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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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Применить Всего найдено 2932. Отображено 100.
18-04-2013 дата публикации

KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME

Номер: US20130096301A1
Автор: Cumming Graham, Edwards Louise G., Forrest Bryan T., Li Sze-Wan, Liu Yong, Patel Narendra Kumar B., Pauls Heinz W., Sampson Peter Brent
Принадлежит: UNIVERSITY HEALTH NETWORK

The present invention is directed to novel synthetic methods for preparing a spiro cyclopropyl indolinone compound represented by Structural Formula (A): (A) or its pharmaceutically acceptable salt thereof. Also included are synthetic intermediates described herein. 2. (canceled)4. The method of claim 3 , wherein Xand Xare —OSOR″ claim 3 , wherein R″ is Calkyl or phenyl optionally substituted one or more substituents independently selected from the group consisting of halogen claim 3 , nitro claim 3 , Calkyl and Calkoxy;{'sub': '1-6', 'the base is an alkali metal hydride, an alkali metal amide, an alkali metal hydroxide, an alkyl alkali metal, an aryl alkali metal or an alkali metal Calkoxide; and'}the reaction is carried out in an aprotic organic solvent.5. (canceled)6. The method of claim 4 , wherein the base is an alkali metal hydride; and the aprotic organic solvent is selected from tetrahydrofuran claim 4 , diethylether claim 4 , dimethoxyethane claim 4 , toluene claim 4 , methylene chloride claim 4 , dimethyl formamide claim 4 , dimethyl sulfoxide claim 4 , acetonitrile claim 4 , dioxane claim 4 , methyl tert-butyl ether claim 4 , 1 claim 4 ,2-dichloroethane claim 4 , or a combination thereof.710-. (canceled)11. The method of claim 6 , wherein:{'sup': 1', 'P', 'P, 'sub': 2', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6, 'Pis —C(═O)O—R, —SO—R, tetrahydro-2H-pyran-2-yl or benzyl optionally substituted one or more substituents independently selected from the group consisting of halogen, nitro, Calkyl, Chaloalkyl, Calkoxy, Chaloalkoxy and (Calkoxy)Calkyl;'}{'sup': 2', 'P', 'P, 'sub': 1-6', '1-6', '1-6', '1-6', '2', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6, 'Pis Calkyl, Chaloalkyl, (Calkoxy)Calkyl, —C(═O)O—R, —SO—R, tetrahydro-2H-pyran-2-yl or benzyl optionally substituted one or more substituents independently selected from the group consisting of halogen, nitro, Calkyl, Chaloalkyl, Calkoxy, Chaloalkoxy, (Calkoxy)Calkyl; and'}{'sup': 'P', 'sub': 1-6', '1-6', '1-6', '1-6 ...

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Номер записи: 1
02-05-2013 дата публикации

HETERO-SUBSTITUTED ACETANILIDE DERIVATIVES AS ANALGESIC AGENTS

Номер: US20130109863A1
Автор: Carson John R., McNally James J.
Принадлежит: Janssen Pharmaceutica N.V.

Hetero-substituted acetanilide derivatives are disclosed as analgesic agents. The compounds of the invention are useful in methods for treating a disease or condition in a mammal characterized by pain and/or fever. 123-. (canceled)251. A compound of claim wherein Rand Rtaken together form an optionally substituted imidazole and enantiomers , diastereomers , tautomers , or pharmaceutically acceptable salts thereof.26. A compound selected from the group consisting of:pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide;5-Methyl-1H-pyrazole-3-carboxylic acid (4-hydroxy-phenyl)-amide; and3H-Imidazole-4-carboxylic acid (4-hydroxy-phenyl)-amide;and enantiomers, diastereomers, tautomers, or pharmaceutically acceptable salts thereof.27. A compound of claim 26 , wherein the compound is pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide and enantiomers claim 26 , diastereomers claim 26 , tautomers claim 26 , or pharmaceutically acceptable salts thereof.28. A compound of claim 26 , wherein the compound is 5-Methyl-1H-pyrazole-3-carboxylic acid (4-hydroxy-phenyl)-amide and enantiomers claim 26 , diastereomers claim 26 , tautomers claim 26 , or pharmaceutically acceptable salts thereof.30. A composition of claim 29 , wherein Rand Rtaken together form an optionally substituted imidazole and enantiomers claim 29 , diastereomers claim 29 , tautomers claim 29 , or pharmaceutically acceptable salts thereof.31. A composition comprising a compound selected from the group consisting of:pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide;5-Methyl-1H-pyrazole-3-carboxylic acid (4-hydroxy-phenyl)-amide; and3H-Imidazole-4-carboxylic acid (4-hydroxy-phenyl)-amide;and enantiomers, diastereomers, tautomers, or pharmaceutically acceptable salts thereof.32. The composition of wherein the compound is pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide and enantiomers claim 31 , diastereomers claim 31 , tautomers claim 31 , or pharmaceutically acceptable salts thereof.33. The composition of ...

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Номер записи: 2
16-05-2013 дата публикации

LONIDAMINE ANALOGUES FOR FERTILITY MANAGEMENT

Номер: US20130123296A1
Автор: Chakrasali Ramappa, Georg Ingrid Gunda, Jakkaraj Sudhakar Rao, Roby Katherine, Tash Joseph S.
Принадлежит: The University of Kansas

Fertility management can include: administering to the subject one or more doses of a compound according to Formula I so as to reduce fertility in the subject. Fertility management can also include administering an effective amount of the compound to: impair Sertoli cell function in a male subject; inhibit spermatogenesis in the subject; reduce testis weight in the subject; reduce ovary weight in a female subject; reduce serum progesterone in the female subject; impair ovarian follicle function in the female subject; causing reversible fertility in the subject. In order to return fertility, the method can include ceasing administration of the compound to the subject so as to return fertility in the subject. The compound can be administered for irreversibly sterilizing the subject. 124.-. (canceled)26. A method as in claim 25 , wherein{'sub': '1', 'wherein Ris carboxyl, acryl, or carboxylic acid hydrazide; and'}{'sub': '2', 'wherein Ris halogen, alcohol, alkoxy, aralkyl, cycloalkyl, haloalkyl, haloalkoxy, amino, or carboxyl.'}27. A method as in claim 25 , wherein{'sub': '1', 'Rincludes one or more of a carboxylic acid, carboxylic acid ester, propionic acid, 2-methyl propionic acid, oxirane-carboxylic acid, cyclopropane carboxylic acid, propionic acid methyl ester, 2-methyl propionic acid methyl ester, oxirane-carboxylic acid methyl ester, or cyclopropane carboxylic acid methyl ester; and/or'}{'sub': '2', 'Rincludes a halogen, haloalkyl, or haloalkoxy.'}28. A method as in claim 25 , wherein the claim 25 , compound is selected from the group consisting of:3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-acrylic acid;6-chloro-1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid hydrazide;1-(2,4-dichlorobenzyl)-6-fluoro-1H-indazole-3-carboxylic acid methyl ester;6-fluoro-1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid hydrazide;3-[1-(2,4-dichlorobenzyl)-6-fluoro-1H-indazol-3-yl]-acrylic acid;3-[1-(2,4-dichlorobenzyl)-6-chloro-1H-indazol-3-yl]-acrylic ...

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Номер записи: 3
23-05-2013 дата публикации

LIGANDS FOR ANTIBODY AND Fc-FUSION PROTEIN PURIFICATION BY AFFINITY CHROMATOGRAPHY

Номер: US20130131321A1
Автор: Arnold Marc, Bittermann Holger, Burkert Klaus, Keil Oliver, Neumann Thomas, Ott Inge, Schmidt Kristina, Schwizer Daniel, Sekul Renate
Принадлежит: GRAFFINITY PHARMACEUTICALS GMBH

The present invention relates to the use for affinity purification of an antibody or an fragment of an antibody, of a ligand-substituted matrix comprising a support material and at least one ligand covalently bonded to the support material, the ligand being represented by formula (I) 2. The use of wherein Aris phenylene claim 1 , preferably methoxy-substituted phenylene.3. The use of wherein the C═O and the NH group are bonded to Arin meta position to each other.4. The use of wherein the 5- or 6-membered heterocyclic aromatic ring of Aris attached to the C═O group via a carbon ring atom which is adjacent to a ring heteroatom claim 1 , preferably a nitrogen or oxygen atom.5. The use of wherein the 5- or 6-membered heterocyclic aromatic ring of Arcontains two or more nitrogen atoms or one or more nitrogen atoms and an oxygen atom.6. The use of wherein the 5- or 6-membered heterocyclic aromatic ring of Aris N-methyl-substituted pyrazole claim 5 , pyridine claim 5 , isoxazole or oxadiazole.7. The use according to wherein the support material comprises a material selected from carbohydrates or crosslinked carbohydrates claim 1 , preferably agarose claim 1 , cellulose claim 1 , dextran claim 1 , starch claim 1 , alginate and carrageenan claim 1 , Sepharose claim 1 , Sephadex; synthetic polymers claim 1 , preferably polystyrene claim 1 , styrene-divinylbenzene copolymers claim 1 , polyacrylates claim 1 , PEG-Polycacrylate copolymers polymethacrylates claim 1 , polyvinyl alcohol claim 1 , polyamides and perfluorocarbons; inorganic materials claim 1 , preferably glass claim 1 , silica and metal oxides; and composite materials.8. The use according to wherein the protein is an antibody claim 1 , preferably an IgG type antibody claim 1 , or an Fc fusion protein.9. The use of wherein the purification is attained by binding of the ligand of the ligand-substituted matrix to an Fc fragment or domain of the antibody or the fusion protein.10. The use according to wherein the Fc ...

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Номер записи: 4
20-06-2013 дата публикации

TRICYCLIC NECROSTATIN COMPOUNDS

Номер: US20130158024A1
Автор: Cuny Gregory D., Degterev Alexei, Hitomi Junichi, Jagtap Prakash, Yuan Junying
Принадлежит:

The present invention features compounds, pharmaceutical compositions, and methods for treating trauma, ischemia, stroke, degenerative diseases associated with cellular necrosis, and other conditions. Screening assays for identifying compounds useful for treating these conditions are also described. 2. The Nec-3 compound of claim 1 , wherein said Nec-3 compound is a substantially pure (3R claim 1 ,3aR)-rel isomer claim 1 ,or a pharmaceutically acceptable salt thereof.3. The Nec-3 compound of claim 2 , wherein Ris —C(O)R claim 2 , and Ris substituted Calkyl claim 2 ,or a pharmaceutically acceptable salt thereof.4. The Nec-3 compound of claim 2 , wherein said Nec-3 compound is a substantially pure (3R claim 2 ,3aR)-enantiomer claim 2 ,or a pharmaceutically acceptable salt thereof.5. The Nec-3 compound of claim 2 , wherein said Nec-3 compound is a substantially pure (3S claim 2 ,3aS)-enantiomer claim 2 ,or a pharmaceutically acceptable salt thereof.6. The Nec-3 compound of claim 2 , wherein{'sub': '2', 'the bond indicated by (a) is a double bond; Z is CH; and'}{'sub': 1', '2', '4', '6', '7', '10', '11, 'each of R, R, R, R, R, R, and R, independently, represents hydrogen,'}or a pharmaceutically acceptable salt thereof.7. The Nec-3 compound of claim 6 , wherein{'sub': '8', 'Ris H,'}or a pharmaceutically acceptable salt thereof.8. The Nec-3 compound of claim 2 , wherein{'sub': 3', '5', '2', '9, 'Rrepresents methoxyl; Rrepresents C(O)CHOH; and Rrepresents alkoxy of one to six carbon atoms,'}a pharmaceutically acceptable salt thereof.10. The Nec-3 compound of claim 9 , wherein said Nec-3 compound is a substantially pure (3R claim 9 ,3aR)-enantiomer claim 9 ,or a pharmaceutically acceptable salt thereof.11. The Nec-3 compound of claim 9 , wherein said Nec-3 compound is a substantially pure (3S claim 9 ,3aS)-enantiomer claim 9 ,or a pharmaceutically acceptable salt thereof.12. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(i) the ...

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Номер записи: 5
11-07-2013 дата публикации

PROCESS FOR MAKING HCV PROTEASE INHIBITORS

Номер: US20130178630A1
Автор: Lukin Kirill A.
Принадлежит: AbbVie Inc.

Efficient processes for making HCV protease inhibitors are described. In one embodiment, the process uses novel idazolide derivatives of vinyl-ACCA. 3. The process of claim 2 , wherein Ris a —CHCH.6. The process of claim 5 , wherein Ris a —CHCH.76. The process according to one of - claims 1 , wherein:Z is O;{'sub': '1', 'Ris phenanthridine;'}{'sub': '2', 'Ris an amino protecting group;'}{'sub': '4', 'Ris vinyl;'}X is H or Cl.8. The process of claim 7 , wherein Ris tert-butyloxycarbonyl.9. The process of claim 1 , wherein said HCV protease inhibitor is BI-201335 claim 1 , TMC-435350 claim 1 , vaniprevir claim 1 , MK-5172 claim 1 , BMS-650032 claim 1 , danoprevir claim 1 , GS-9451 claim 1 , or Compound I.1312. The process according to one of - claims 11 , wherein:Z is O;{'sub': '1', 'Ris phenanthridine;'}{'sub': '2', 'Ris tert-butyloxycarbonyl;'}{'sub': '4', 'Ris vinyl;'}X is H or Cl; and{'sub': 3', '2', '3, 'Ris —CHCH.'} This application claims priority to U.S. Provisional Application Ser. No. 61/585,280 filed Jan. 11, 2012, which is incorporated by reference in its entirety.The present invention relates to processes for making Hepatitis C virus (“HCV”) protease inhibitors.BACKGROUNDHCV is the principal cause of non-A, non-B hepatitis and is an increasingly severe public health problem both in the developed and developing world. It is estimated that the virus infects over 200 million people worldwide, surpassing the number of individuals infected with the human immunodeficiency virus (HIV) by nearly five fold. HCV infected patients, due to the high percentage of individuals inflicted with chronic infections, are at an elevated risk of developing cirrhosis of the liver, subsequent hepatocellular carcinoma and terminal liver disease. HCV is the most prevalent cause of hepatocellular cancer and cause of patients requiring liver transplantations in the western world.The present invention features processes for making HCV protease inhibitors. The HCV protease mediates the ...

