reagents and Methods for Analysis of Proteins and Metabolites Targeted by Covalent Probes

Номер: US20210072254A1
Автор: Adelmant Guillaume, Ficarro Scott B, Marto Jarrod A
Принадлежит:

The present application relates to mass spectrometry methods for use in identifying proteins or other biomolecules which are bound irreversibly by test compounds. 1. An analytical method , comprising:i) contacting a broad thiol reactive compound with a polypeptide to form a broad thiol reactive compound-polypeptide conjugate;ii) analyzing the broad thiol reactive compound-polypeptide conjugate using a mass spectrometry assay;iii) detecting one or more thiolated ions of the broad thiol reactive compound, or derivative ions thereof, produced in the mass spectrometry assay; andiv) identifying that the broad thiol reactive compound forms an irreversible bond with the polypeptide based on the detection of the one or more thiolated ions, or derivative ions thereof, in the mass spectrometry assay;wherein the thiolated ions or derivatives thereof are fragment ions.2. The method of claim 1 , wherein the compound-polypeptide conjugate comprises one or more thioether bonds between the compound and the polypeptide.3. The method of claim 1 , wherein the irreversible bond is an irreversible covalent bond.4. The method of claim 1 , wherein step i) comprises contacting the compound and the polypeptide in the presence of a first solvent component.5. The method of claim 1 , wherein step i) further comprises contacting the compound and the polypeptide in the presence of a buffer agent.6. The method of claim 1 , wherein step i) is performed using a molar excess of the compound compared to the polypeptide.7. The method of claim 1 , further comprising contacting the broad thiol reactive compound-polypeptide conjugate with an acid in the presence of a second solvent component prior to performing the mass spectrometry assay of step ii).8. The method of claim 1 , wherein the method further comprises digesting the broad thiol reactive compound-polypeptide conjugate prior to the performing the mass spectrometry assay of step ii).9. The method of claim 8 , wherein the digesting comprises ...

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Номер записи: 69
15-03-2018 дата публикации

SELECTIVE FKBP51 LIGANDS FOR TREATMENT OF PSYCHIATRIC DISORDERS

Номер: US20180072667A1
Автор: Bracher Andreas, Feng Xixi, Gaali Steffen, Hausch Felix, Kirschner Alexander, Ruehter Gerd
Принадлежит:

The present invention relates to compounds having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions. 4. The compound according to selected from the group consisting of:2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-(((S)-1-((S)-2-(3,4,5-trimethoxyphenyl)pent-4-enoyl)pyrrolidine-2-carbonyl)oxy)propyl)phenoxy)acetic acid,A09 (S)-(R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl-1-((S)-3-cyclopropyl-2-(3,4,5-trimethoxyphenyl)propanoyl)pyrrolidine-2-carboxylate,A15 (S)-(R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl-1-((S)-2-((R)-cyclohex-2-en-1-yl)-2-(3,4,5-trimethoxyphenyl)acetyl)pyrrolidine-2-carboxylate, andA21 (S)-(R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl) acetyl)pyrrol-idine-2-carboxylate,5. A method for inhibiting a FK506-binding protein comprising contacting a cell with an effective amount of a compound according to .6. A method for treating a disease comprising administering a therapeutically effective amount of a compound according to to a subject in need thereof claim 1 , wherein the disease is selected from a psychiatric disorder claim 1 , a neurological disorder claim 1 , a metabolic disease claim 1 , cancer claim 1 , a glucocorticoid hyposensitivity syndrome claim 1 , peripheral glucocorticoid resistance claim 1 , an infectious disease claim 1 , alopecia claim 1 , abnormally elevated intraocular pressure claim 1 , macular degeneration claim 1 , oxidative damage to eye tissues claim 1 , vision disorder claim 1 , a sleeping disorder claim 1 , asthma claim 1 , diabetes claim 1 , traumatic brain injury claim 1 , ...

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Номер записи: 70
24-03-2022 дата публикации

N-BENZYL-N-ARYLSULFONAMIDE DERIVATIVE AND PREPARATION AND USE THEREOF

Номер: US20220089555A1
Автор: HU Xiuai, HU Yongzhou, WANG Xiaolu, Ye Qing
Принадлежит: Hangzhou Yirui Pharmaceutical Technology Co., Ltd

The invention provides an N-benzyl-N-arylsulfonamide derivative, which is an N-benzyl-N-arylsulfonamide compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof. The N-benzyl-N-arylsulfonamide derivative is obtained by condensing a substituted nitrobenzene with 5- or 6-membered nitrogen-containing aliphatic heterocycle (the ring B), reducing the nitro group to an amino group, and subjecting the amino group to reductive amination, sulfonamidation; or by subjecting a substituted nitrobenzene to nitro reduction, reductive amination and sulfonamidation, and condensing the resultant intermediate with 5- or 6-membered nitrogen-containing aliphatic heterocycle (the ring B). It has been experimentally demonstrated that the N-benzyl-N-arylsulfonamide derivative of the invention can specifically bind to Kv1.3 potassium channel and inhibit or decrease its activity, and is useful in the treatment of autoimmune diseases caused by abnormal activation of the Kv1.3 potassium channel in human or animals. The invention further provides a medicament or a pharmaceutical composition comprising the N-benzyl-N-arylsulfonamide derivative. 4. The N-benzyl-N-arylsulfonamide derivative according to claim 1 , characterized in that the N-benzyl-N-arylsulfonamide derivative is selected from the group consisting of the following compounds:ethyl 4-(2-cyano-4-((4-fluoro-N-propylphenyl)sulfonamido)phenyl) piperazin-1-formate,ethyl 4-(2-cyano-4-(N-(4-fluorobenzyl)propanesulfonamido)phenyl) piperazin-1-formate,ethyl 4-(2-cyano-4-(N-isobutylphenylsulfonamido)phenyl)piperazin-1-formate,N-(3-cyano-4-(4-hydroxypiperidin-1-yl)phenyl)-N-(4-fluorobenzyl) propane-1-sulfonamide,4-(2-cyano-4-(N-(4-fluorobenzyl)propyl)phenyl)-N,N-dimethyl piperazin-1-formamide,ethyl 4-(4-(N-benzylpropanesulfonamido)2-cyanophenyl)piperazin-1-formate,ethyl 4-(2-cyano-4-(N-(3-fluorobenzyl)propanesulfonamido)phenyl) piperazin-1-formate,ethyl 4-(4-(4-(N-(4-chlorobenzyl)propanesulfonamido)2- ...