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Номер записи: 6
18-07-2013 дата публикации

INDAZOLE COMPOUNDS AND THEIR USES

Номер: US20130184287A1
Автор: Deng Xianming, Gray Nathanael, Zhou Wenjun
Принадлежит: Dana-Farber Cancer Institute, Inc.

The present application relates to therapeutic organic compounds, compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof. 45-. (canceled)713-. (canceled)17. The compound of claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , wherein X is NR.18. The compound of claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , wherein X is a bond.19. (canceled)20. The compound of claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein X is a bond.24. The compound of claim 1 , wherein the compound of Formula I is selected from the compounds listed in Table A claim 1 , or a pharmaceutically acceptable salt thereof.25. A method of treating cancer claim 1 , comprising administering to a subject in need thereof a compound of or a pharmaceutically acceptable salt thereof26. The method of claim 25 , wherein the cancer is selected from the group consisting of adenocarcinoma claim 25 , multiple myeloma claim 25 , chronic myelogenous leukemia claim 25 , pancreatic cancer claim 25 , non- small cell lung cancer claim 25 , lung cancer claim 25 , breast cancer claim 25 , colon cancer claim 25 , ovarian cancer claim 25 , cervical cancer claim 25 , uterine cancer claim 25 , prostate cancer claim 25 , malignant melanoma claim 25 , non-melanoma skin cancers claim 25 , gastrointestinal stromal tumors claim 25 , hematologic tumors claim 25 , hematologic malignancies claim 25 , childhood leukemia claim 25 , childhood lymphomas claim 25 , multiple myeloma claim 25 , Hodgkin's disease claim 25 , lymphomas of lymphocytic origin claim 25 , lymphomas of cutaneous origin claim 25 , acute leukemia claim 25 , chronic leukemia claim 25 , acute lymphoblastic leukemia claim 25 , acute myelocytic leukemia claim 25 , chronic myelocytic leukemia claim 25 , plasma cell neoplasm claim 25 , ...

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Номер записи: 7
25-07-2013 дата публикации

HSP90 INHIBITOR AND PREPARATION METHOD AND USE THEREOF

Номер: US20130190509A1
Автор: Ju Huaiqiang, Lin Wenhui, Qian Chuiwen, Wang Yifei, Xia Min, Xing Guowen, Zhang Meiying, ZHOU XIAOPING
Принадлежит:

Disclosed are an Hsp90 inhibitor and a preparation method and use thereof. The Hsp90 inhibitor is 2-(4-(3-acetylcarnitineacyloxy)cyclohexylamino)-4-(1-(3,6,6-trimethyl-4-oxy-4,5,6,7-tetrahydroindazole))benzamide. The Hsp90 inhibitor has good water solubility and high bioavailability, and can effectively inhibit the proliferation of cancer cells, such as leukemia, cervical cancer, breast cancer, human laryngeal epithelial carcinoma, or malignant melanoma cells. It can also effectively inhibit the activity of herpes simplex virus. The maximal non-toxic concentration of the Hsp90 inhibitor on normal cells is a high, and the Hsp90 inhibitor only has specific inhibition effect on cancer cells. 3. Use of an Hsp90 inhibitor of claim 1 , characterized in that said Hsp90 inhibitor is used to prepare an antitumor or antivirus drug.4. Use of an Hsp90 inhibitor of claim 3 , characterized in that said tumor is leukemia claim 3 , cervical cancer claim 3 , breast cancer claim 3 , human laryngeal epithelial carcinoma claim 3 , or malignant melanoma.5. Use of an Hsp90 inhibitor of claim 3 , characterized in that said virus is herpes simplex virus. 1. Field of the InventionThe present invention relates to the biomedical field, and particularly relates to a novel Hsp90 inhibitor and a preparation method and use thereof.2. Description of Related ArtHeat shock proteins (Hsps) are a class of proteins produced by cells under some stress conditions, such as heat shock, glucose starvation, or pathogenic microorganism infection. They are also widely distributed in normal state cells. Hsps are a family of highly conserved proteins expressed in organisms during evolution, which, as molecular chaperones, are involved in the protection of cells against various stimuli (including cold, hot, anoxia, heavy metal ion, virus infection, etc.). Hsps mainly are involved in folding and transporting nascent peptide chains in cells, and identifying denatured proteins, thus playing a role in regulating cell ...

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Номер записи: 8
22-08-2013 дата публикации

METHOD FOR PRODUCING PYRAZOLINONE SALT

Номер: US20130217890A1
Автор: KOJIO Masao, MIURA Masaya
Принадлежит: Sumitomo Chemical Company, Limited

A salt represented by formula (4) produced via 2. The method according to claim 1 , wherein the second step is a step of reacting the mixture dehydrated in the first step with a compound represented by formula (2) while performing dehydration.3. The method according to claim 2 , wherein the second step is a step of reacting the mixture dehydrated in the first step with a compound represented by formula (2) while adjusting the amount of water contained in the reaction solution in the second step to 0.8 wt % or less.4. The method according to claim 2 , wherein the second step is a step of reacting the mixture dehydrated in the first step with a compound represented by formula (2) while performing azeotropic dehydration under reduced pressure at a temperature in the range of 20 to 100° C.5. The method according to claim 1 , wherein the amount of water contained in the mixture dehydrated in the first step is 0.8 wt % or less.6. The method according to claim 1 , wherein the first step is a step of performing azeotropic dehydration under reduced pressure at a temperature in the range of 20 to 100° C.7. The method according to claim 1 , wherein the alkali metal hydroxide is lithium hydroxide.8. The method according to claim 1 , wherein the hydrocarbon solvent is an aromatic hydrocarbon solvent.9. The method according to claim 1 , wherein the second step is a step of reacting the mixture dehydrated in the first step with a compound represented by formula (2) in the presence of an ether solvent. The present invention relates to a method for producing a pyrazolinone salt.In U.S. Pat. No. 6,294,567, a certain kind of pyrazolinone compound is known to be useful as an active ingredient of a plant disease control agent.U.S. Pat. No. 5,869,684 describes a method for producing a compound represented by formula (1A):The present invention provides a method which is capable of producing a pyrazolinone derivative with excellent yield.The present invention is as described below.<1> A ...

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Номер записи: 9
19-09-2013 дата публикации

INDAZOLE, BENZISOXAZOLE, AND BENZISOTHIAZOLE KINASE INHIBITORS

Номер: US20130245015A1
Автор: Dai Yujia, Davidsen Steven K., Ericsson Anna M., Hartandi Kresna, Ji Zhiqin, Michaelides Michael R.
Принадлежит:

Compounds having the formula 3. The compound of wherein X is O.4. The compound of wherein X is NR.5. The compound of wherein L is CHC(O)NR.6. The compound of wherein L is (CH)N(R)C(O)N(R)(CH).7. The compound of wherein X is O and L is (CH)N(R)C(O)N(R)(CH).8. The compound of selected from the group consisting ofN-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-(3-methylphenyl)urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-[2-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-(2-fluoro-5-methylphenyl)urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-[3-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-(3-methylphenyl)urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-[3-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-(3-chlorophenyl)urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-(2-fluoro-5-methylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-[3-(trifluoromethyl)phenyl]urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-chlorophenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-methylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(2-fluoro-5-methylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3,5-dimethylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-phenoxyphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-bromophenyl)urea;N-(4-{3-amino-7-[2-(4-morpholinyl)ethoxy]-1,2-benzisoxazol-4-yl}phenyl)-N′-[3-( ...

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Номер записи: 10
19-09-2013 дата публикации

HETEROARYL-SUBSTITUTED UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE

Номер: US20130245022A1
Автор: Breitenbucher J. Guy, Chambers Alison L., Hawryluk Natalie A., Jones William M., Keith John M., Merit Jeffrey E., Sierestad Mark J., Tichenor Mark S., Timmons Amy K.
Принадлежит: Janssen Pharmaceutica NV

Certain heteroaryl-substituted piperidinyl and piperazinyl urea compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, insulin resistance, diabetes, osteoporosis, and movement disorders (e.g., multiple sclerosis). 2. A chemical entity as in claim 1 , wherein Aris isoxazolo[5 claim 1 ,4-c]pyridin-3-yl claim 1 , isoxazolo[4 claim 1 ,5-c]pyridin-3-yl claim 1 , imidazo[1 claim 1 ,2-b]pyridazin-3-yl claim 1 , 1H-pyrrolo[2 claim 1 ,3-b]pyridin-5-yl claim 1 , imidazo[1 claim 1 ,2-a]pyridin-5-yl claim 1 , 6-[1 claim 1 ,2 claim 1 ,3]triazol-2-yl-pyridin-3-yl claim 1 , 5-methyl-[1 claim 1 ,3 claim 1 ,4]oxadiazol-2-yl claim 1 , imidazo[1 claim 1 ,2-a]pyrimidin-5-yl claim 1 , 4-[1 claim 1 ,2 claim 1 ,3]triazol-1-yl-phenyl claim 1 , 4-[1 claim 1 ,2 claim 1 ,3]triazol-2-yl-phenyl claim 1 , 2-phenyl-pyrimidin-5-yl claim 1 , isoxazolo[4 claim 1 ,5-b]pyridin-3-yl claim 1 , 1 claim 1 ,3-dimethyl-1H-pyrazolo[3 claim 1 ,4-b]pyridin-5-yl claim 1 , benzooxazol-6-yl claim 1 , or 2-methyl-2H-indazol-4-yl.3. A chemical entity as in claim 1 , wherein Aris isoxazolo[5 claim 1 ,4-c]pyridin-3-yl claim 1 , isoxazolo[4 claim 1 ,5-c]pyridin-3-yl claim 1 , isoxazolo[4 claim 1 ,5-b]pyridin-3-yl claim 1 , imidazo[1 claim 1 ,2-b]pyridin-8-yl claim 1 , imidazo[1 claim 1 ,2-a]pyridin-7-yl claim 1 , imidazo[1 claim 1 ,2-a]pyridin-5-yl claim 1 , imidazo[1 claim 1 ,2-a]pyrimidin-7-yl claim 1 , imidazo[1 claim 1 ,2-a]pyrimidin-5-yl claim 1 , imidazo[1 claim 1 ,2-c]pyrimidin-7-yl.45.-. (canceled)6. A chemical entity as in claim 1 , wherein Aris phenyl claim 1 , substituted with one or two Rmoieties.7. A chemical entity as in claim 6 , wherein each Rmoiety is independently selected from the group consisting of: chloro claim 6 , fluoro claim 6 , ...

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Номер записи: 11
10-10-2013 дата публикации

1-BENZYL-3-HYDROXYMETHYLINDAZOLE DERIVATIVES AND USE THEREOF IN THE TREATMENT OF DISEASES BASED ON THE EXPRESSION OF MCP-1, CX3CR1 AND P40

Номер: US20130267704A1
Автор: CAZZOLLA Nicola, FURLOTTI Guido, GUGLIELMOTTI Angelo, MANGANO Giorgina
Принадлежит: Aziende Chim. Riun. Ang. Franc. A.C.R.A.F. S.p.A.

The present invention relates to novel 1-benzyl-3-hydroxymethylindazole derivatives according to formula (I) described in the claims, and to a pharmaceutical composition comprising them, together with a pharmaceutically acceptable vehicle. In addition, the present invention relates to the use of 1-benzyl-3-hydroxymethylindazole derivatives for the preparation of a pharmaceutical composition that is active in the treatment of diseases based on the expression of MCP-1, CX3CR1 and p40, and to their use in a method for treating or preventing diseases based on the expression of MCP-1, CX3CR1 and p40. 1. (canceled)3. The method according to claim 2 , wherein Xand Xare claim 2 , independently of one another claim 2 , an alkyl group having from 1 to 4 carbon atoms claim 2 , optionally substituted with one or more alkyl groups having from 1 to 3 carbon atoms.4. The method according to claim 2 , wherein Xis selected from the group consisting of a CHgroup claim 2 , a CHCHgroup claim 2 , a C(CH)group claim 2 , and a C(CH)CHgroup claim 2 , and Xis selected from the group consisting of a CHgroup claim 2 , a CHCHgroup claim 2 , and a CHCHCHgroup.5. The method according to claim 2 , wherein the residue A is selected from the group consisting of a σ bond claim 2 , a CHCHgroup claim 2 , a CHCHCHgroup claim 2 , a C(CH)CHgroup claim 2 , a CHCHOCHgroup claim 2 , a CHCHOCHCHgroup claim 2 , and a C(CH)CHOCHgroup claim 2 , and a C(CH)CHOCHCHgroup.6. The method according to claim 2 , wherein Rand R claim 2 , which may be identical or different from each other claim 2 , are a hydrogen atom claim 2 , an alkyl group having from 1 to 3 carbon atoms claim 2 , or together form a 6-membered heterocycle.7. The method according to claim 2 , wherein Rand R claim 2 , which may be identical or different from each other claim 2 , are a hydrogen atom claim 2 , or an alkyl group having from 1 to 3 carbon atoms.8. The method according to claim 2 , wherein Rand R claim 2 , which may be identical or ...

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Номер записи: 12
17-10-2013 дата публикации

VIRAL POLYMERASE INHIBITORS

Номер: US20130274218A1
Автор: Bond Silas, Draffan Alistair George, Halim Rosliana, Harding Michael, Jeynes Tyrone Pieter
Принадлежит: BIOTA SCIENTIFIC MANAGEMENT PTY LTD

The present invention relates to viral polymerase inhibitors of formula (I) or salts, N-oxides, solvates, hydrates, racemates, enantiomers or isomers thereof, processes for their preparation and their use in the treatment of Flaviviridae viral infections such as Hepatitis C virus (HCV) infections. 2. A compound according to wherein Ris an optionally substituted oxetane or azetidine ring.4. A compound according to wherein (CH)is an optionally substituted methylenyl claim 1 , ethylenyl or propylenyl moiety.5. A compound according to selected from the group consisting of:3) 5-cyclopropyl-N-methyl-2-(4-methylphenyl)-6-{(methylsulfonyl)[2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide;4) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl) [3-(oxetan-2-yl)propyl]amino}-2H-indazole-3-carboxamide;5) 5-cyclopropyl-N-methyl-2-(5-methylpyridin-2-yl)-6-{(methylsulfonyl) [2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide;6) 6-{[2-(azetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide;7) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(1-methylazetidin-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;8) 6-{[2-(1-acetylazetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide;9) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(2-methyloxetan-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;10) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide;11) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(3-methyloxetan-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;12) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[(3-methyloxetan-3-yl)methyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;13) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[2-(oxetan-2-yl)ethyl]amino}-2H-indazole-3-carboxamide;14) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-[( ...

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Номер записи: 13
07-11-2013 дата публикации

Aryl Substituted Indoles and Their Use as Blockers of Sodium Channels

Номер: US20130296281A1
Автор: Kyle Donald J., Ni Chiyou, TAFESSE Laykea, Yao Jiangchao
Принадлежит: Purdue Pharma L.P.

The invention relates to aryl and heteroaryl substituted compounds of Formula (I), and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein G, R, and Z-Zare defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain. 2. The compound of claim 1 , wherein Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.3. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.4. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.5. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.6. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.7. The compound of claim 1 , wherein Zis CR claim 1 , Ris A claim 1 , and at least one of Z claim 1 , Z claim 1 , Z claim 1 , and Zis N.8. The compound of with the proviso that when Zis N claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zare CR claim 1 , CR claim 1 , CR claim 1 , and CR claim 1 , respectively claim 1 , G is G claim 1 , wherein r is 0 claim 1 , and Ais optionally substituted heteroaryl claim 1 , then Ris not A.10. The compound of with the proviso that when Z claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zare CR claim 1 , CR claim 1 , CR claim 1 , CR claim 1 , and CR claim 1 , respectively claim 1 , R claim 1 , R claim 1 , and Rare hydrogen claim 1 , Ris A claim 1 , G is G claim 1 , wherein Rand Rare H and Ris haloalkylcarbonyl or optionally substituted arylcarbonyl claim 1 , then Ris other than alkoxycarbonyl.23. The compound of claim 1 , wherein G is G.24. ...

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Номер записи: 14
12-12-2013 дата публикации

MINERALOCORTICOID RECEPTOR ANTAGONISTS

Номер: US20130331419A1
Автор: Beresis Richard, Crespo Alejandro, DeVita Robert J., Lan Ping, LIU Kun, Mal Rudrajit, Ogawa Anthony, Qi Changhe, Shen Dong-Ming, Shen Hong, Shu Min, Sinclair Peter J., Sun Zhongxiang, Tan John Qiang, Vande Bunte Ellen K., Wang Yuguang, Wu Zhicai
Принадлежит:

Disclosed are the compounds of the Formula (I) as well as pharmaceutically acceptable salts thereof, which are useful for treating aldosterone-mediated diseases. The processes for preparing compounds of the Formula (I), the use for the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and the pharmaceutical compositions which comprise compounds of the formula (I) are disclosed too. 3. The compound of wherein Ris H.8. The compound of which is(R)—N-{1-[(2R)-2-(4-chlorophenyl)-1-hydroxybutan-2-yl]-1H-indol-4-yl}methanesulfonamide;N-(1-(1-(4-chlorophenyl)-1-(2-cyanocyclopropyl)propyl)-1H-indazol-4-yl)methanesulfonamide;N-(1-(1-(4-chlorophenyl)-1-(3-ethyl-1,2,4-oxadiazol-5-yl)propyl)-1H-indol-4-yl)methanesulfonamide;N-(1-(2-(4-chlorophenyl)-1-hydroxybutan-2-yl)-1H-indazol-4-yl)methanesulfonamide;N-(1-(1-(4-chlorophenyl)-1-(1-hydroxycyclopropyl)propyl)-1H-indol-4-yl)methanesulfonamide;N-(1-(3-(4-chlorophenyl)-2-hydroxypentan-3-yl)-6-fluoro-1H-indol-4-yl)methanesulfonamide;N-(1-(2-(4-chlorophenyl)-1-hydroxybutan-2-yl)indolin-4-yl)methanesulfonamide;N-{1-[3-(4-chlorophenyl)-2-hydroxypentan-3-yl]-1H-indazol-4-ylmethanesulfonamide;N-(1-(2-amino-3-(4-chlorophenyl)pentan-3-yl)-1H-indol-4-yl)methanesulfonamide;1-(1-(3-(4-chlorophenyl)-2-hydroxy-2-methylpentan-3-yl)-1H-indazol-4-yl)-3-methyl-sulfonylurea;methyl {4-[(methylsulfonyl)amino]-1H-indol-1-yl}(phenyl)acetate;N-(1-(3-(4-chlorophenyl)-2-hydroxy-2-methylpentan-3-yl)-6-fluoro-1H-indol-4-yl)methane sulfonamide;N-(1-(3-(4-chlorophenyl)-2-hydroxy-2-methylpentan-3-yl)-1H-indol-4-yl)methanesulfonamide;N-(1-(3-(4-chlorophenyl)-2-hydroxy-2-methylpentan-3-yl)-1H-indazol-4-yl)methanesulfonamide;N-(1-(2-hydroxy-2-methyl-3-(4-(trifluoromethyl)phenyl)pentan-3-yl)-1H-indazol-4-yl)methanesulfonamide;N-(1-(2-(4-chlorophenyl)-1-methoxybutan-2-yl)-1H-indol-4-yl)methanesulfonamide;N-(1-(3-(4-chlorophenyl)-2-oxopentan-3-yl)-1H-indazol-4-yl)methanesulfonamide;N-(1-(2-hydroxy-3-(4-( ...

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Номер записи: 15
19-12-2013 дата публикации

PYRAZOLO-QUINAZOLINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS

Номер: US20130338148A1
Автор: "DAlessio Roberto", BRASCA Maria Gabriella, Fancelli Daniele, FERGUSON Ron, Panzeri Achille, Pevarello Paolo, Polucci Paolo, Quartieri Francesca, Roletto Fulvia, Traquandi Gabriella, Vianello Paola, Vulpetti Anna
Принадлежит: NERVIANO MEDICAL SCIENCES S.R.L.

Pyrazolo-quinazoline derivatives of formula (Ia) or (Ib) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer. 123.-. (canceled)2829.-. (canceled)30128. A product or kit comprising a compound of formula (Ia) or (Ib) as defined in claim , or pharmaceutical compositions thereof as defined in claim , and one or more chemotherapeutic agents , as a combined preparation for simultaneous , separate or sequential use in anticancer therapy.3132-. (canceled) 1. Field of the InventionThe present invention relates to pyrazolo-quinazoline derivatives, to a process for their preparation, to pharmaceutical compositions comprising them, and to their use as therapeutic agents, particularly in the treatment of cancer and cell proliferation disorders.2. Discussion of the BackgroundSeveral cytotoxic drugs such as, e.g., fluorouracil (5-FU), doxorubicin and camptothecins, damage DNA or affect cellular metabolic pathways and thus cause, in many cases, an indirect block of the cell cycle. Therefore, by producing an irreversible damage to both normal and tumor cells, these agents result in a significant toxicity and side-effects.In this respect, compounds capable of functioning as highly specific antitumor agents by selectively leading to tumor cell arrest and apoptosis, with comparable efficacy but reduced toxicity than the currently available drugs, are desirable.It is well known that progression through the cell cycle is governed by a series of checkpoint controls, otherwise referred to as restriction points, which are regulated by a family of enzymes known as the cyclin-dependent kinases (cdk). In turn, the cdks themselves are regulated at many levels such as, for instance, binding to cyclins.The coordinated ...

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Номер записи: 16
26-12-2013 дата публикации

METHODS OF TREATING CANCER AND OTHER DISORDERS

Номер: US20130345270A1
Автор: Kridel Steven J., Lowther W. Todd, Odens Herman W., Schmitt Jeffrey D.
Принадлежит: Waake Forest University Health Sciences

Active compounds useful for inhibiting fatty acid synthase in a subject in need thereof are described. The active compounds are, in general, a 5-mercapto-1H-Indazole-4,7-dione or an analog thereof. The compounds are useful for treating subjects afflicted with, cancer, obesity, diabetes, a viral infection, a bacterial infection, a fungal infection, or a protozoal infection. 1. A method of reversibly or irreversibly inhibiting fatty acid synthase in a subject in need thereof , comprising administering to said subject an active compound as described herein in a treatment-effective amount; wherein said active compound is an 5-mercapto-1H-Indazole-4 ,7-dione or an analog thereof.2. The method of claim 1 , wherein said subject is afflicted with cancer.3. The method of claim 1 , wherein said subject is afflicted with obesity.4. The method of claim 1 , wherein said subject is afflicted with diabetes5. The method of claim 1 , wherein said subject is afflicted with a viral infection.6. The method of claim 1 , wherein said subject is afflicted with a bacterial infection.7. The method of claim 1 , wherein said subject is afflicted with a fungal infection.8. The method of claim 1 , wherein said subject is afflicted with a protozoal infection.11. (canceled) The present invention concerns methods of treatment, and compounds and compositions useful for carrying out such methods.A first aspect of the present invention is a method of inhibiting fatty acid synthase in a subject in need thereof, comprising administering to said subject an active compound as described herein in a treatment-effective amount. Examples of subjects in need thereof include, but are not limited to, subjects afflicted with cancer, obesity, diabetes, viral infection, bacterial infection, fungal infection or protozoal infection.A second aspect of the present invention is the use of an active compound as described herein for the preparation of a medicament for carrying out a method as described herein, such as ...

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Номер записи: 17
09-01-2014 дата публикации

NITROGEN-CONTAINING SATURATED HETEROCYCLIC COMPOUND

Номер: US20140011807A1
Автор: IIJIMA Toru, Kawaguchi Takayuki, Shen Jingkang, Sugama Hiroshi, XIA Guangxin, XIE Jianshu
Принадлежит:

The present invention provides a nitrogen-containing saturated heterocyclic compound of the formula [I]: 12. A pharmaceutical composition comprising the compound according to .14. A method for the treatment and/or prophylaxis of hypertension claim 1 , cardiac failure claim 1 , diabetic nephropathy and the like claim 1 , comprising administration of the compound according to or the pharmaceutically acceptable salt thereof claim 1 , The present invention relates to nitrogen-containing saturated heterocyclic compounds which are useful as a medicine, especially as a renin inhibitor, pharmaceutically acceptable salts and intermediates thereof.Renin inhibitors are expected as a medicine for the prevention and/or treatment of diseases such as hypertension, heart failure, diabetic nephropathy and the like, and 3,4-substituted piperidine derivatives are disclosed for example (Patent Literature 1). But a morpholine derivative is not described in the literature.Also WO 2008/153182 discloses some morpholine derivatives but they are compounds having a formula I wherein R is a hydrogen atom (Patent Literature 2).Patent Literature 1: WO 06/069788 (US 2009/0312304A)Patent Literature 2: WO 2008/153182 (US 2010/0240644A)The present invention provides novel nitrogen-containing saturated heterocyclic compounds having an excellent activity to inhibit renin.In order to solve the problem, the inventors have extensively studied to find novel nitrogen-containing saturated heterocyclic compounds having an excellent activity to inhibit renin and finally completed the present invention.The present invention is as follows:wherein Ris a cycloalkyl group or a non-substituted alkyl group; Ris 1) an optionally substituted aryl group, 2) an optionally substituted tetrahydronaphthyl group, 3) an optionally substituted naphthylidinyl group, 4) an optionally substituted pyridyl group, 5) an optionally substituted pyrazolopyridyl group, 6) an optionally substituted indolyl group, 7) an optionally ...

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Номер записи: 18
20-02-2014 дата публикации

MODULATORS OF CELLULAR ADHESION

Номер: US20140051675A1
Автор: BARR Kenneth, OSLOB Johan D., SHEN Wang, Zhong Min
Принадлежит: SARcode Bioscience Inc.

The present invention provides compounds having formula (I): 175.-. (canceled)76. A pharmaceutical formulation comprising an LFA-1 antagonist or a pharmaceutically acceptable salt or ester thereof , wherein the formulation is an inhalation formulation.80. The formulation of claim 76 , wherein the compound is present in an amount effective to modulate adhesion between intracellular adhesion molecules (e.g. claim 76 , ICAM-1 claim 76 , -2 and -3) and the leukocyte integrin family of receptors.81. The formulation of claim 76 , wherein the compound is present in an amount effective to antagonize CD11/CD18 receptors associated with leukocytes.82. The formulation of claim 76 , wherein the LFA-1 antagonist is a sodium claim 76 , potassium claim 76 , lithium claim 76 , magnesium claim 76 , or calcium salt.83. The formulation of claim 76 , wherein the formulation is in the form of a powder claim 76 , solution claim 76 , spray claim 76 , or inhalant.84. The formulation of claim 76 , further comprising at least one additional therapeutic agent.85. A method for treatment of an inflammatory or immune related disorder in a subject comprising administering to said subject in need thereof an inhalation formulation comprising an LFA-1 antagonist or a pharmaceutically acceptable salt or ester thereof claim 76 , and a pharmaceutically acceptable excipient.89. The method of claim 85 , wherein the compound is present in an amount effective to modulate adhesion between intracellular adhesion molecules (e.g. claim 85 , ICAM-1 claim 85 , -2 and -3) and the leukocyte integrin family of receptors.90. The method of claim 85 , wherein the compound is present in an amount effective to antagonize CD11/CD18 receptors associated with leukocytes.91. The method of claim 85 , wherein the LFA-1 antagonist is a sodium claim 85 , potassium claim 85 , lithium claim 85 , magnesium claim 85 , or calcium salt.92. The method of claim 85 , wherein the formulation is in the form of a powder claim 85 , solution ...