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Номер записи: 71
05-06-2014 дата публикации

SUBSTITUTED TETRACYCLINE COMPOUNDS

Номер: US20140155357A1
Автор: Abato Paul, Assefa Haregewein, Berniac Joel, Bhatia Beena, Bowser Todd, Chen Jackson, Grier Mark, Honeyman Laura, Ismail Mohamed Y., Nelson Mark L., Ohemeng Kwasi, Pan Jingwen
Принадлежит:

The present invention pertains, at least in part, to novel substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for tetracycline compounds such as blocking tetracycline efflux and modulation of gene expression. 133-. (canceled)3565-. (canceled)66. The compound of claim 34 , wherein Ris methoxycarbonyl substituted alkynyl claim 34 , pyrazinyl claim 34 , methoxymethyl claim 34 , cyclopropyl claim 34 , methyl claim 34 , methoxymethyl substituted alkynyl claim 34 , amino substituted pyridinyl claim 34 , alkylcarbonyl claim 34 , arylcarbonyl claim 34 , pyrimidinyl claim 34 , oxazolyl claim 34 , pyrazolyl claim 34 , carboxylate claim 34 , pyridinyl claim 34 , thiazolyl claim 34 , substituted or unsubstituted thiophenyl claim 34 , piperidinylcarbonyl claim 34 , dialkylaminomethyl claim 34 , cyano claim 34 , substituted or unsubstituted arylthiocarbonyl claim 34 , deuterated alkylaminoalkyl claim 34 , substituted furanyl claim 34 , isoxolazolyl claim 34 , cyano substituted pyridinyl claim 34 , alkylcarbonylamino substituted pyridinyl claim 34 , dialkylamino substituted phenyl claim 34 , pyrrolidonylcarbonyl claim 34 , azepanylcarbonyl claim 34 , carboxylatecarbonyl claim 34 , alkylcarbonyl substituted phenyl claim 34 , aminocarbonyl substituted phenyl claim 34 , carboxylate substituted phenyl or piperazinylcarbonyl.6778-. (canceled)80258-. (canceled)259. A method for treating a tetracycline responsive state in a subject claim 34 , comprising administering to said subject an effective amount of a tetracycline compound of claim 34 , such that said subject is treated.260. The method of claim 259 , wherein said tetracycline responsive state is malaria.261. The method of claim 259 , wherein said tetracycline responsive state is a bacterial infection claim 259 , a viral infection claim 259 , or a parasitic infection. ...

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Номер записи: 72
14-03-2019 дата публикации

FUCOSIDASE INHIBITORS

Номер: US20190077756A1
Автор: Isbell Sara Louise, Ko Amanda Anne, Zankel Todd C.
Принадлежит: HORIZON ORPHAN LLC

The present disclosure relates, in general, to compounds useful as inhibitors of fucosidase enzymes, and to methods and compositions for the treatment of tumors or cancers, such as liver disorders and liver tumors (e.g., hepatocellular carcinoma), with a compound as disclosed herein. 118-. (canceled)20. (canceled)21. The method of claim 19 , wherein the compound reduces tumor metastasis in a subject.2223-. (canceled)24. The method of claim 19 , wherein the treatment results in a decrease in tumor size in the subject.25. The method of claim 19 , wherein the treatment results in a reduction of alpha-fetoprotein levels in blood of the subject compared to levels before treatment.26. The method of claim 19 , wherein the compound is administered intravenously.27. The method of claim 26 , wherein the compound is administered via the hepatic artery.28. The method of claim 19 , wherein the compound is administered in combination with a second agent.29. The method of claim 28 , wherein the second agent is selected from the group consisting of a chemotherapeutic agent claim 28 , a cytotoxic agent claim 28 , a radioisotope claim 28 , an anti-viral agent claim 28 , an anti-fungal agent claim 28 , an anti-inflammatory agent and an antibody.30. The method of claim 29 , wherein the chemotherapeutic agent is selected from the group consisting of doxorubicin and 5-fluorouracil.31. The method of claim 29 , wherein the second agent is a cytotoxic agent.32. The method of claim 31 , wherein the cytotoxic agent is selected from the group consisting of mechlorethamine hydrochloride claim 31 , cyclophosphamide claim 31 , ifosfamide claim 31 , chlorambucil claim 31 , melphalan claim 31 , busulfan claim 31 , thiotepa claim 31 , carmustine claim 31 , lomustine claim 31 , dacarbazine and streptozocin.33. The method of claim 29 , wherein the second agent is a radioisotope.34. The method of claim 33 , wherein the radioisotope is selected from the group consisting of I claim 33 , I claim 33 , In ...

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Номер записи: 73
14-03-2019 дата публикации

4-CYANO-BENZYL CARBAMIMIDOYLCARBAMATE DERIVATIVES AND THEIR USE AS AOC3 INHIBITORS

Номер: US20190077790A1
Автор: BLUM Andreas, Himmelsbach Frank, Peters Stefan
Принадлежит:

The invention relates to new benzonitrile derivatives of the formula (I) wherein Rto Rand A are as defined in the description and Claims, to their medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them. 5. The compound according to claim 3 , wherein Ris selected from the group consisting of: [{'sup': 4', 'N', 'N', 'N', 'N', 'N, 'sub': 2', '3', '1-3', '1-3', '2', '1-3', '1-4', '2', '2', '1-3', '2', '1-3', '2', '2', '2', '1-3', '1-3, 'wherein each Ris optionally substituted with one or more groups independently of each other selected from the group consisting of F, Cl, Br, CN, OH, —COH, CF, C-alkyl, C-alkyl-O—, (R)N—, C-alkyl-C(═O)—, C-alkyl-O—C(═O)—, (R)N—C(═O)—, (R)N—C-alkyl-, cyclopropyl-CH—O—, C-alkyl-SO—, (R)N—SO— and C-alkyl-C(═O)—(R)N—C-alkyl-; and'}, {'sub': '2', 'sup': '4', 'wherein a —CH— group of the piperazinyl group of Ris optionally replaced with a —C(═O)— group;'}], '2-oxo-pyrrolidinyl-yl, piperidinyl, piperazinyl, tetrahydropyranyl, 2-oxo-oxazolidin-3-yl, cyclopentyl, phenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, [1,3,5]triazinyl, thiazolyl, imidazo[1,2-a]pyridin-2-yl, oxazolyl and oxadiazolyl,'}or a pharmaceutically acceptable salt thereof.9. A pharmaceutically acceptable salt of a compound according to .10. (canceled)11. A method for treating NASH (non-alcoholic steatohepatitis) claim 1 , retinopathy or nephropathy claim 1 , the method comprising administering a compound according to or a pharmaceutically acceptable salt thereof claim 1 , to a patient in need thereof.12. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable salt thereof claim 1 , optionally together with one or more inert carriers and/or diluents.13. A method for treating a disease or condition which is mediated by inhibiting the activity of AOC3 claim 1 , the method comprising administering to a patient in need thereof a compound according to or a pharmaceutically acceptable salt ...

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Номер записи: 74
22-03-2018 дата публикации

ANTI-PCSK9 COMPOUNDS AND METHODS FOR THE TREATMENT AND/OR PREVENTION OF CARDIOVASCULAR DISEASES

Номер: US20180079730A1
Автор: Abdel-Meguid Sherin Salaheldin, Abou-Gharbia Magid, Blass Benjamin, Childers Wayne, Elshourbagy Nabil, Ghidu Victor, Martinez Rogelio, Meyers Harold, Mousa Shaker A.
Принадлежит:

Disclosed are compounds that modulate the physiological action of the proprotein convertase subtilisin kexin type 9 (PCSK9), and methods of using these modulators to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease (CVD), including treatment of hypercholesterolemia. 8. The method of claim 2 , wherein the compound is selected from the group consisting of [(3-chloro-4-methylphenyl)carbamoyl](phenyl)methyl 4-(carbamoylamino)benzoate (SBC-110 claim 2 ,686); N-(3-chloro-4-methylphenyl)-2-[(4-acetamidophenyl)formamido]-2-phenylacetamide (SBC-110 claim 2 ,720); and [(3-chloro-4-methylphenyl)carbamoyl](phenyl)methyl 4-acetamidobenzoate (SBC-110 claim 2 ,721).9. The method of claim 2 , wherein the compound is N-{4-[4-(4-methylphenyl)-2-phenylpiperazine-1-carbonyl]phenyl}acetamide (SBC-110 claim 2 ,736) or {4-[4-(3-chloro-4-methylphenyl)-2-phenylpiperazine-1-carbonyl]phenyl}urea (SBC-110 claim 2 ,733).10. The method of claim 2 , further comprising administering to said patient a therapeutically effective amount of a low density lipoprotein (LDL) lowering drug.11. The method of claim 10 , wherein said LDL lowering drug is a statin.12. The method of claim 6 , further comprising administering to said patient a therapeutically effective amount of a low density lipoprotein (LDL) lowering drug.13. The method of claim 12 , wherein said LDL lowering drug is a statin. This application claims the benefit of U.S. Provisional Application No. 61/789,867, filed Mar. 15, 2013, the entirety of which is incorporated herein by reference.The present invention was made with support from the National Heart, Lung and Blood Institute (NHLBI) under SBIR Grant No. HL092712. The U.S. Government has certain rights in this invention.The present invention relates to compounds that modulate the physiological action of the proprotein convertase subtilisin kexin type 9 (PCSK9), including its interaction with the low density lipoprotein receptor (LDLR). More ...

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Номер записи: 75
22-03-2018 дата публикации

PROCESS FOR PRODUCING HETEROCYCLIC COMPOUND

Номер: US20180079741A1
Автор: Hirano Sayuri, Tsuruoka Ryoji, YAMADA Masatoshi, Yamano Mitsuhisa
Принадлежит: Takeda Pharmaceuticals Company Limited

The present invention provides a method of efficiently producing an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative. The optically active piperidine-3-carboxamide or a derivative thereof, which is obtained by subjecting 1,4,5,6-tetrahydropyridine-3-carboxamide or a derivative thereof to an asymmetric reduction in the presence of a catalyst, is used as an intermediate. 2. The method according to claim 1 , wherein the organic metal complex is a transition metal complex.3. The method according to claim 2 , wherein the transition metal complex is a ruthenium complex.4. The method according to claim 3 , wherein the ruthenium complex is represented by the formula:{'br': None, 'sup': 'a', 'sub': '2', '[Ru(OCOR)L*]\u2003\u2003(VIII)'}wherein{'sup': 'a', 'sub': '1-3', 'Ris an optionally substituted Calkyl group; and'}{'sup': 'a', 'Lis a diphosphine ligand.'} This application is a divisional of U.S. application Ser. No. 15/125,299, which is the U.S. National Stage application of PCT/JP2015/057541, filed Mar. 13, 2015, which claims priority from Japanese application 2014-052809, filed Mar. 14, 2014.The present invention relates to a production method of an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative which is useful as a dipeptidylpeptidase inhibitor, and various intermediates useful therefor, and production methods thereof.An optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative is known to be useful as a dipeptidylpeptidase inhibitor and an agent for the treatment of diabetes.Patent Document 1 discloses a method of producing a 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative by reacting optically active 3-aminopiperidine with a 6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative.Patent Document 2 discloses a method of efficiently producing an optically active 8-(3-aminopiperidin-1-yl)xanthine derivative by ...

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Номер записи: 76
24-03-2016 дата публикации

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Номер: US20160083348A1
Автор: LI Zhe, Xu Qing
Принадлежит: Global Blood Therapeutics, Inc.

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 4. (canceled)7. The compound of claim 2 , wherein ring B is substituted with 1-3: halo claim 2 , C-Calkyl claim 2 , COR claim 2 , or COOR; and{'sup': '15', 'sub': 1', '6', '6', '10', '1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the C-Calkyl, C-Caryl, 5-10 membered heteroaryl or 4-10 membered heterocyclyl is optionally substituted.'}8. (canceled)10. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .13. A composition comprising a compound of and at least one pharmaceutically acceptable excipient.14. A method for increasing oxygen affinity of hemoglobin S in a subject claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .15. A method for treating oxygen deficiency associated with sickle cell anemia or acute respiratory distress syndrome claim 9 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .16. A method for increasing oxygen affinity of hemoglobin S in a ...

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Номер записи: 77
23-03-2017 дата публикации

PROCESS FOR PRODUCING HETEROCYCLIC COMPOUND

Номер: US20170081305A1
Автор: Hirano Sayuri, Tsuruoka Ryoji, YAMADA Masatoshi, Yamano Mitsuhisa
Принадлежит: Takeda Pharmaceutical Company Limited

The present invention provides a method of efficiently producing an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative. 2. The method according to claim 1 , wherein the organic metal complex is a transition metal complex.3. The method according to claim 2 , wherein the transition metal complex is a ruthenium complex.4. The method according to claim 3 , wherein the ruthenium complex is represented by the formula:{'br': None, 'sup': a', 'a, 'sub': '2', '[Ru(OCOR)L]\u2003\u2003(VIII)'}wherein{'sup': 'a', 'sub': '1-3', 'Ris an optionally substituted Calkyl group; and'}{'sup': 'a', 'Lis a diphosphine ligand.'} The present invention relates to a production method of an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative which is useful as a dipeptidylpeptidase inhibitor, and various intermediates useful therefor, and production methods thereof.An optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative is known to be useful as a dipeptidylpeptidase inhibitor and an agent for the treatment of diabetes.Patent Document 1 discloses a method of producing a 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative by reacting optically active 3-aminopiperidine with a 6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative.Patent Document 2 discloses a method of efficiently producing an optically active 8-(3-aminopiperidin-1-yl)xanthine derivative by subjecting racemic 3-aminopiperidine to acylation with phthalic anhydride, subjecting the obtained 3-phthalimide piperidine to optical resolution with optically active tartaric acid, coupling the obtained optically resolved compound with a xanthine ring, and subjecting the obtained compound to deacylation.Patent Document 3 discloses a method of optically resolving racemic piperidine-3-carboxamide with optically active lactic acid.Patent Document 4 discloses a method of producing an optically ...

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Номер записи: 78
26-03-2015 дата публикации

Trans-2-decenoic acid derivative and drug containing same

Номер: US20150087823A1
Автор: Kunihiko Higashiura, Mitsuru Naiki, Munekazu Iinuma, Shoei Furukawa, Tomonori Matsumoto
Принадлежит: Nagoya Industrial Science Research Institute, Nippon Zoki Pharmaceutical Co Ltd

The present invention relates to a novel trans-2-decenoic acid derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical agent containing the compound as an active ingredient. The trans-2-decenoic acid derivative or a pharmaceutically acceptable salt, which is the compound of the present invention, is specifically represented by the general formula (I): wherein X is a substituent such as a 1-pyrrolidyl, a 3-thiazolizyl, or a piperidino, and the compound is highly useful as a pharmaceutical agent, such as a prophylactic or therapeutic agent for a peripheral nerve disorder induced by administration of an anticancer agent, a prophylactic or therapeutic agent for neurodegenerative diseases or mental diseases such as dementia, Alzheimer's disease, Parkinson's disease, diabetic neuropathy, depression, glaucoma, or autistic disorder spectrum, a therapeutic or repairing agent for spinal cord injury, analgesics against various pain diseases, or the like.