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Номер записи: 19
20-02-2014 дата публикации

PYRAZOLYL AND PYRIMIDINYL TRICYCLIC ENONES AS ANTIOXIDANT INFLAMMATION MODULATORS

Номер: US20140051739A1
Автор: Anderson Eric, BOLTON Gary L., CAPRATHE Bradley, Jiang Xin, LEE Chitase, ROARK William H., Visnick Melean
Принадлежит:

Disclosed herein are novel antioxidant inflammation modulators, including those of the formula: 1107-. (canceled)109. The compound of claim 108 , wherein Ror Ris alkylor substituted alkyl.110. The compound of claim 109 , wherein Rand Rare alkyl.111. The compound of claim 110 , wherein Rand Rare methyl.112. The compound of claim 108 , wherein Ris hydrogen.113. The compound of claim 108 , wherein Ris arylor substituted aryl.114. The compound of claim 113 , wherein Ris aryl.115. The compound of claim 114 , wherein Ris phenyl.116. The compound of claim 108 , wherein Ris alkylor substituted alkyl.117. The compound of claim 116 , wherein Ris alkyl.118. The compound of claim 117 , wherein Ris t-butyl.119. The compound of claim 108 , wherein carbon atom 10 is in the R configuration.120. The compound of claim 108 , wherein carbon atom 10 is in the S configuration.121. The compound of claim 108 , wherein carbon atom 5 is in the R configuration.122. The compound of claim 108 , wherein carbon atom 5 is in the S configuration.124137-. (canceled)138. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00108', 'claim 108'}, 'a) the compound of ;'}b) an optical isomer of the compound, wherein the optical isomer is the enantiomer of the compound; andc) an excipient.139. The pharmaceutical composition of claim 138 , wherein the ratio of the amount of compound to the amount of optical isomer is approximately 1:1.140. The pharmaceutical composition of claim 138 , wherein the ratio of the amount of compound to the amount of optical isomer is approximately 5:1.141. The pharmaceutical composition of claim 138 , wherein the ratio of the amount of compound to the amount of optical isomer is approximately 10:1.142. The pharmaceutical composition of claim 138 , wherein the ratio of the amount of compound to the amount of optical isomer is approximately 20:1. The present application is a divisional application of co-pending U.S. patent application Ser. No. 13/330,378, filed ...

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Номер записи: 20
20-03-2014 дата публикации

ARYLOAZOL-2-YL CYANOETHYLAMINO COMPOUNDS, METHOD OF MAKING AND METHOD OF USING THEREOF

Номер: US20140080862A1
Автор: Huber Scot Kevin, Jacobs Robert Toms, Le Hir de Fallois Loic Patrick, Lee Hyoung Ik, Soll Mark David, Wilkinson Douglas Edward
Принадлежит:

The present invention relates to novel aryloazol-2-yl-cyanoethylamino derivatives of formula (I): 3. The aryloazol-2-yl-cyanoethylamine of claim 2 , wherein{'sub': 2', '8', '9', '10', '11', '1', '6', '2', '6', '2', '6', '3', '7', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '7', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'R, R, R, Rand Reach, independently of one another, is hydrogen, amino, amido, cyano, nitro, halogen, C-C-alkyl, C-C-alkenyl, C-C-alkynyl, C-C-cycloalkyl, hydroxy-C-C-alkyl, halo-C-C-alkyl, C-C-alkylthio, halo-C-C-alkylthio arylthio, C-C-alkoxy, phenoxy, C-C-alkoxy-C-C-alkoxy, C-C-cycloalkyloxy, halo-C-C-alkoxy, C-C-alkylcarbonyl, halo-C-C-alkylcarbonyl, C-C-alkylsulfinyl, halo-C-C-alkylsulfinyl, C-C-alkylsulfonyl, C-C-alkylamino, di(C-C-alkyl)amino, C-C-alkylcarbonylamino, C-C-alkylamino-C-C-alkoxy, di-C-C-alkylamino-C-C-alkoxy, C-C-alkylamino-C-C-alkyl, di-C-C-alkylamino-C-C-alkyl, amino-C-C-alkyl, formyl, HOC—, C-C-alkyl-OC—, unsubstituted or substituted aryl or unsubstituted or substituted phenoxy, whereby the substituents may each be independent of one another and are selected from the group consisting of cyano, nitro, halogen, C-C-alkyl, halo-C-C-alkyl, C-C-alkylthio, halo-C-C-alkylthio, arylthio, C-C-alkoxy, halo-C-C-alkoxy, C-C-alkylcarbonyl, halo-C-C-alkylcarbonyl, C-C-alkylsulfinyl, halo-C-C-alkylsulfinyl, C-C-alkylsulfonyl and halo-C-C-alkylsulfonyl;'}{'sub': 3', '4', '6, 'R, Rand Rare H;'}{'sub': '5', 'Ris methyl;'}{'sub': 7', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', ...

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Номер записи: 21
07-01-2016 дата публикации

CANNABINERGIC NITRATE ESTERS AND RELATED ANALOGS

Номер: US20160002195A1
Автор: Makriyannis Alexandros, Vemuri Venkata Kiran
Принадлежит:

The present technology relates to novel cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools and/or biomarkers. The novel cannabinergic nitrate ester compounds provide medicaments useful in treating a variety of diseases and medical disorders. 2. (canceled)3. The compound of claim 1 , wherein V is ONO.4. (canceled)5. The compound of claim 4 , wherein Ris ONO claim 4 , alkyl-ONO claim 4 , O-alkyl-ONO claim 4 , O—SO-alkyl-ONO claim 4 , —C(O)O-alkyl-ONO claim 4 , alkyl-C(O)O-alkyl-ONO claim 4 , or alkyl-O-alkyl-ONO.6. The compound of claim 1 , wherein:ring C has one, two or three double bonds, and at least one double bond is at the C8-C9 position, the C9-C10 position, or the C6a-C10a position;{'sub': 3', '2', '3', '2, 'W is C(CH), CH(CH), C═O, or CF;'}Z is O or N; and{'sup': '1', 'sub': 2', '2, 'V is H when Ris a group comprising ONO, or V is ONO.'}7. The compound of claim 1 , wherein Y—R—V is ONO claim 1 , alkyl-ONO claim 1 , O-alkyl-ONO claim 1 , O—SO-alkyl-ONO claim 1 , —C(O)O-alkyl-ONO claim 1 , alkyl-C(O)O-alkyl-ONO claim 1 , or alkyl-O-alkyl-ONO.89-. (canceled)11. The compound of claim 1 , wherein:ring C has one double bond at the C8-C9 position or the C9-C10 position;{'sub': 3', '2, 'W is C(CH);'}X is carbon;{'sup': '1', 'Ris H, alkyl, COOH, alkyl-OH;'}{'sup': '2', 'sub': 2', '2, 'Ris OH, O-alkyl, SH, O(CO)alkyl, OC(O)NH, OC(O)NHalkyl, or OC(O)N(alkyl);'}Z is O;{'sub': 3', '2', '2, 'Y is alkyl, C(CH), or CF; and'}{'sub': '2', 'V is ONO.'}12. (canceled)13. The compound of claim 1 , wherein:ring C is saturated;{'sub': 3', '2, 'W is C(CH);'}{'sup': 1', '1, 'X is CH, Ris OH, or X—Ris C═O;'}{'sup': '2', 'Ris OH, O-alkyl, SH, O(CO)alkyl, O(CO)N—'}Z is O{'sub': 3', '2', '2, 'Y is alkyl, C(CH), or CF;'}{'sub': '2', 'V is ONO.'}1517-. (canceled)18. The compound of claim 14 , wherein:ring C is an aromatic ring;ring A is an aromatic ring;ring G is a bond, C═O, NH ...

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Номер записи: 22
07-01-2016 дата публикации

INTERMEDIATES FOR USE IN THE PREPARATION OF INDAZOLE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF

Номер: US20160002210A1
Автор: Eary Todd C., Hache Bruno P., Juengst Derrick, Spencer Stacey Renee, STENGEL Peter J., Watson Daniel John
Принадлежит: ARRAY BIOPHARMA INC.

Provided herein are novel processes for preparing a compound of Formula (I) to the use of said compound as an intermediate in novel processes for the synthesis of indazole derivatives, and to indazole intermediates and derivatives prepared by the processes described herein. 3. The process of claim 2 , wherein about two equivalents of 2 claim 2 ,5-difluorobenzonitrile are used.4. The process of claim 3 , wherein said base in step (a1) is an alkali metal carbonate claim 3 , an alkali metal hydride or an alkali metal bicarbonate.5. The process according to claim 4 , wherein about 1.05 to about 1.2 equivalents of 2-hydrazinylethanol are used.6. The process according to claim 5 , wherein the base in step (a) is an alkali metal carbonate claim 5 , an alkali metal phosphate claim 5 , an alkali metal hydride claim 5 , an alkali metal alkoxide claim 5 , or an alkali metal hydroxide.7. The process according to claim 7 , wherein the transition metal catalyst is a copper claim 7 , platinum claim 7 , palladium claim 7 , iron claim 7 , nickel claim 7 , ruthenium or rhodium catalyst.8. The process according to claim 7 , wherein the transition metal catalyst is a copper catalyst.9. The process according to claim 8 , wherein the copper catalyst is CuCO.Cu(OH) claim 8 , CuI claim 8 , CuO claim 8 , CuBr claim 8 , CuCO claim 8 , CuCl or CuO.10. The process according to claim 9 , wherein the copper catalyst is CuCO—Cu(OH).11. The process according to claim 10 , wherein the reaction is performed in the absence of a diamine ligand.12. The process according to claim 11 , wherein about 0.20 to 0.25 equivalents of the transition metal catalyst is used.13. The process according to claim 12 , wherein the nitrile group of compound (3) is reduced under catalytic hydrogenation conditions.14. The process of claim 13 , wherein said catalytic hydrogenation conditions comprise treating compound (3) with a Raney nickel catalyst in the presence of ammonia and hydrogen.15. The process of claim 14 , ...

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Номер записи: 23
13-01-2022 дата публикации

METHODS AND INTERMEDIATES FOR PREPARING THERAPEUTIC COMPOUNDS

Номер: US20220009904A1
Автор: "OKeefe Brian Michael", Allan Kevin McCormack, Brizgys Gediminas, Dhar Sachin, Doxsee Ian James, GOLDBERG Alex, Heumann Lars V., Huang Zilin, Kadunce Nathaniel Thomas, Kazerani Shahrokh, Lew Willard, Ngo Vinh Xuan, Rainey Trevor James, Roberts Benjamin James, Shi Bing, Steinhuebel Dietrich P., Tse Winston C., Vandehey Amanda Lynn, Wagner Anna Michelle, Wang Xianghong, Wolckenhauer Scott Alan, Wong Chloe Yuyi, Zhang Jennifer R.
Принадлежит:

The present disclosure relates to methods and intermediates useful for preparing a compound of formula I. 1171.-. (canceled)173174.-. (canceled)175. The process of claim 172 , wherein HX is N-Boc-D-leucine or (−)-N-acetyl-D-leucine.176. (canceled)177. The process of claim 172 , wherein the solvent is selected from the group consisting of n-heptane claim 172 , ethyl acetate claim 172 , butyl acetate claim 172 , isobutylacetate claim 172 , diethyl ether claim 172 , methyl tert-butyl ether claim 172 , tetrahydrofuran claim 172 , 2-methyltetrahydrofuran claim 172 , 1 claim 172 ,4-dioxane claim 172 , benzene claim 172 , xylenes claim 172 , toluene claim 172 , dichloromethane claim 172 , dichloroethane claim 172 , chloroform claim 172 , methanol claim 172 , ethanol claim 172 , 2-propanol claim 172 , acetone claim 172 , methyl ethyl ketone claim 172 , methylisobutylketone claim 172 , N claim 172 ,N-dimethylformamide claim 172 , N claim 172 ,N-dimethylacetamide claim 172 , N-methylpyrrolidone claim 172 , dimethylsulfoxide claim 172 , acetonitrile claim 172 , propionitrile claim 172 , butyronitrile claim 172 , water claim 172 , and combinations thereof.178. The process of claim 172 , wherein the solvent is toluene.179180.-. (canceled)181. The process of claim 172 , wherein the compound of formula X is treated with a base selected from the group consisting of potassium hydroxide claim 172 , potassium carbonate claim 172 , potassium bicarbonate claim 172 , sodium carbonate claim 172 , sodium bicarbonate claim 172 , triethylamine claim 172 , ammonium hydroxide claim 172 , potassium phosphate dibasic claim 172 , potassium phosphate tribasic claim 172 , sodium phosphate dibasic claim 172 , and sodium phosphate tribasic in a first solvent selected from the group consisting of diethyl ether claim 172 , methyl tert-butyl ether claim 172 , 2-methyltetrahydrofuran claim 172 , tetrahydrofuran claim 172 , 1 claim 172 ,4-dioxane claim 172 , aromatic solvents claim 172 , dichloromethane ...