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Номер записи: 79
12-06-2014 дата публикации

Histone deacetylase inhibitors and compositions and methods of use thereof

Номер: US20140163009A1
Автор: Alen F Haughan, Andrew J Stott, Celia Dominguez, Christopher A Luckhurst, Ignacio Muñoz-Sanjuan, Perla Breccia, Roland W Burli, Samantha J Hughes
Принадлежит: CHDI Foundation Inc

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

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Номер записи: 80
12-03-2020 дата публикации

2-(SUBSTITUTED BENZENE MATRIX) AROMATIC FORMATE FTO INHIBITOR, PREPARATION METHOD THEREFOR, AND APPLICATIONS THEREOF

Номер: US20200079727A1
Автор: Dong Ze, Huang Yue, XU Hongjiao, YANG Caiguang, Zhang Tao
Принадлежит:

The invention provides 2-(substituted phenylhetero) aromatic formate FTO inhibitors, a preparation method thereof, and applications thereof. Specifically, disclosed in the present invention are a 2-(substituted phenylhetero) aromatic formate compound represented by the following formula (I), and a pharmaceutically acceptable salt, a hydrate or a solvate thereof, which can be used as an FTO targeting inhibitor for treating diseases associated with FTO targets, including obesity, metabolic syndrome (MS), type 2 diabetes (T2D), Alzheimer's diseases, and cancers such as breast cancers, small-cell lung cancers, human bone marrow rhabdomyosarcoma, pancreatic cancer, malignant glioblastoma and the like. 5. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , and Ris independently selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , OH claim 1 , methyl and methoxy.6. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof claim 1 , wherein each of Aand Ais independently CR′.8. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof claim 1 , wherein the pharmaceutically acceptable salt is selected from the group consisting of inorganic acid salts claim 1 , organic acid salts claim 1 , inorganic alkali salts claim 1 , and organic base salts.9. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof claim 1 , wherein the pharmaceutically acceptable salt is alkali metal salts.10. (canceled)11. (canceled)12. A pharmaceutical composition claim 1 , which comprises: (i) a therapeutically effective amount of the compound of formula (I) of claim 1 , or the pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof claim 1 ...

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Номер записи: 81
12-03-2020 дата публикации

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

Номер: US20200079732A1
Автор: LI Zhe, Xu Qing
Принадлежит:

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation. 2. (canceled)3. The compound of claim 1 ,{'sub': 2', '2', '2, 'wherein Y—Z is —CHO— or —CHCH—.'}4. The compound of claim 3 , wherein Ris C-Calkoxy.6. (canceled)7. The compound of claim 1 , wherein ring B is substituted with 1-3substituents selected from halo claim 1 , C-Calkyl claim 1 , COR claim 1 , and COOR; and{'sup': '15', 'sub': 1', '6', '6', '10, 'Ris C-Calkyl, C-Caryl, 5-10 membered heteroaryl or a 4-10 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein the alkyl, aryl, heteroaryl or heterocyclyl is optionally substituted.'}8. (canceled)9. (canceled)10. A composition comprising a compound of claim 1 , and at least one pharmaceutically acceptable excipient.11. A method for increasing oxygen affinity of hemoglobin S in a subject claim 1 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .12. A method for treating sickle cell disease claim 2 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of . This application is a continuation of U.S. application Ser. No. 15/688,185, filed Aug. 28, 2017, which is a continuation of U.S. application Ser. No. 14/836,869, filed Aug. 26, 2015, now U.S. Pat. No. 9,776,960, which is a continuation of U.S. application Ser. No. 14/599,341, filed Jan. 16, 2015, which is a continuation of U.S. application Ser. No. 13/815,735, filed Mar. 15, 2013, now U.S. Pat. No. 8,952,171, which are incorporated herein by reference in their entirety.This invention provides compounds and pharmaceutical compositions ...

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Номер записи: 82
29-03-2018 дата публикации

EBNA1 INHIBITORS AND THEIR METHOD OF USE

Номер: US20180086699A1
Автор: Lieberman Paul M., McDonnell Mark E., Messick Troy E., Reitz Allen B., Smith Garry R., Velvadapu Venkata, Zhang Yan
Принадлежит:

Pharmaceutical compositions of the invention comprise EBNA1 inhibitors useful for the treatment of diseases caused by EBNA1 activity such as cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis. Pharmaceutical compositions of the invention also comprise EBNA1 inhibitors useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection. Pharmaceutical compositions of the invention also comprise EBNA1 inhibitors useful for the treatment of diseases caused by lytic Epstein-Barr Virus (EBV) infection. 4. The method of claim 1 , wherein the compound is at least one selected from the group consisting of:3-{2-[3-(methylsulfamoyl)phenyl]ethynyl}-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indol-3-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(3-methanesulfonamidophenyl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;2-(1H-pyrrol-1-yl)-3-[2-(3-sulfamoylphenyl)ethynyl]benzoic acid;3-[2-(3-carbamoylphenyl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-6-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(2-hydroxypyridin-4-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indazol-6-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-{2-[3-(3,3-dimethyl-2-oxoazetidin-1-yl)phenyl]ethynyl}-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{3-[(2-carboxy-2,2-dimethylethyl)amino]phenyl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyrazin-3-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-3-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;3-(2-{imidazo[1,2-a]pyridin-5-yl}ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid;2-(1H-pyrrol-1-yl)-3-(2-{1H-pyrrolo[2,3-b]pyridin-5-yl}ethynyl)benzoic acid;3-[2-(1-methyl-1H-indol-4-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1-methyl-1H-indol-5-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1-benzothiophen-6-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-[2-(1H-indol-7-yl)ethynyl]-2-(1H-pyrrol-1-yl)benzoic acid;3-{2-[2-( ...

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Номер записи: 83
29-03-2018 дата публикации

TETRAHYDROPYRIDINE DERIVATIVES AND THEIR USE AS ANTIBACTERIAL AGENTS

Номер: US20180086709A1
Автор: CHO Chong-Hwan, Choi Ji-hoon, Choi Sun-Ho, Choi Sung-Hak, Im Weon-Bin, KIM Jin-Hyuk, KIM Yoon-Jung, Lee Hyung-Keun, LEE Min-Jung, Moon Ho-Sang, Moon Jun-Hwan, Park Cheon-Hyoung, PARK Jung-Sang, SONG Seung-Hyun, Sung Hyun-Jung
Принадлежит:

The present disclosure relates to a novel tetrahydropyridine derivative compound, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, methods for preparing the compounds, methods for inhibiting UDP-3-O—(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC), methods for treating Gram-negative bacterial infections, the use of the compounds for the preparation of therapeutic medicaments for treating Gram-negative bacterial infections, and pharmaceutical compositions for prevention or treatment of Gram-negative bacterial infections, which contain the compounds. The compounds represented by formula I, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present disclosure can exhibit excellent effects on the treatment bacterial infections. 2. The tetrahydropyridine compound claim 1 , a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to :wherein,n is 1 or 2;{'sub': '1', 'Ris C1-C6 alkyl;'}{'sub': '2', 'Ris C1-C6 alkyl;'}{'sub': '3', 'Ris hydrogen;'}L is aryl, heteroaryl or null, wherein at least one H of aryl or heteroaryl may be substituted with halogen, C1-C6 alkyl or C1-C6 haloalkyl;D is C≡C or null;E is C≡C or null;G is C1-C6 alkyl, C3-C7 cycloalkyl, 4-6 membered heterocycloalkyl, aryl or heteroaryl,{'sub': A', 'B', 'C, 'wherein at least one H of C1-C6 alkyl may be substituted with halogen, —NRR, —OH or —OR,'}{'sub': '2', 'at least one H of 4-6 membered heterocycloalkyl may be substituted with C1-C6 alkyl, —(C═O)—C1-C6 alkyl or —S(═O)—C1-C6 alkyl,'}{'sub': A', 'B', 'A', 'B', 'C', '2', '2', 'A', 'B, 'at least one H of aryl or heteroaryl may be substituted with C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 alkyl-NRR, halogen, nitro, cyano, —NRR, —OH, —OR, —S(═O)—C1-C6 alkyl or —S(═O)—NRR;'}{'sub': A', 'B', 'A', 'B, 'Rand Rare each independently hydrogen or C1-C6 alkyl, or Rand Rmay be linked together to form 4-6 membered ring, wherein the 4-6 membered ring may have O atom and at least one H ...

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Номер записи: 84
19-06-2014 дата публикации

New Complexes of Ruthenium, Method for Their Preparation, and Their Application in Olefin Metathesis Reactions

Номер: US20140171607A1
Автор: BARBASIEWICZ Michal, GRELA Karol, Michalak Michal
Принадлежит: UMICORE AG & CO. KG

The present invention provides new ruthenium complexes of Formula (1), which contain a chelate ring created by a halogen atom X. The invention concerns also a method for the preparation of the new ruthenium complexes and their application in metathesis reactions. 5. The method according to claim 4 , wherein the reaction is carried out in the presence of anhydrous halogen salts of copper(I) such as CuBr or CuCl in the presence of Brønsted acids such as HSO claim 4 , HCl claim 4 , HNO claim 4 , HPO claim 4 , sulphonated polymers (Nafion-H) claim 4 , or other acids bonded with a fixed substrate claim 4 , in a solvent.6. Method The method according to claim 4 , wherein the reaction is carried out at a temperature in the range of 0-120° C.7. The method according to claim 4 , wherein the reaction is carried out in a protic or aprotic solvent or a chlorinated solvent or in an aromatic hydrocarbon solvent claim 4 , or in mixtures thereof.8. The method according to claim 4 , wherein the reaction is carried out in a solvent such as methylene chloride and/or toluene.9. A method of using the ruthenium complexes of formula 1 comprising using the ruthenium complexes as (pre)catalysts in metathesis processes.10. The method according to claim 9 , wherein the ruthenium complexes are used as (pre)catalysts in ring-opening metathesis reactions claim 9 , homometathesis claim 9 , cross-metathesis claim 9 , metathesis of the alkene-alkyne (ene-yne) type claim 9 , ring-closing metathesis or ROMP-type polymerisation reactions. The invention concerns new ruthenium complexes which act as (pre)catalysts, a method for their preparation, and their application in olefin metathesis reactions. This invention is used in organic synthesis in a broad sense.In applications of olefin metathesis in organic synthesis, significant progress has been made in recent years. In the state of the art, a number of carbene complexes of ruthenium are known which act as (pre)catalysts and which display both high ...

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Номер записи: 85
05-04-2018 дата публикации

PROCESSES OF MAKING AND CRYSTALLINE FORMS OF A MDM2 INHIBITOR

Номер: US20180092898A1
Автор: BIO Matthew, Caille Sebastien, COCHRAN Brian, FANG Yuanqing, FOX Brian M., Lucas Brian S., McGee Lawrence R., VOUNATSOS Filisaty, WIEDEMANN Sean H., WORTMAN Sarah
Принадлежит: Amgen Inc.

The present invention provides processes for making 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid as well as intermediates and processes for making the intermediates. Also provided are crystalline forms of the compound and the intermediates. 14. The process of wherein the dehydrating conditions are azeotropic distillation with toluene.19. The process of wherein the oxidation is accomplished using ozone.20. The process of wherein the oxidation is accomplished using ozone followed by Pinnick oxidation.25. The process of wherein the base is sodium tert-butoxide.26. The process of wherein the oxidation is accomplished using RuCland NaIO.38. The process of wherein the oxidizing agent is ozone and the acid is hydrochloric acid. The present invention provides processes for making 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (“Compound A” herein) as well as intermediates and processes for making the intermediates. Also provided are crystalline forms of the compound and the intermediates.p53 is a tumor suppressor and transcription factor that responds to cellular stress by activating the transcription of numerous genes involved in cell cycle arrest, apoptosis, senescence, and DNA repair. Unlike normal cells, which have infrequent cause for p53 activation, tumor cells are under constant cellular stress from various insults including hypoxia and pro-apoptotic oncogene activation. Thus, there is a strong selective advantage for inactivation of the p53 pathway in tumors, and it has been proposed that eliminating p53 function may be a prerequisite for tumor survival. In support of this notion, three groups of investigators have used mouse models to demonstrate that absence of p53 function is a continuous requirement for the maintenance of established tumors. When the investigators restored ...

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Номер записи: 86
09-04-2015 дата публикации

Carboxamide compounds and their use as calpain inhibitors

Номер: US20150099786A1
Автор: Achim Moeller, Andreas Kling, Charles W. Hutchins, Helmut Mack, Katja Jantos, Wilfried Hornberger
Принадлежит: AbbVie Deutschland GmbH and Co KG, AbbVie Inc

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R 1 , R 2 , R 3a , R 3b , R 4 , Q, Y, A and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula Ia and Ib in which R 1 , r, R 2b , R 3a , R 3b , R 4 , Y and X have the meanings mentioned in the claims, including the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y is a moiety CH 2 —CH 2 , CH 2 —CH 2 —CH 2 , N(R y# )—CH 2 , N(R y# )—CH 2 —CH 2 or CH═CH—CH═, each optionally having 1 or 2 H-atoms replaced with identical or different radicals R y , wherein R y and R y# have the meanings mentioned in the claims.

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Номер записи: 87
01-04-2021 дата публикации

METHOD OF INHIBITING TAU PHOSPHORYLATION

Номер: US20210095248A1
Автор: Burns Barbier Lindsay, Wang Hoau-Yan
Принадлежит:

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. - 168.-. (canceled)70. The method according to claim 69 , wherein said compound or a pharmaceutically acceptable salt thereof is present dissolved or dispersed in a pharmaceutically acceptable diluent as a pharmaceutical composition when administered.85. The method according to claim 69 , wherein said administration is carried out a plurality of times.86. The method according to claim 85 , wherein said administration is carried out daily.87. The method according to claim 85 , wherein said administration is carried out multiple times daily.88. The method according to claim 70 , wherein said pharmaceutical composition is in liquid form.89. The method according to claim 70 , wherein said pharmaceutical composition is in solid form. This application is a continuation of application Ser. No. 16/030,494 of the same title filed on Jul. 9, 2018 that is now U.S. Pat. No. 10,760,052, that itself was a division of application Ser. No. 13/940,016 of the same title filed on Jul. 11, 2013 and is now U.S. Pat. No. 10,017,736, which claims priority from application Ser. No. 61/789,180 that was filed on Mar. 15, 2013, and application Ser. No. 61/671,235 that was filed on Jul. 13, 2012, whose disclosures are incorporated herein by reference.The present invention contemplates a method of central nervous system (CNS) treatment to inhibit the formation of hyperphosphorylated tau protein and the use of a contemplated compound in the manufacture of a medicament for inhibiting tau protein hyperphosphorylation that can lead to pathological formation of ...