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Номер записи: 24
01-01-2015 дата публикации

Substituted 4,5-Dihydro-2H-Benzo[e]Indazole-9-Carboxylates For The Treatment Of Diabetes And Related Disorders

Номер: US20150005357A1
Автор: Goel Atul, Jaiswal Natasha, Rahuja Neha, Rawat Arun Kumar, Srivastava Arvind Kumar, Tamrakar Akhilesh Kumar, Taneja Gaurav
Принадлежит: COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

The present invention relates to the development of novel substituted 4,5-dihydro-2H-benzo[e]indazole-9-carboxylates, which can be used as therapeutic agents for the treatment and prevention of metabolic disorders, and a process of preparing said novel compounds. More particularly, the present invention relates to substituted 4,5-dihydro-2H-benzo[e]indazole-9-carboxylates and their related compounds, processes for preparing the said compounds and to their use in the treatment of diabetes and related metabolic disorders. 2. Compounds as claimed in wherein the representative compounds of the general formula I are;i. Methyl 6-(4-bromophenyl)-8-(methylthio)-2-phenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (1)ii. Methyl 6-(4-chlorophenyl)-8-(methylthio)-2-phenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (2)iii. Methyl 6-(4-methoxyphenyl)-8-(methylthio)-2-phenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (3)iv. Methyl 8-(methylthio)-2,6-diphenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (4)v. Methyl 8-(methylthio)-2-phenyl-6-p-tolyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (5)vi. Methyl 8-(methylthio)-6-(naphthalen-1-yl)-2-phenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (6)vii. Methyl 8-(methylthio)-2-phenyl-6-(thiophen-2-yl)-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (7)viii. methyl 6-(4-fluorophenyl)-8-(methylthio)-2-phenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (8)ix. methyl 8-(methylthio)-2-phenyl-6-(pyren-1-yl)-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (9)x. methyl 6-(4-fluorophenyl)-8-(methylsulfonyl)-2-phenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (10)xi. methyl 8-(methylsulfonyl)-6-(naphthalen-1-yl)-2-phenyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (11)xii. methyl 8-(methylsulfonyl)-2-phenyl-6-(p-tolyl)-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (12)xiii. Methyl 5-(methylthio)-7-(naphthalen-2-yl)-2-phenyl-2,8-dihydroindeno[2,1-c]pyrazole-4-carboxylate (13)3. A compound as claimed in wherein the compounds are ...

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Номер записи: 25
01-01-2015 дата публикации

NOVEL RUTHENIUM CATALYSTS AND THEIR USE FOR ASYMMETRIC REDUCTION OF KETONES

Номер: US20150005500A1
Автор: HADDAD Nizar, LEE Heewon, QU Bo, RODRIGUEZ Sonia, SENANAYAKE Chris Hugh
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Disclosed are novel ruthenium compounds of formula (Ia) and (Ib): 2. The compound of formula (Ia) or (Ib) according to claim 1 , wherein Ris —H.3. The compound of formula (Ia) or (Ib) according to claim 1 , wherein Ris —CH.4. The compound of formula (Ia) or (Ib) according to claim 1 , wherein Ris —OCH.5. The compound of formula (Ia) or (Ib) according to claim 1 , wherein the diamine ligand is compound 4.6. The compound of formula (Ia) or (Ib) according to claim 1 , wherein the diamine ligand is compound 5.7. The compound of formula (Ia) or (Ib) according to claim 1 , wherein the diamine ligand is compound 6.8. The compound of formula (Ia) or (Ib) according to claim 1 , wherein the diamine ligand is compound 7.9. The compound of formula (Ia) or (Ib) according to claim 1 , wherein the diamine ligand is compound 9.10. The compound of formula (Ia) or (Ib) according to claim 1 , wherein the diamine ligand is compound 12.11. The compound of formula (Ia) or (Ib) according to claim 1 , wherein Ris —OCH.12. The compound of formula (Ia) or (Ib) according to claim 1 , wherein the diamine ligand is compound 8.13. The compound of formula (Ia) or (Ib) according to claim 12 , wherein Ris —H.14. The compound of formula (Ia) or (Ib) according to claim 12 , wherein Ris —CH.15. The compound of formula (Ia) or (Ib) according to claim 12 , wherein Ris —OCH.16. The compound of formula (Ia) according to .17. The compound of formula (Ib) according to . The invention relates to a new family of amine-tunable ruthenium catalysts based on chiral bisdihydrobenzooxaphosphole ligands (BIBOP ligands). The catalysts are useful for asymmetric hydrogenation and transfer hydrogenation of a variety of highly challenging ketones, including heteroaryl cyclic ketones.Asymmetric reduction of ketones is a key transformation in the pharmaceutical industry for the preparation of enantiomerically pure alcohols, particularly those bearing heterocycles (see, e.g., (Eds.: J. G. De Vries, C. J. Elsevier), Willey- ...

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Номер записи: 26
14-01-2021 дата публикации

BICYCLIC COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER

Номер: US20210008046A1
Автор: BRAVO Yalda, BURCH Jason David, Chen Austin Chih-Yu, NAGAMIZO Joe Fred
Принадлежит:

The present disclosure is directed to novel compounds of Formula I and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of cancer, including glioblastoma, bone cancer, head and neck cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, adenocarcinoma, oral cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, bladder cancer, hepatocellular carcinoma, renal cell carcinoma, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, and prostate cancer. The compounds of the disclosure are selective antagonists of the EP4 receptor and useful treatment of various diseases that may be ameliorated with blockade of PGE2-mediated signaling. 2. A compound of wherein Ar is aryl or heteroaryl optionally substituted with 1 to 3 substituents independently selected from:(a) halogen,(b) cyano,{'sub': 1', '6, '(c) C-Calkyl,'}{'sub': '5', '(d) SF,'}{'sub': 1', '6, '(e) C-Chaloalkyl,'}{'sup': b', 'b, 'sub': 1', '6', '3', '6', '1', '6, '(f) ORwherein Ris C-Calkyl, aryl, heteroaryl, C-Ccycloalkyl or C-Chaloalkyl;'}(g) heterocycle,(h) aryl, and(i) heteroaryl.3. A compound of or wherein Ar is phenyl.4. A compound any one of to wherein each of X claim 1 , X claim 1 , X claim 1 , Xand Xis independently C—R claim 1 , or one of X claim 1 , X claim 1 , X claim 1 , Xand Xis N claim 1 , and the others are each independently C—R.5. A compound of wherein each of X claim 4 , X claim 4 , X claim 4 , Xand Xis independently C—R.6. A compound of any of to wherein Ris H or a halogen atom.7. A compound of any of to wherein W is selected from the group consisting of:{'sub': '2', '(a) COH; and'}(b) 1H-tetrazole.8. A compound of any of to wherein Z is —CH—.9. A compound of any of to wherein Y is a bond or —CH—.10. A compound of any of to wherein Rand ...

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Номер записи: 27
14-01-2021 дата публикации

SULFONYLDIAZOLES AND N-(FLUOROSULFONYL)AZOLES, AND METHODS OF MAKING THE SAME

Номер: US20210009529A1
Автор: JOHNSON Martin Reid
Принадлежит: Trinapco, Inc.

The present disclosure provides methods for producing N-(fluorosulfonyl)azoles, sulfonyldiazoles, or related derivatives thereof, and the related products including N-(fluorosulfonyl)azoles, sulfonyldiazoles, and related derivatives thereof. For example, an N-(fluorosulfonyl)azole is obtained by reaction of sulfuryl fluoride with an azoles, an azolate salt, an N-silylazole, or a combination thereof. Symmetric and asymmetric sulfonyldiazoles are obtained by further reaction of such an N-(fluorosulfonyl)azole with azoles, azolate salts, or N-silylazoles. A sulfonyldiazole can be also produced by reacting sulfuryl fluoride with an azole, an N-silylazole, or a combination thereof in one pot. 1. A method , comprising:{'sub': 2', '2, 'reacting sulfuryl fluoride (SOF) with an azole or an azolate salt having a first azole base structure (Azole 1), wherein Azole 1 in a free form is protic; and'}{'sub': '2', 'isolating an N, N′-sulfonyldiazole (Azole 1-SO-Azole 1).'}2. The method of claim 1 , wherein the first azole base structure is selected from the group consisting of imidazole claim 1 , pyrazole claim 1 , 1 claim 1 ,2 claim 1 ,4-triazole claim 1 , benzimidazole claim 1 , benzotriazole claim 1 , indazole claim 1 , 2-methylimidazole claim 1 , 2-methylbenzimidazole claim 1 , and 3 claim 1 ,5-dimethylpyrazole.3. The method of claim 1 , wherein the azolate salt is an azole anion salt having an ion of a metal selected from the group consisting of lithium claim 1 , sodium claim 1 , potassium claim 1 , cesium claim 1 , magnesium claim 1 , and a combination thereof.4. The method of claim 1 , wherein the azolate salt is derived from a protic azole and a metal carbonate claim 1 , the metal being selected from the group consisting of lithium claim 1 , sodium claim 1 , potassium claim 1 , cesium claim 1 , magnesium claim 1 , and a combination thereof.5. The method of claim 1 , wherein the azolate salt is derived from a protic azole and a metal fluoride claim 1 , the metal being ...

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Номер записи: 28
21-01-2016 дата публикации

SCREENING METHODS FOR THE BINDING AFFINITY OF CHEMICAL ENTITIES TO BIOLOGICAL MOLECULES AND NEDD4-1 INHIBITORS IDENTIFIED BY THE SCREENING METHODS

Номер: US20160016893A1
Автор: Kathman Stefan G., Statsyuk Alexander V.
Принадлежит: Northwestern University

Disclosed are methods for screening for the binding affinity of chemical entities to other bioactive molecules. The screened chemical entities may be utilized in pharmaceutical composition or therapeutic methods for treating disease or disorders associated with the bioactive molecules including NEDD4-1.

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Номер записи: 29
18-01-2018 дата публикации

SUBSTITUTED PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF

Номер: US20180016239A1
Автор: Barr Kenneth J., Fuller Peter H., Gunaydin Hakan, Lapointe Blair T., LIU Kun, Maclean John K. F., Molinari Danielle F., Sciammetta Nunzio, Simov Vladimir, Trotter Benjamin Wesley, Zhang Hongjun
Принадлежит:

The present invention relates to compounds according to Formula (I-1) and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions. 2. A compound of claim 1 , wherein Z is C(O).3. A compound of or claim 1 , wherein Ris independently OH or halogen.4. A compound of or claim 1 , wherein Ris independently OH claim 1 , chloro claim 1 , or fluoro.5. A compound of or claim 1 , wherein Ris OH.6. A compound of or claim 1 , wherein Ris fluoro.7. A compound of any one of - claim 1 , wherein m is 1.8. A compound of any one of - claim 1 , wherein Ris located meta to the —COH group.9. A compound of any one of - claim 1 , wherein Ris independently halogen claim 1 , (C)cycloalkyl claim 1 , or (C)cycloalkyl substituted by (C)haloalkyl.10. A compound of any one of - claim 1 , wherein Ris independently chloro claim 1 , cyclopropyl claim 1 , or cyclopropyl substituted by trifluoromethyl.11. A compound of any one of - claim 1 , wherein a first occurrence of Ris chloro claim 1 , and a second occurrence of Ris cyclopropyl.12. A compound of any one of - claim 1 , wherein a first occurrence of Ris chloro claim 1 , and a second occurrence of Ris cyclopropyl substituted by trifluoromethyl.14. A compound of any one of - claim 1 , wherein any Ris located at an ortho-position on the phenyl group to which Ris attached.15. A compound of any one of - claim 1 , wherein n is 2.18. A compound of any one of - claim 1 , wherein Ris independently (C)alkyl claim 1 , 2-8 membered heteroalkyl claim 1 , or -(3-10 membered heterocyclyl optionally substituted by one or more R).20. A compound of any one of - claim 1 , wherein Ris a 3-10 membered heterocyclyl optionally substituted by one or more R.21. A compound of any one of - claim 1 , wherein Ris a 3-10 membered spirocyclic heterocyclyl optionally substituted by one or more R.22. A compound of any one of - claim 1 , wherein Ris independently halogen claim 1 , hydroxyl claim 1 , or (C) ...

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Номер записи: 30
17-01-2019 дата публикации

MAST-CELL MODULATORS AND USES THEREOF

Номер: US20190016680A1
Автор: Sun Lijun, Veves Aristidis
Принадлежит:

Provided are novel compounds of Formula I pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders associated with mast cells. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more diseases and disorders associated with mast cells. 4. The compound of claim 1 , wherein p is 2.5. The compound of claim 1 , wherein s is 1 or 2.6. The compound of claim 1 , wherein Ris fluoro.7. The compound of claim 1 , wherein Ris chloro.9. A pharmaceutical composition comprising the compound of any claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , polymorph claim 1 , or solvate thereof; and a pharmaceutically acceptable carrier.15. The method of claim 10 , wherein claim 10 , Cy is phenyl or pyridyl.16. The method of claim 10 , wherein Rand Rare each halo.17. The method of claim 10 , wherein p and s are each independently 1 claim 10 , 2 claim 10 , or 3.18. The method of claim 10 , wherein p is 2.19. The method of claim 10 , wherein s is 1 or 2.20. The method of claim 10 , wherein Ris fluoro.21. The method of claim 10 , wherein Ris chloro. This application claims priority to U.S. Provisional Application No. 62/278,722, filed Jan. 14, 2016, the entire contents of which are incorporated herein by reference.The present disclosure relates to mast cell (MC) modulators, processes for their preparation, pharmaceutical compositions containing these modulators, and their use in the treatment of diseases associated with mast cells.Traditionally, mast cells have been known for their role in allergic and anaphylactic reactions, as well as their involvement in acquired and innate immunity, bacterial infections, and autoimmunity. See e.g., Respitory Medicine, Volume 106, Issue 1, pp. 9-14 (January 2012); Proc. Natl Acad. Sci. USA 102 (2005) 1578-1583; Nat. Immunol. 6 (2005) 135-142; Nature 432 (2004) 512-516; Eur. J ...

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Номер записи: 31
28-01-2016 дата публикации

ARGININE METHYLTRANSFERASE INHIBITORS AND USES THEREOF

Номер: US20160024017A1
Автор: Chesworth Richard, Kuntz Kevin Wayne, MITCHELL Lorna Helen, Shapiro Gideon
Принадлежит: EPIZYME, INC.

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described. 5. The compound of claim 3 , wherein Ris branched Calkyl.2625. The compound of any one of - claims 1 , wherein X is NRand Y is N.2725. The compound of any one of - claims 1 , wherein X is N and Y is NR.2928. A pharmaceutical composition comprising a compound of any one of - claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , and optionally a pharmaceutically acceptable excipient.30. The pharmaceutical composition of claim 29 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound.3128. A kit or packaged pharmaceutical comprising a compound of any one of - or a pharmaceutically acceptable salt thereof claims 1 , and instructions for use thereof.3228. A method of inhibiting an arginine methyl tranferase (RMT) comprising contacting a cell with an effective amount of a compound of any one of - or a pharmaceutically acceptable salt thereof.33. The method of claim 32 , wherein the arginine methyl transferase is PRMT1.34. The method of claim 32 , wherein the arginine methyl transferase is PRMT3.35. The method of claim 32 , wherein the arginine methyl transferase is PRMT4.36. The method of claim 32 , wherein the arginine methyl transferase is PRMT6.37. The method of claim 32 , wherein the arginine methyl transferase is PRMT8.3828. A method of modulating gene expression comprising contacting a cell with an effective amount of a compound of any one of - or a pharmaceutically acceptable salt thereof.3928. A method of modulating transcription comprising contacting a cell with an effective amount of a compound of any one of - or a pharmaceutically acceptable salt thereof.4039. The ...

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Номер записи: 32
28-01-2016 дата публикации

Substituted 6,5-Fused Bicyclic Heteroaryl Compounds

Номер: US20160024081A1
Автор: CAMPBELL John Emmerson, Kuntz Kevin Wayne
Принадлежит:

The present invention relates to azole bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes. 4. The compound of claim 3 , Ris tetrahydropyranyl claim 3 , piperidine substituted by 1 claim 3 , 2 claim 3 , or 3 Calkyl groups claim 3 , or cyclohexyl substituted by N(Calkyl)wherein one or both of the Calkyl is optionally substituted with Calkoxyl.5. The compound of claim 1 , wherein Ris sec-butyl claim 1 , cyclopentyl claim 1 , or iso-propyl.14. The compound of claim 1 , wherein X is imidazol-2-yl claim 1 , imidazol-4-yl claim 1 , triazol-3-yl claim 1 , 3H-imidazo[4 claim 1 ,5-c]pyridin-7-yl claim 1 , 1H-benzo[d]imidazol-4-yl claim 1 , 1H-indazol-7-yl claim 1 , isoxazol-3-yl claim 1 , thiazol-2-yl claim 1 , 1H-pyrazolo[4 claim 1 ,3-c]pyridin-7-yl claim 1 , imidazo[1 claim 1 ,2-a]pyridin-8-yl claim 1 , imidazo[1 claim 1 ,2-c]pyrimidin-8-yl claim 1 , 1 claim 1 ,4 claim 1 ,6 claim 1 ,7-tetrahydropyrano[4 claim 1 ,3-c]pyrazol-7-yl claim 1 , 1 claim 1 ,4 claim 1 ,6 claim 1 ,7-tetrahydropyrano[3 claim 1 ,4-]imidazol-7-yl claim 1 , 4 claim 1 ,5 claim 1 ,6 claim 1 ,7-tetrahydro-1H-benzo[d]imidazol-4-yl claim 1 , 7H-pyrrolo[2 claim 1 ,3-d]pyrimidine-4-yl claim 1 , 9H-purine-6-yl claim 1 , 7-methyl-[1 claim 1 ,2 claim 1 ,4]triazolo[4 claim 1 ,3-a]pyridin-5-ol-6-yl claim 1 , [1 claim 1 ,2 claim 1 ,4]triazolo[4 claim 1 ,3-a]pyridin-6-yl claim 1 , 3-fluoro-1 claim 1 ,5-dimethyl-1H-pyrazol-4-yl claim 1 , or 5-fluoro-1 claim 1 ,3-dimethyl-1H-pyrazol-4-yl.15. The compound of claim 1 , wherein the compound is selected from those in Tables 1-3 and pharmaceutically acceptable salts thereof.16. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt ...

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Номер записи: 33
17-04-2014 дата публикации

BCL-2-SELECTIVE APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE DISEASES

Номер: US20140107119A1
Автор: Bruncko Milan, Ding Hong, Doherty George A., Elmore Steven W., Hansen Todd M., Hasvold Lisa, Hexamer Laura A., Kunzer Aaron R., Mantei Robert A., McClellan William J., Park Chang H., Park Cheol-Min, PETROS ANDREW M., Song Xiaohong, Souers Andrew J., Sullivan Gerard M., Tao Zhi-Fu, Wang Gary T., Wang Le, Wang Xilu, Wendt Michael D.
Принадлежит: AbbVie Inc.

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein. 6. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A); and'}{'sup': '2', 'Ais H.'}7. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H; and'}{'sup': 1', '1, 'Bis NHR.'}8. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H;'}{'sup': 1', '1, 'Bis NHR; and'}D1 is H.9. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H;'}{'sup': 1', '1, 'Bis NHR;'}{'sup': '1', 'Dis H; and'}{'sup': '1', 'Eis H.'}10. The compound of , , , , or , wherein{'sup': 1', '2, 'Ais C(A) or N;'}{'sup': '2', 'Ais H;'}{'sup': 1', '1, 'Bis NHR;'}{'sup': '1', 'Dis H;'}{'sup': '1', 'Eis H; and'}{'sup': '1', 'sub': '2', 'Yis NO.'}11. A compound of claim 1 , wherein the compound is chosen from:4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-phenoxybenzamide;benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-2-phenoxy-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;2-(benzyloxy)-4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(2-phenylethoxy)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(phenylthio)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-2-(phenylthio)-N-((4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)benzamide;4-(4-((4′-chloro-1,1′-biphenyl-2-yl)methyl)piperazin-1-yl)-N-((4-((3-morpholin-4- ...

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Номер записи: 34
25-01-2018 дата публикации

ARYL SUBSTITUTED INDOLES AND THE USE THEREOF

Номер: US20180022699A1
Автор: Kyle Donald J., Ni Chiyou, TAFESSE Laykea, Yao Jiangchao
Принадлежит:

The invention relates to aryl and heteroaryl substituted compounds of Formula (I), and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein G, R, and Z-Zare defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain. 160-. (canceled)62. (canceled)6474-. (canceled)75. A pharmaceutical composition claim 61 , comprising the compound of claim 61 , or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , and a pharmaceutically acceptable carrier.7679-. (canceled)80. A method for treating pain in a mammal claim 61 , comprising administering an effective amount of a compound as claimed in or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , to a mammal in need of such treatment.81. (canceled)82. The method of claim 80 , wherein the method is for preemptive or palliative treatment of pain.83. The method of claim 80 , wherein said pain is selected from the group consisting of chronic pain claim 80 , inflammatory pain claim 80 , neuropathic pain claim 80 , postsurgical pain claim 80 , acute pain claim 80 , and surgical pain.84. A method of modulating sodium channels in a mammal claim 61 , comprising administering to the mammal at least one compound as claimed in or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , wherein Na1.7 sodium channel is modulated.85. (canceled)86. A compound as claimed in claim 61 , wherein the compound is H claim 61 , C claim 61 , or C radiolabeled claim 61 , or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof.8791-. (canceled)92. A pharmaceutical composition claim 63 , comprising the compound of claim 63 , or a pharmaceutically acceptable salt claim 63 , prodrug or solvate thereof claim 63 , and a pharmaceutically ...

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Номер записи: 35
10-02-2022 дата публикации

BENZO-AND PYRIDO-PYRAZOLES AS PROTEIN KINASE INHIBITORS

Номер: US20220041559A1
Автор: Artusi Roberto, Bovino Clara, BUZZI Benedetta, Colace Fabrizio, Mandelli Stefano, PIEPOLI Tiziana, Rovati Lucio Claudio
Принадлежит:

The invention relates to new chemical compounds of Formula (I), pharmaceutical compositions containing them, and their use for the pharmacological treatment of a cancer, preferably a glioblastoma. 2. The compound of wherein Ris H or 3-oxethanylmethylenoxy.3. The compound of wherein X is C.4. The compound of wherein X is N.5. The compound of wherein Y is C.6. The compound of claim 1 , wherein Ris the substituent (a) claim 1 , wherein Z is carbon claim 1 , or the substituent (b) claim 1 , preferably Ris the substituent (a) wherein Z is carbon.7. The compound of claim 1 , wherein Ris piperidinyl claim 1 , piperazinyl or 4-piperidinyloxy claim 1 , preferably piperidinyl.8. The compound of claim 1 , selected from the group consisting of:N-(6-((2-chloro-6-fluorophenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;N-(6-((2-ethyl-6-fluorophenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;4-((3 S,4R)-3-fluoro-1-methylpiperidin-4-yl)-N-(6-((2-fluorophenyl)amino)-1H-indazol-3-yl)benzamide;4-((3R,4S)-3-fluoro-1-methylpiperidin-4-yl)-N-(6-((2-fluorophenyl)amino)-1H-indazol-3-yl)benzamide;N-(6-((2-fluorophenyl)amino)-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;N-(6-((4-cyano-2-fluorophenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;N-(6-((2-fluorophenyl)amino)-1H-indazol-3-yl)-4-(1-(oxetan-3-yl)piperidin-4-yl)benzamide;N-(6-((2-fluoro-4-methylphenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;N-(6-((2-chloro-4-fluorophenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;4-(1-methylpiperidin-4-yl)-N-(6-((2-(trifluoromethyl)phenyl)amino)-1H-indazol-3-yl)benzamide;N-(6-((2-fluoro-6-methylphenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;N-(6-((4-chloro-2-fluorophenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl)benzamide;N-(6-((2-chloro-6-methylphenyl)amino)-1H-indazol-3-yl)-4-(1-methylpiperidin-4-yl) benzamide;N-(6-((2-chlorophenyl)amino)-1H-indazol-3-yl)-4-(1- ...

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Номер записи: 36
23-01-2020 дата публикации

FUSED DIHYDRO-4H-PYRAZOLO[5,1-C][1,4]OXAZINYL COMPOUNDS AND ANALOGS FOR TREATING CNS DISORDERS

Номер: US20200024286A1
Автор: Alexandrov Vadim, Chytil Milan, Engel Sharon, HANANIA Taleen G., Leahy Emer
Принадлежит:

Disclosed are compounds of Formula (I): 155-. (canceled)57. A process according to claim 56 , wherein said resolving is accomplished by chiral HPLC.62. A process according to claim 61 , wherein said resolving in step e) is accomplished by chiral HPLC. This application is a continuation application of U.S. patent application Ser. No. 15/041,827, filed Feb. 11, 2016, now allowed, which claims the benefit of U.S. Provisional Application No. 62/115,043, filed Feb. 11, 2015. The disclosures of each of these prior applications are hereby incorporated herein by reference in their entirety.Central nervous system disorders affect a wide range of the population with differing severity. Neurological and psychiatric disorders include major depression, schizophrenia, bipolar disorder, obsessive compulsive disorder (OCD), panic disorder, and posttraumatic stress disorder (PTSD), among others. These disorders affect a person's thoughts, mood, behavior and social interactions and can significantly impair daily functioning. See, e.g., 4Ed., American Psychiatric Association (2000) (“DSM-IV-TR”); 5Ed., American Psychiatric Association (2013) (“DSM-5”).Bipolar disorder is a serious psychiatric disorder that has a prevalence of approximately 2% of the population, and affects both genders alike. It is a relapsing-remitting condition characterized by cycling between elevated (i.e., manic) and depressed moods, which distinguishes it from other disorders such as major depressive disorder and schizophrenia. Bipolar I is defined by the occurrence of a full manic episode, although most individuals experience significant depression. Symptoms of mania include elevated or irritable mood, hyperactivity, grandiosity, decreased need for sleep, racing thoughts and in some cases, psychosis. The depressive episodes are characterized by anhedonia, sad mood, hopelessness, poor self-esteem, diminished concentration and lethargy. Bipolar II is defined as the occurrence of a major depressive episode and ...

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Номер записи: 37
28-01-2021 дата публикации

BICYCLIC CARBOXAMIDES AND METHODS OF USE THEREOF

Номер: US20210024491A1
Автор: BRAVO Yalda, Chen Austin Chih-Yu, DING Jinyue, GOMEZ Robert, LAM Heather, NAGAMIZO Joe Fred, OBALLA Renata Marcella, POWELL David Andrew, SHENG Tao
Принадлежит:

Compounds, compositions and methods are provided for modulating the activity of EPand EPreceptors, and for the treatment, prevention and amelioration of one or more symptoms of diseases or disorders related to the activity of EPand EPreceptors. In certain embodiments, the compounds are antagonists of both the EPand EPreceptors. 2. The compound of wherein:{'sup': 1', 'b, 'sub': 2', 't, 'Lis —(CR)—;'}Ring A is optionally deuterated aryl;{'sup': 1', '8′', 'y, 'sub': 2', '9', '2', '9', '2', '9', '2', '9', '2', '9', '2', '9, 'each Ris independently C-Calkyl, C-Calkenyl, C-Calkynyll, cycloalkyl, heterocyclyl, aryl, heteroaryl or —OR, wherein C-Calkyl, C-Calkenyl, C-Calkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally deuterated and optionally substituted with one, two, or three R;'}{'sup': 1', '10', 'y, 'sub': '2', 'or two Rsubstituents on adjacent atoms of Ring A are taken together with the atom to which they are attached to form an aromatic or non-aromatic ring containing 0-2 heteroatoms selected from the group consisting of —O—, ═N—, —NR—,—S—, and —S(O)—, wherein the aromatic or non-aromatic ting is optionally deuterated and optionally substituted with one, two, or three R;'}{'sup': 2', '3', '4', '5', '8', '8', '9', '8', '11', '11, 'sub': '2', 'R, R, R, and Rare each independently hydrogen, alkyl, halogen, —OR, —NRR, —SR, —S(O)R, —S(O)R, —CN, cycloalkyl, or haloalkyl;'}{'sup': '7', 'Ris hydrogen, deuterium, halogen, optionally deuterated alkyl, alkoxy, haloallkoxy, hydroxyl, or haloalkyl;'}{'sup': 8', '9, 'each Rand each Rare independently hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one, two, or three groups selected from halogen, alkyl, and haloalkyl; or'}{'sup': 8', '9, 'Rand R, together with the atom or atoms to which they are attached, form a heterocyclyl optionally substituted with one, two, or three ...