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Номер записи: 88
26-03-2020 дата публикации

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

Номер: US20200095205A1
Автор: Berlin Michael, CREW Andrew P., Crews Craig M., Dong Hanqing, Hornberger Keith R., Snyder Lawrence B., Wang Jing, Zimmermann Kurt
Принадлежит:

The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor. 134.-. (canceled)40. The method of claim 35 , wherein the composition further comprises an effective amount of at least one additional anti-cancer agent.41. The method of claim 36 , wherein the composition further comprises an effective amount of at least one additional anti-cancer agent.42. The method of claim 37 , wherein the composition further comprises an effective amount of at least one additional anti-cancer agent.43. The method of claim 38 , wherein the composition further comprises an effective amount of at least one additional anti-cancer agent.44. The method of claim 39 , wherein the composition further comprises an effective amount of at least one additional anti-cancer agent.45. The method of claim 40 , wherein the anti-cancer agent is estramustine claim 40 , docetaxel claim 40 , ketoconazole claim 40 , goserelin claim 40 , histrelin claim 40 , triptorelin claim 40 , buserelin claim 40 , cyproterone claim 40 , flutamide claim 40 , bicalutamide claim 40 , nilutamide claim 40 , pamidronate claim 40 , or zolendronate.46. The method of claim 41 , wherein the anti-cancer agent is estramustine claim 41 , docetaxel claim 41 , ketoconazole claim 41 , goserelin claim 41 , histrelin claim 41 , triptorelin claim 41 , buserelin claim 41 , cyproterone claim 41 , flutamide claim 41 , bicalutamide claim 41 , ...

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Номер записи: 89
12-04-2018 дата публикации

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

Номер: US20180099940A1
Автор: Berlin Michael, CREW Andrew P., Crews Craig M., Dong Hanqing, Hornberger Keith R., Snyder Lawrence B., Wang Jing, Zimmermann Kurt
Принадлежит:

The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor. 4. The compound of claim 1 , wherein the CLM comprises a chemical group derived from an imide claim 1 , a thioimide claim 1 , an amide claim 1 , or a thioamide that binds to the cereblon E3 ubiquitin ligase.5. The compound of claim 4 , wherein the chemical group is a phthalimido group claim 4 , or an analog or derivative thereof.6. The compound of claim 1 , wherein the CLM is thalidomide claim 1 , lenalidomide claim 1 , pomalidomide claim 1 , analogs thereof claim 1 , isosteres thereof claim 1 , or derivatives thereof.12. The bifunctional compound of claim 9 , wherein CLM comprises a chemical group derived from an imide claim 9 , a thioimide claim 9 , an amide claim 9 , or a thioamide that binds cereblon E3 ubiquitin ligase.13. The bifunctional compound of claim 12 , wherein the chemical group is a phthalimido group claim 12 , or an analog or derivative thereof.14. The bifunctional compound of claim 9 , wherein the CLM is thalidomide claim 9 , lenalidomide claim 9 , pomalidomide claim 9 , analogs thereof claim 9 , isosteres thereof claim 9 , or derivatives thereof.21. The bifunctional compound according to claim 9 , wherein L is a polyethylene group optionally substituted with aryl or phenyl comprising from 1 to 10 ethylene glycol units.22. The bifunctional compound according to claim 9 , wherein the compound ...

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Номер записи: 90
04-04-2019 дата публикации

NANO-TO-NANO FE/PPM Pd CATALYSIS OF CROSS-COUPLING REACTIONS IN WATER

Номер: US20190099747A1
Автор: Handa Sachin, Lipshutz Bruce H.
Принадлежит:

In one embodiment, the present application discloses a catalyst composition comprising: a) a reaction solvent or a reaction medium; b) organometallic nanoparticles comprising: i) a nanoparticle (NP) catalyst, prepared by a reduction of an iron salt in an organic solvent, wherein the catalyst comprises at least one other metal selected from the group consisting of Pd, Pt, Au, Ni, Co, Cu, Mn, Rh, Ir, Ru and Os or mixtures thereof; c) a ligand; and d) a surfactant; wherein the metal or mixtures thereof is present in less than or equal to 50,000 ppm relative to the iron salt. 120.-. (canceled)22. The method of claim 21 , wherein the metal claim 21 , other than Pd claim 21 , is selected from the group consisting of Pt claim 21 , Au claim 21 , Ni claim 21 , Co claim 21 , Cu claim 21 , Mn claim 21 , Rh claim 21 , Ir claim 21 , Ru and Os or a mixture thereof.23. The method of further comprising:iii) contacting the product mixture with an organic solvent to form an organic phase and an aqueous phase; andiv) separating the organic phase from the aqueous phase containing the micelle composition as well as the iron/ppm Pd nanoparticles.24. The method of further comprising:v) re-cycling the aqueous phase containing the micelle composition and Fe/ppm Pd nanoparticles for use in a subsequent cross coupling or other reactions.25. The method of claim 21 , wherein the reaction solvent is water claim 21 , and the reaction solvent further comprising an organic solvent claim 21 , wherein the organic co-solvent is present in at least 5% claim 21 , 10% claim 21 , 20% claim 21 , 30% claim 21 , 40% claim 21 , 50% claim 21 , 70% claim 21 , 80% or at least 90% wt/wt.2611. The method of claim claim 21 , wherein the organic co-solvent is present at a wt of organic co-solvent to the wt of water (wt/wt) of 1/10 claim 21 , 2/10 claim 21 , 5/10 claim 21 , 10/10 claim 21 , 20/10 claim 21 , 30/10 claim 21 , 50/10 claim 21 , 70/10 claim 21 , 90/10 claim 21 , 100/10 claim 21 , 200/10 claim 21 , 300/10 ...

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Номер записи: 91
21-04-2016 дата публикации

Novel bis-Benzylidine Piperidone Proteasome Inhibitor with Anticancer Activity

Номер: US20160106725A1
Автор: Balasubramanyam Karanam, Ravi K. Anchoori, Richard B. Roden
Принадлежит: JOHNS HOPKINS UNIVERSITY

We describe a bis-benzylidine piperidone, RA190, which covalently binds to the ubiquitin receptor RPN13 (ADRM1) in the 19S regulatory particle and inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma lines, even those resistant to bortezomib, were sensitive to RA190 via ER stress-related apoptosis. RA190 stabilized targets of human papillomavirus (HPV) E6 oncoprotein, and preferentially killed HPV-transformed cells. After p.o. or i.p. dosing of mice, RA190 distributed to plasma and major organs excepting brain, and potently inhibited proteasome function in skin and muscle. RA190 administration i.p. profoundly reduced growth of multiple myeloma and ovarian cancer xenografts, and oral RA190 treatment retarded HPV+ syngeneic mouse tumor growth, without impacting spontaneous HPV-specific CD8+ T cell responses, suggesting its therapeutic potential. The bis-benzylidine piperidone RA190 is a new orally-available proteasome inhibitor. Multiple myeloma, cervical and ovarian cancers are particularly sensitive to RA190.

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Номер записи: 92
02-06-2022 дата публикации

Piperidinone Derivatives as MDM2 Inhibitors for the Treatment of Cancer

Номер: US20220169611A1
Автор: BARTBERGER Michael D., BECK Hilary Plake, Chen Xiaoqi, Connors Richard Victor, Deignan Jeffrey, Dequette, EKSTEROWICZ John, FISHER BENJAMIN, FOX Brian M., FU Jiasheng, FU Zice, GONZALEZ BUENROSTRO Ana, Gonzalez Lopez De Turiso Felix, Gribble Michael W., Gustin Darin J., Heath Julie A., HUANG Xin, I Jason A., JIAO XianYun, Johnson Michael G., KAYSER Frank, Kopecky David John, LAI SuJen, LI Yihong, LI Zhihong, Liu Jiwen, Low Jonathan D., Lucas Brian S., Ma Zhihua, McGee Lawrence R., McIntosh Josel, MCMINN Dustin L., MEDINA Julio C., Mihalic Jeffrey Thomas, OLSON Steven H., Rew Yossup, ROVETO Philip M., SUN Daqing, Wang Xiaodong, WANG Yingcai, YAN Xuelei, Yu Ming, ZHU Jiang
Принадлежит:

The present invention provides MDM2 inhibitor compounds of Formula I, 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —C(H)RR claim 1 , —NRR claim 1 , phenyl or pyridine claim 1 , wherein the phenyl or the pyridyl substituted with one or more Ras allowed by valence.12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof claim 11 , wherein Re is H or methyl or ethyl.14. The compound of claim 13 , or a pharmaceutically acceptable salt thereof claim 13 , wherein Re is H or methyl or ethyl.19. A compound claim 13 , or a pharmaceutically acceptable salt thereof claim 13 , selected from:2-((3R,5R,6S)-1-((S)-1-tert-butoxy-1-oxobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)acetic acid;2-((3S,5R,6S)-1-((S)-1-tert-butoxy-1-oxobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-1-oxobutan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-4-methyl-1-oxopentan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-1-oxopentan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3S,5S,6R)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((R)-1-ethoxy-1-oxopentan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-1-((S)-2-tert-Butoxy-1-cyclopropyl-2-oxoethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-cyclopropyl-2-hydroxyethyl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-methoxybutan-2-yl)-2-oxopiperidin-3-yl)acetic acid;2-((3R,5R,6S)-5-( ...

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Номер записи: 93
02-06-2022 дата публикации

CHEMICAL PROCESS FOR PREPARING PHENYLPIPERIDINYL INDOLE DERIVATIVES

Номер: US20220169630A1
Автор: Fu Peng, Gai Yu, Gao Feng, KONG Weiyong, LU Yadong, MARTIN Benjamin, MIN Zhongcheng, RONG Shaofeng, Shu Chutian, Wang Can, WANG Ruidong, ZHAO Jibin, ZHAO Xianglin, Zhao Yi, ZHOU Jianguang
Принадлежит:

The present invention relates to a method of synthesizing a compound of formula (I) also referred to as 4-(((2S,4S)-(4-ethoxy-1-(((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl))benzoic acid, or a pharmaceutically acceptable salt thereof, and/or intermediates thereof, their use as pharmaceuticals and pharmaceutical compositions and the use of intermediates for preparing a compound of formula (I), or a pharmaceutically acceptable salt thereof. 116-. (canceled)18. The process of claim 17 , wherein the Lewis acid is selected from the group consisting of MgCl claim 17 , MgBr claim 17 , and MgIor mixtures thereof.19. The process of claim 17 , wherein the base is selected from the group consisting of N claim 17 ,N-diisopropylethylamine claim 17 , 1 claim 17 ,8-diazabicyclo[5.4.0]undec-7-ene claim 17 , 1 claim 17 ,4-diazabicyclo[2.2.2]octane claim 17 , or mixtures thereof.20. The process of claim 17 , wherein the aldehyde source is selected from the group consisting of formaldehyde claim 17 , paraformaldehyde claim 17 , and 2 claim 17 ,4 claim 17 ,6-trimethyl-1 claim 17 ,3 claim 17 ,5-trioxane.21. The process of claim 17 , wherein Pis selected from the group consisting of tert-butyloxycarbonyl (Boc) claim 17 , toluenesulfonyl (tosyl) claim 17 , and trifluoromethanesulfonyl.23. The process of claim 22 , wherein the Lewis acid is selected from the group consisting of MgCl claim 22 , MgBr claim 22 , and MgIor mixtures thereof.24. The process of claim 22 , wherein the base is selected from the group consisting of N claim 22 ,N-diisopropylethylamine claim 22 , 1 claim 22 ,8-diazabicyclo[5.4.0]undec-7-ene claim 22 , 1 claim 22 ,4-diazabicyclo[2.2.2]octane claim 22 , or mixtures thereof.25. The process of claim 22 , wherein the aldehyde source is selected from the group consisting of formaldehyde claim 22 , paraformaldehyde claim 22 , and 2 claim 22 ,4 claim 22 ,6-trimethyl-1 claim 22 ,3 claim 22 ,5-trioxane.26. The process of claim 22 , wherein Pis selected from the ...

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Номер записи: 94
23-04-2015 дата публикации

PROCESS FOR MAKING CGRP RECEPTOR ANTAGONISTS

Номер: US20150112067A1
Автор: Andreani Teresa, Chen Frank, Lynch Joseph, Molinaro Carmela, Wuelfing W. Peter, Yasuda Nobuyushi, YIN Jianguo, Zhong Yong-Li
Принадлежит:

The disclosure encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, having less steps and improved yields as compared to previous synthetic methods for making these compounds, which are CGRP receptor antagonists, useful for the treatment of migraine. Conditions for an amide bond formation between an acid and amine include for example reacting the compounds of Formulae B (after salt break) and C with an amide coupling reagent and optionally an additive and an acid and/or a base in a non-reactive solvent. 2. The process according to where the compound of Formula B is coupled with a compound of Formula C after salt break by reacting the reagents with an amide coupling reagent in a non-reactive solvent to yield a compound of Formula I.3. The process according to wherein the amide coupling reagent is selected from the group consisting of EDC claim 2 , HATU claim 2 , T3P® and CDI claim 2 , and the non-reactive solvent is an organic/aqueous mixture selected from the group consisting of DCM/water claim 2 , iPAC/water claim 2 , acetonitrile/water claim 2 , acetone/water claim 2 , iPA/water and THF/water.4. The process according to further comprising an amide coupling reagent additive selected from the group consisting of HOBT and HOPO.5. The process according to wherein a salt of a compound of Formula C is coupled to the compound of Formula B.6. The process according to wherein the arylaldehyde derivative is selected from 2-hydroxybenzaldehyde claim 1 , 2-hydroxy-5-nitrobenzaldehyde and 2-hydroxy-3 claim 1 ,5-dichlorobenzaldehyde.8. The process according to wherein the electrophilic alkylating agent is R—OS(O)CFor R—OS(O)F claim 7 , or R—OS(O)R claim 7 , wherein Ris a polyfluorinated one to six membered carbon chain.9. The process according to wherein: Z is t-butyl-O—C(O)— claim 8 , deprotection is effected by reacting the compound of Formula D with a second acid claim 8 , the base is a lithium base claim 8 , the additive is an ...