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Номер записи: 38
29-01-2015 дата публикации

CRYSTALLINE FORMS OF 1-(3-TERT-BUTYL-1-P-TOLYL-1H-PYRAZOL-5-YL)-3-(5-FLUORO-2-(1-(2-HYDROXYETHYL)-INDAZOL-5-YLOXY)BENZYL)UREA HYDROCHLORIDE

Номер: US20150030673A1
Автор: Arrigo Alisha B., Corson Donald T., Mannila Coralee G.
Принадлежит: ARRAY BIOPHARMA INC.

Provided herein is a hydrogen chloride salt of 1-(3-/t?r/-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzyl)urea, crystalline forms of 1-(3-½̂butyl-1̂-tolyl-1H-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzyl)urea hydrochloride, processes for the preparation of said crystalline forms, pharmaceutical compositions containing a crystalline form of 1-(3-r Подробнее

Номер записи: 39
02-02-2017 дата публикации

Selective androgen receptor degrader (sard) ligands and methods of use thereof

Номер: US20170029370A1
Автор: Charles B. Duke, Christopher C. Coss, Dong-Jin Hwang, Duane D. Miller, James T. Dalton, Jayaprakash Pagadala, Ramesh Narayanan, Thamarai Ponnusamy, Yali He
Принадлежит: GTx Inc, UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION

This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, other AR-expressing cancers, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels (through degradation) and/or activity (through inhibition) of any androgen receptor including androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

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Номер записи: 40
02-02-2017 дата публикации

ANTIBACTERIAL 1H-INDAZOLE AND 1H-INDOLE DERIVATIVES

Номер: US20170029411A1
Автор: CHAPOUX Gaelle, GAUVIN Jean-Christophe, Hubschwerlen Christian, MIRRE Azely, OCHALA Etienne, SPECKLIN Jean-Luc, SURIVET Jean-Philippe
Принадлежит: ACTELION PHARMACEUTICALS LTD

The invention relates to antibacterial compounds of formula I 4. The compound of formula I according to claim 1 , wherein Rrepresents H or fluorine claim 1 , Rrepresents H or fluorine claim 1 , Rrepresents H or fluorine and Rrepresents H;or a salt thereof.5. The compound of formula I according to claim 1 , wherein Rrepresents the group M;or a salt thereof.6. The compound of formula I according to claim 5 , wherein A represents a bond;or a salt thereof.7. The compound of formula I according to claim 5 , wherein A represents C≡C;or a salt thereof.8. The compound of formula I according to claim 7 , wherein Rrepresents H or fluorine claim 7 , Rrepresents H and Rrepresents hydroxy(C-C)alkyl claim 7 , trans-2-hydroxymethyl-cycloprop-1-yl claim 7 , 1 claim 7 ,2-dihydroxyethyl claim 7 , 3-hydroxyoxetan-3-yl or 3-hydroxythietan-3-yl;or a salt thereof.9. The compound of formula I according to claim 7 , wherein Rrepresents the group M;or a salt thereof.10. The compound of formula I according to claim 9 , wherein Rrepresents 3-hydroxyoxetan-3-yl claim 9 , 2-aminoprop-2-yl claim 9 , 1-hydroxymethyl-cycloprop-1-yl or trans-2-hydroxymethyl-cycloprop-1-yl;or a salt thereof.11. The compound of formula I according to claim 1 , wherein the compound is:(R)-4-(5-(but-2-yn-1-yloxy)-1H-indol-1-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(R)-4-(5-(2-fluoro-3-methoxyphenyl)-1H-indazol-1-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(R)-(E)-N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(5-styryl-1H-indazol-1-yl)butanamide;(R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(5-phenethyl-1H-indazol-1-yl)butanamide;(R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(5-((4-(morpholinomethyl)phenyl)ethynyl)-1H-indazol-1-yl)butanamide 4-toluenesulfonic acid salt;(R)-4-(5-((4-aminophenyl)ethynyl)-1H-indazol-1-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(5-(4-(trifluoromethoxy)phenyl)-1H-indazol-1-yl)butanamide;(R)-4-(5-(4-(2H-1,2,3-triazol-2-yl)phenyl)- ...

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Номер записи: 41
04-02-2016 дата публикации

HDAC INHIBITORS

Номер: US20160031823A1
Автор: Jacques Vincent, Rusche James R.
Принадлежит:

Disclosed herein are compounds of formula (I), and methods of inhibiting histone deacetylase (“HDAC”) enzymes (e.g., HDAC1, HDAC2, and HDAC3) using compounds of formula (I). 43. The compound or salt of any one of - claims 1 , wherein X is —Y—[C(R)]-A-[C(R)]—B—.5. The compound or salt of claim 4 , wherein A is a bond claim 4 , B is a bond claim 4 , or both A and B are each a bond.6. The compound or salt of or claim 4 , wherein each occurrence of Rand Ris independently selected from H claim 4 , F claim 4 , OH claim 4 , C1-C6 alkyl claim 4 , C3-C6 cycloalkyl claim 4 , NH claim 4 , OCO—(C1-C6 alkyl) claim 4 , OCO—(C3-C6 cycloalkyl) claim 4 , C1-C6 alkoxy claim 4 , C1-C6 fluoroalkoxy claim 4 , and cyano.76. The compound or salt according to any one of - claims 4 , wherein each occurrence of Rand Ris independently selected from H claims 4 , F claims 4 , C1-C6 alkyl claims 4 , and C3-C6 cycloalkyl.87. The compound or salt according to any one of - claims 4 , wherein each occurrence of Rand Ris H.9. The compound or salt of claim 4 , wherein Y is a bond.10. The compound or salt according to claim 9 , wherein A is a bond claim 9 , O claim 9 , or NR.11. The compound or salt according to or claim 9 , wherein A is a bond.1211. The compound or salt according to any one of - claims 9 , wherein each occurrence of Rand Ris independently selected from H claims 9 , F claims 9 , OH claims 9 , C1-C6 alkyl claims 9 , C3-C6 cycloalkyl claims 9 , NH claims 9 , OCO—(C1-C6 alkyl) claims 9 , OCO—(C3-C6 cycloalkyl) claims 9 , C1-C6 alkoxy claims 9 , C1-C6 fluoroalkoxy claims 9 , and cyano.1312. The compound or salt according to any one of - claims 9 , wherein each occurrence of Rand Ris independently selected from H claims 9 , F claims 9 , C1-C6 alkyl claims 9 , and C3-C6 cycloalkyl.1413. The compound or salt according to any one of any one of - claims 9 , wherein each occurrence of Rand Ris H.1514. The compound or salt according to any one of - claims 9 , wherein a is 1.1615. The compound or ...

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Номер записи: 42
04-02-2016 дата публикации

Substituted Benzene Compounds

Номер: US20160031907A1
Автор: CAMPBELL John Emmerson, Kuntz Kevin Wayne
Принадлежит:

The present invention relates to compounds of Formula (I), wherein the variables are as defined herein. Pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof are disclosed. 3. The compound of claim 2 , wherein Dis N; each of Dand D claim 2 , independently claim 2 , is CR; and Dis NR.4. The compound of claim 2 , wherein each of Dand D claim 2 , independently claim 2 , is CR; Dis N; and Dis NR.5. The compound of claim 2 , wherein each of Dand Dis N; Dis CR; and Dis NR.6. The compound of claim 2 , wherein each of Dand Dis claim 2 , independently claim 2 , CR; Dis N claim 2 , and Dis NR.7. The compound of claim 2 , wherein Dis N; each of Dand D claim 2 , independently claim 2 , is CR; and Dis O or S.9. The compound of claim 8 , wherein Eis N; each of Eand E claim 8 , independently claim 8 , is CR; and Eis NR.10. The compound of claim 8 , wherein each of Eand E claim 8 , independently claim 8 , is CR; Eis N; and Eis NR.11. The compound of claim 8 , wherein each of Eand E claim 8 , independently claim 8 , is CR; Eis NR; and Eis N.12. The compound of claim 8 , wherein each of Eand E claim 8 , independently claim 8 , is CR; Eis O; and Eis N.14. The compound of claim 13 , wherein Gis NR; Gis CR; and each of Gand G claim 13 , if present claim 13 , is N.15. The compound of claim 13 , wherein Gis NR; each of Gand G claim 13 , if present claim 13 , independently claim 13 , is CR; and Gis N.16. The compound of claim 13 , wherein Gis NR; each of Gand G claim 13 , if present claim 13 , is N claim 13 , and Gis CR.17. The compound of claim 13 , wherein Gis NR; Gis N; and each of Gand G claim 13 , if present claim 13 , independently claim 13 , is CR.19. The compound of claim 18 , wherein J claim 18 , if present claim 18 , is N claim 18 , and each of J claim 18 , J claim 18 , and J claim 18 , independently claim 18 , is CR.22. The compound of claim 21 , wherein ...

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Номер записи: 43
30-01-2020 дата публикации

Pesticial Compounds

Номер: US20200029566A1
Автор: Adisechan Ashokkumar, CHAUDHURI Rupsha, Datta Gopal Krishna, Narine Arun, SAMBASIVAN Sunderraman, VALLINAYAGAM Ramakrishnan, VYAS Devendra
Принадлежит:

The present invention relates to the compounds of formula (I), and the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof wherein the variables are defined according to the description, 115-. (canceled)17: The compound of claim 16 , wherein W is O claim 16 , Ais CR claim 16 , Ais CR claim 16 , and Ais N.18: The compound of claim 16 , wherein W is N claim 16 , Ais CR claim 16 , Ais CR claim 16 , and Ais N.19: The compound of claim 16 , wherein W is O claim 16 , Ais CR claim 16 , Ais CR claim 16 , and Ais CR.20: The compound of claim 16 , wherein W is N claim 16 , Ais CR claim 16 , Ais CR claim 16 , and Ais CR.21: The compound of claim 16 , wherein W is N claim 16 , Ais N claim 16 , Ais N claim 16 , and Ais CR.22: The compound of claim 16 , wherein W is S(═O) claim 16 , Ais CR claim 16 , Ais CR claim 16 , and Ais CR.25: A composition claim 16 , comprising a compound of claim 16 , an N-oxide or an agriculturally acceptable salt thereof claim 16 , and a further active substance.26: A method for combating or controlling invertebrate pests claim 16 , which method comprises contacting said pest or its food supply claim 16 , habitat or breeding grounds with a pesticidally effective amount of at least a compound of .27: A method for protecting growing plants from attack or infestation by invertebrate pests claim 16 , which method comprises contacting a plant claim 16 , or soil or water wherein the plant is growing claim 16 , with a pesticidally effective amount of at least a compound of .28: Seed treated with a compound of claim 16 , or the enantiomers claim 16 , diastereomers or salts thereof claim 16 , in an amount of from 0.1 g to 10 kg per 100 kg of seed.29: A method for treating or protecting an animal from infestation or infection by invertebrate pests which comprises bringing the animal in contact with a pesticidally effective amount of at least one compound of claim 16 , a stereoisomer thereof and/or at least one ...

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Номер записи: 44
30-01-2020 дата публикации

INDAZOLE AND INDOLE DERIVATIVES AS INHIBITORS OF RETINOIC ACID RELATED ORPHAN RECEPTOR GAMMA (ROR GAMMA) FOR THE TREATMENT OF IMMUNE-RELATED DISEASES

Номер: US20200030290A1
Автор: McCARTHY Clive, OLSSON Roine Inge, Went Naomi
Принадлежит:

The present invention provides compounds of formula (I), wherein A, A, Z, Z, Z, R, R, R, R, R, R, n, p and q are as defined herein. In certain embodiments, the compounds of the invention are RORγt antagonists. In other embodiments, the compounds of the invention are useful in the treatment and/or prevention of inflammatory and autoimmune conditions. 23-. (canceled)4. The compound of claim 1 , wherein in the Aring the group C(═O)ORis positioned at the meta or para position of the ring relative to the remainder of the molecule.5. The compound of wherein:{'sup': 1', '1, 'Ais phenyl and the group C(═O)ORis at the 4-position of the ring; or'}{'sup': 1', '1, 'Ais 2-pyridyl and the C(═O)ORgroup is at the 5-position of the pyridyl ring; or'}{'sup': 1', '1, 'Ais 3-pyridyl and the C(═O)ORgroup is at the 6-position of the pyridyl ring.'}6. The compound of claim 1 , wherein Ais phenyl or 4-pyridyl.8. The compound of claim 1 , wherein Ris H claim 1 , Calkyl or benzyl.9. The compound of claim 1 , wherein n is 0 claim 1 , 1 claim 1 , or 2 and R claim 1 , when present is chloro claim 1 , fluoro claim 1 , methyl claim 1 , or trifluoromethyl; or wherein n is 0 claim 1 , 1 claim 1 , or 2 and R claim 1 , when present claim 1 , is OH.10. The compound of claim 1 , wherein n is 0 or 1.11. The compound of claim 1 , wherein each Ris independently selected from the group consisting of halo claim 1 , CN claim 1 , NO claim 1 , OH claim 1 , NRRand Calkyl optionally substituted with one or more substituents selected from the group consisting of phenyl claim 1 , halo claim 1 , CN claim 1 , NO claim 1 , OH claim 1 , and NRR;{'sup': 12', '13, 'sub': 1-2', '3-7, 'wherein each Rand Ris independently selected from the group consisting of hydrogen, Calkyl optionally substituted with one or more halo substituents, and Ccycloalkyl optionally substituted with one or more halo substituents.'}12. The compound of claim 1 , wherein p is 2 claim 1 , one of the Rgroups is halo and the other is trifluoromethyl. ...

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Номер записи: 45
30-01-2020 дата публикации

AGENT FOR REDUCING VISCERAL FAT WEIGHT

Номер: US20200030299A1
Автор: Murakami Kentaro, Takizawa Toshiaki
Принадлежит: KOWA CO., LTD.