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Номер записи: 95
03-07-2014 дата публикации

Pyridylphenyl compounds for inflammation and immune-related uses

Номер: US20140187586A1
Автор: Gary Bohnert, Jun Jiang, Junyi Zhang, Shoujun Chen, Yu Xie, ZhiQiang Xia
Принадлежит: Synta Phamaceuticals Corp

The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein Y, L, X 1 , X 2 , Z, R 3 , R 4 , and n are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

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Номер записи: 96
19-04-2018 дата публикации

N1-CYCLIC AMINE-N5-SUBSTITUTED BIGUANIDE DERIVATIVES, METHODS OF PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

Номер: US20180105494A1
Автор: Cho Woong, HEO Hye Jin, KIM Yong Eun, LEE Ji Sun, MIN Chang Hee, OH Byung Kyu, OH Ju Hoon
Принадлежит:

The present invention provides an N1-cyclic amine-N5-substituted biguanide derivative compound represented by Formula 1, a method of preparing the same and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient. The biguanide derivatives have an effect of inhibiting cancer cell proliferation, cancer metastasis and cancer recurrence by activation of AMPK, even when administered in a small dose compared with conventional drugs. 120-. (canceled)22. The compound of Formula 1 or the pharmaceutically acceptable salt thereof of claim 21 , wherein the compound of Formula 1 isN1-(3-methyl)piperidine-N5-(4-fluoro)phenyl biguanide;N1-(3-methyl)piperidine-N5-(4-bromo)phenyl biguanide;N1-(3-methyl)piperidine-N5-(4-chloro,3-trifluoromethyl)phenyl biguanide;N1-(3-methyl)piperidine-N5-(3-fluoro,4-trifluoromethyl)phenyl biguanide;N1-(3-methyl)piperidine-N5-(4-fluoro,3-trifluoromethyl)phenyl biguanide;N1-(2-methyl)piperidine-N5-(4-trifluoromethoxy)phenyl biguanide;N1-(2-methyl)piperidine-N5-(3-trifluoromethoxy)phenyl biguanide;N1-(2-methyl)piperidine-N5-(4-trifluoromethyl)phenyl biguanide;N1-(3-methyl)piperidine-N5-(3-fluoro,4-trifluoromethoxy)phenyl biguanide;N1-(2-methyl)piperidine-N5-(3-fluoro,4-trifluoromethoxy)phenyl biguanide;N1-(2-methyl)piperidine-N5-(4-chloro)phenyl biguanide;N1-(2-methyl)piperidine-N5-(4-fluoro,3-trifluoromethyl)phenyl biguanide;N1-(2-methyl)piperidine-N5-(3-trifluoromethyl)phenyl biguanide;N1-(2-methyl)piperidine-N5-(4-chloro,3-trifluoromethyl)phenyl biguanide;N1-(3-methyl)piperidine-N5-(4-trifluoromethyl)phenyl biguanide;N1-(3-methyl)piperidine-N5-(4-trifluoromethoxy) phenyl biguanide;N1-(3-methyl)piperidine-N5-(3-trifluoromethoxy)phenyl biguanide;N1-(3-methyl)piperidine-N5-(4-fluoro,3-trifluoromethyl)phenyl biguanide;N1-(3-methyl)piperidine-N5-(4-chloro)phenyl biguanide;N1-(3-methyl)piperidine-N5-(3-trifluoromethyl)phenyl biguanide;N1-(2,6-dimethyl)piperidine-N5-(4- ...

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Номер записи: 97
20-04-2017 дата публикации

Novel Cell-Permeable Succinate Compounds

Номер: US20170105961A1
Автор: Eskil Elmer, Karl Henrik Johannes Ehinger, Magnus Joakim HANSSON, Steven Moss
Принадлежит: NEUROVIVE PHARMACEUTICAL AB

The present invention provides novel cell-permeable succinates and cell permeable precursors of succinateaimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.

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Номер записи: 98
29-04-2021 дата публикации

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

Номер: US20210122709A1
Автор: Clark Roger B., Hunt Diana K., Plamondon Louis, Xiao Xiao-Yi, Zahler Robert, Zhou Jingye
Принадлежит:

The present invention is directed to a compound represented by Structural Formula (A): 4. The compound of claim 3 , wherein Ris hydrogen or a (C-C)alkyl.5. The compound of claim 3 , wherein Ris selected from (C-C)alkyl claim 3 , (C-C)cycloalkyl(C-C)alkyl claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , phenyl claim 3 , phenyl(C-C)alkyl claim 3 , (C-C)cycloalkyl and halo(C-C)alkyl claim 3 , wherein each alkyl claim 3 , alkoxy and cycloalkyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl and halo; and each phenyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl claim 3 , halo claim 3 , (C-C)alkoxy claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , —CN claim 3 , halo(C-C)alkyl claim 3 , and halo(C-C)alkoxy.6. The compound of claim 3 , wherein Ris selected from hydrogen claim 3 , methyl and ethyl.7. The compound of claim 6 , wherein Ris selected from the group consisting of cyclopropyl claim 6 , cyclobutyl claim 6 , cyclopentyl claim 6 , cyclopropylmethyl claim 6 , cyclobutylmethyl claim 6 , phenyl claim 6 , benzyl claim 6 , —(CH)—O—CH claim 6 , —(CH)—OCH claim 6 , —C(CH) claim 6 , —CH(CH) claim 6 , —CHC(CH) claim 6 , —CHCH(CH) claim 6 , —CH—CF claim 6 , —(CH)—CHF claim 6 , and —(CH)CH; n is 0 claim 6 , 1 claim 6 , 2 claim 6 , 3 claim 6 , 4 claim 6 , 5 or 6; and wherein the phenyl or benzyl group represented by Ris optionally substituted with one or two substituents independently selected from the group consisting of (C-C)alkyl claim 6 , halogen claim 6 , (C-C)alkoxy claim 6 , (C-C)alkoxy(C-C)alkyl claim 6 , —CN claim 6 , halo(C-C)alkyl claim 6 , and halo(C-C)alkoxy.8. The compound of claim 7 , wherein Ris selected from cyclopropyl claim 7 , cyclopropylmethyl claim 7 , cyclobutyl claim 7 , cyclopentyl claim 7 , cyclohexyl claim 7 , —(CH)—O—CH claim 7 , —C(CH) claim 7 , —CH( ...

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Номер записи: 99
29-04-2021 дата публикации

Method for producing n-alkoxycarbonylpiperidine derivative, and intermediate therefor

Номер: US20210122729A1
Автор: Kiyono Nakagawa, Yoshihiro Ito, Yumiko Tanaka
Принадлежит: Yuki Gosei Kogyo Co Ltd

The object of the present invention is to provide a simple method for preparing an N-alkoxycarbonyl piperidine derivative. The object can be solved by a method for preparing a hydroxypiperidine derivative, comprising a step of: (A) reacting a piperidylidene acetic acid derivative represented by the formula (1): wherein R 1 is an aralkyl group which may have a substituent group, and R 2 is an alkyl group, with 4-hydroxypiperidine in the presence of base, to obtain a hydroxypiperidine derivative represented by the formula (2) or the formula (3): wherein R 1 is an aralkyl group which may have a substituent group.

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Номер записи: 100