An FGF21 production promoting agent containing, as an active ingredient, a compound represented by the following formula (1): 1. A method for reducing visceral fat weight comprising administering, to a subject in need thereof, a compound represented by the following formula (1):{'sup': 1', '2', '3a', '3b', '4a', '4b', '3a', '3b', '4a', '4b', '5', '5, 'sub': 1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', 'l, 'wherein each of Rand R, which may be identical to or different from each other, represents a hydrogen atom, a methyl group, or an ethyl group; each of R, R, R, and R, which may be identical to or different from one another, represents a hydrogen atom, a halogen atom, a nitro group, a hydroxyl group, a Calkyl group, a trifluoromethyl group, a Calkoxy group, a Calkylcarbonyloxy group, a di-Calkylamino group, a Calkylsulfonyloxy group, a Calkylsulfonyl group, a Calkylsulfinyl group, or a Calkylthio group, or Rand Ror Rand Rmay bond together to form an alkylenedioxy group; X represents an oxygen atom, a sulfur atom, or N—R(Rrepresents a hydrogen atom, a Calkyl group, a Calkylsulfonyl group, or a Calkyloxycarbonyl group); Y represents an oxygen atom, an S(O)group (l is a number of from 0 to 2), a carbonyl group, a carbonylamino group, an aminocarbonyl group, a sulfonylamino group, an aminosulfonyl group, or an NH group;'}Z represents CH or N; n is a number of from 1 to 6; and m is a number of from 2 to 6, a salt of the compound, or a solvate of the compound or the salt. This application is a continuation of U.S. application Ser. No. 15/787,049, filed on Oct. 18, 2017, which is a continuation of U.S. application Ser. No. 15/145,090, filed on May 3, 2016, which is a continuation of U.S. application Ser. No. 13/393,164, filed on Feb. 28, 2012, and incorporated herein by reference, which is a National Stage of PCT/JP10/066678 filed Sep. 27, 2010 and claims the benefit of JP 2009-222853 filed on Sep. 28, 2009.The present invention relates to ...

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Номер записи: 46
04-02-2021 дата публикации

COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR MODULATING SGK ACTIVITY, AND METHODS THEREOF

Номер: US20210032239A1
Автор: Xian Jun
Принадлежит:

The invention provides novel chemical compounds useful for treating one or more of autoimmune diseases, cancer, cardiovascular diseases, inflammatory diseases and diabetes, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof. 4. The compound of claim 1 , wherein Y claim 1 , Yand Yare selected from the group consisting of:{'sub': 1', '1', '2', '2', '3', '3, 'Y=CR, Y=CR, Y=CR;'}{'sub': 1', '1', '2', '3', '3, 'Y=CR, Y=N, Y=CR;'}{'sub': 1', '1', '2', '2', '3, 'Y=CR, Y=CR, Y=N;'}{'sub': 1', '2', '3', '3, 'Y=N, Y=N, Y=CR; and'}{'sub': 1', '2', '2', '3, 'Y=N, Y=CR, Y=N.'}5. (canceled)7. The compound of claim 1 , wherein Zand Zare selected from the group consisting of:{'sub': 1', '2, 'Z=Z=CR;'}{'sub': 1', '2, 'Z=Z=N;'}{'sub': 1', '2, 'Z=N, Z=CR; and'}{'sub': 1', '2, 'Z=CR, Z=N,'}wherein each R is H.8. (canceled)11. The compound of claim 9 , wherein X is F or Cl claim 9 , R=R=R=H claim 9 , Ris NH claim 9 , Ris OR claim 9 , wherein Ris a hydrogen or a C-Calkyl group.12. The compound of claim 9 , wherein at least one of Zand Zis N.13. The compound of claim 9 , wherein at least one of Yand Yis not N.15. The compound of claim 14 , wherein X is F claim 14 , Ris CH claim 14 , Yis CH claim 14 , Yis N claim 14 , and Ris a C-Calkyl group.16. (canceled)17. The compound of claim 14 , wherein X is F claim 14 , Ris CH claim 14 , Yis N claim 14 , Yis CH claim 14 , and Ris a C-Calkyl group.18. (canceled)19. The compound of claim 14 , wherein X is F claim 14 , Ris CH claim 14 , Yis CH claim 14 , Yis CH claim 14 , and Ris a C-Calkyl group.20. (canceled)22. (canceled)23. (canceled)2530-. (canceled)31. A unit dosage form comprising a pharmaceutical composition according to .3338-. (canceled)39. The method of claim 32 , wherein the compound effectively inhibits serum and glucocorticoid-regulated kinase (SGK) 1 and/or 2. This application claims the benefit of U.S. Provisional Application No. 62/431,203, filed Dec. 7, 2016, the ...

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Номер записи: 47
04-02-2021 дата публикации

Indene derivatives useful in treating pain and inflammation

Номер: US20210032264A1
Автор: Curtis Harwig, Jennifer CROSS, Jeremy D. PETTIGREW, Jeyaprakashnarayanan Seenisamy, Karthikeyan IYANAR, Mahesh Narayan Keregadde
Принадлежит: Aquinox Pharmaceuticals Canada Inc

Compounds of formula (I): wherein, R 1 , R 2 , R 3 , R 4a , R 4b and R 5 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds are useful in treating inflammation and/or pain. Compositions comprising a compound of the invention are also disclosed, as are methods of using the compounds to treat inflammation and/or pain.

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Номер записи: 48
11-02-2016 дата публикации

CRYSTALLINE FORMS OF AN ESTROGEN RECEPTOR MODULATOR

Номер: US20160039770A1
Автор: Herbert Mark R., Smith Nicholas D.
Принадлежит: Genentech, Inc.

Described herein are amorphous and crystalline forms of pharmaceutically acceptable salts of the estrogen receptor modulator (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid. Also described are pharmaceutical compositions suitable for administration to a mammal that include the estrogen receptor modulator, and methods of using the estrogen receptor modulator, alone and in combination with other compounds, for treating diseases or conditions that are associated with estrogen receptor activity. 1. A pharmaceutically acceptable salt of (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid , wherein the pharmaceutically acceptable salt is in crystalline form.2. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is a potassium salt claim 1 , magnesium claim 1 , a L-arginine salt claim 1 , choline salt claim 1 , ethylenediamine salt claim 1 , N-methyl glucamine salt claim 1 , tromethamine salt claim 1 , or hydroxyethylpyrrolidine salt.3. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is a N-methyl glucamine salt.4. A crystalline Form 1 of (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid claim 1 , N-methyl glucamine salt that is characterized as having:{'figref': {'@idref': 'DRAWINGS', 'FIG. 1'}, '(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in ;'}(b) an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 4.7±0.1° 2-Theta, 9.4±0.1° 2-Theta, 12.3±0.1° 2-Theta, 14.1±0.1° 2-Theta, 17.3±0.1° 2-Theta, 18.7±0.1° 2-Theta, 19.9±0.1° 2-Theta, 20.2±0.1° 2-Theta, 21.5±0.1° 2-Theta, 24.3±0.1° 2-Theta, 24.7±0.1° 2-Theta;(c) substantially the same X-ray powder diffraction (XRPD) pattern post storage at 40° C. and 75% RH for at least a week;(d) substantially the same X-ray powder diffraction (XRPD) pattern post ...

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Номер записи: 49
11-02-2016 дата публикации

Deoxyuridine triphosphatase inhibitors

Номер: US20160039788A1
Автор: Bruno Giethlen, Robert D. Ladner
Принадлежит: University of Southern California USC

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

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Номер записи: 50
24-02-2022 дата публикации

PREPARATION AND APPLICATION OF CLASS OF N-CONTAINING HETEROCYCLIC COMPOUNDS HAVING IMMUNOREGULATORY FUNCTION

Номер: US20220056023A1
Автор: DENG Jianwen, Feng Zhiyong, JIANG Lei, LU Xiaoli, Shang Ke, SHOU Jianyong, WANG Bing, XU Xueli, Xu Yuan, Zhang Yi
Принадлежит:

The present invention discloses the preparation and application of heterocyclic compound having immunoregulatory function. Specifically, the present invention discloses a compound having a structure according to Formula I, wherein the definition of each group is as described in the specification. The invention also provides the use of the compounds in regulating immunity and inhibiting PD-1/PD-L1. 7. A pharmaceutical composition claim 1 , comprising (1) the compounds of or stereoisomers or tautomers thereof claim 1 , or pharmaceutically acceptable salts claim 1 , hydrates or solvates thereof; and (2) a pharmaceutically acceptable carrier.810-. (canceled)12. A method for treating diseases related to the activity or expression of PD-1/PD-L1 claim 1 , wherein the diseases are selected from the group consisting of tumors claim 1 , pathogen infections claim 1 , and diseases related to autoimmune responses; the method comprises:{'claim-ref': [{'@idref': 'CLM-00001', 'claim 1'}, {'@idref': 'CLM-00007', 'claim 7'}], 'administrating the compounds of or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts, hydrates or solvates thereof, or the pharmaceutical composition of to a subject in need thereof.'}13. The method of claim 12 , wherein the tumor is selected from the group consisting of melanoma claim 12 , renal cancer claim 12 , prostate cancer claim 12 , breast cancer claim 12 , colon cancer and lung cancer claim 12 , bone cancer claim 12 , pancreatic cancer claim 12 , skin cancer claim 12 , head or neck cancer claim 12 , skin or intraocular melanoma claim 12 , uterine cancer claim 12 , ovarian cancer claim 12 , rectal cancer claim 12 , anal cancer claim 12 , gastrointestinal cancer claim 12 , testicular cancer claim 12 , uterine cancer claim 12 , fallopian tube cancer claim 12 , endometrial cancer claim 12 , cervical cancer claim 12 , vaginal cancer claim 12 , vulva cancer claim 12 , Hodgkin's disease claim 12 , non-Hodgkin's lymphoma claim 12 , ...

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Номер записи: 51
07-02-2019 дата публикации

INDOLE AND INDAZOLE COMPOUNDS AND THERAPEUTIC USES THEREOF

Номер: US20190040016A1
Автор: MEREDDY Venkatram R.
Принадлежит:

Disclosed are Indole and Indazole derivatives, method for preparing these compounds, and methods for treating cancers. 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein A is a Caryl optionally substituted with 1-3 substituents selected from the group consisting of halogen claim 1 , Calkyl claim 1 , halogenCalkyl claim 1 , —OR claim 1 , —CN claim 1 , —NO claim 1 , —NRR claim 1 , —C(O)NRR claim 1 , and —NRC(O)R.5. (canceled)613. The compound of claim 1 , wherein Ris optionally substituted —C(O)—C-Ccarbocyclyl claim 1 , optionally substituted —C(O)-5-10 membered heterocyclyl claim 1 , optionally substituted —C(O)—Caryl claim 1 , and optionally substituted C(O)-5-10 membered heteroaryl.7. The compound of claim 6 , wherein Ris a 5-10 membered —C(O)—heterocyclyl optionally susbtituted with 1-3 substituents selected from the group consisting of halogen claim 6 , Calkyl claim 6 , halogenCalkyl claim 6 , —OR claim 6 , —CN claim 6 , —NO claim 6 , —NRR claim 6 , —C(O)NRR claim 6 , and —NRC(O)R.9. The compound of claim 1 , wherein Ris selected from the group consisting of C(O)H claim 1 , -—COOH claim 1 , —C(O)O(CH)—C(COR)═CHR claim 1 , and —C(O)O(CH)—C(COR)(OH)CH(OH)R.10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. The compound of claim 9 , wherein Ris C(O)O(CH)—C(COCH)═CHor —C(O)O(CH)—C(COCH)(OH)CH(OH).15. (canceled)16. The compound of claim 1 , wherein Rand Rare CH claim 1 , or Rand Rare —(CH)n-R.17. The compound of claim 1 , wherein Ris H and Ris COR.18. The compound of claim 17 , wherein Ris Caryl or —NH—Caryl claim 17 , each optionally substituted with 1-3 substituents selected from the group consisting of halogen claim 17 , Calkyl claim 17 , halogen claim 17 , —OR claim 17 , —CN claim 17 , —NO claim 17 , —NRR claim 17 , —C(O)NRR claim 17 , and —NRC(O)R.19. (canceled)20. The compound of claim 16 , wherein n is 1.21. The compound of claim 1 , wherein each Ris independently a Caryl optionally substituted with 1-3 substituents selected from the group ...

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Номер записи: 52
18-02-2021 дата публикации

METHODS AND COMPOSITIONS ASSOCIATED WITH THE GRANULOCYTE COLONY-STIMULATING FACTOR RECEPTOR

Номер: US20210046045A1
Автор: Grant Virginia H., Hudson Andrew R., Marschke Keith, Pedram Bijan, Pickens Jason C., Roach Steven L., Shen Yixing, Valdez Lino J., Van Oeveren Cornelis Arjan, Zhi Lin
Принадлежит:

Some embodiments include compositions and methods of using or identifying compounds that modulate the activity of the granulocyte colony-stimulating factor receptor (GCFR). Some embodiments include use of compounds to treat certain disorders, such as hematopoietic or neurological disorders. 120.-. (canceled)22. The compound of claim 21 , wherein W is NH.23. The compound of claim 21 , wherein X is N.27. The compound of claim 24 , wherein:{'sup': '3', 'sub': 1', '3, 'Ris selected from hydrogen, and an optionally substituted C-Calkyl;'}{'sup': '4', 'sub': 1', '6', '3', '8, 'Ris selected from an optionally substituted C-Calkyl, an optionally substituted C-Ccycloalkyl; and'}{'sup': '9', 'sub': 1', '6, 'Ris selected from an optionally substituted C-Calkyl, an optionally substituted arylalkyl, an optionally substituted arylalkenyl, an optionally substituted arylalkynyl, and an optionally substituted heteroarylalkyl.'}28. The compound of claim 27 , wherein:{'sup': '3', 'sub': 1', '3, 'Ris an optionally substituted C-Calkyl;'}{'sup': '4', 'sub': 1', '4, 'Ris an optionally substituted C-Calkyl; and'}{'sup': '9', 'sub': 1', '3, 'Ris selected from an optionally substituted C-Calkyl, an optionally substituted arylalkyl, an optionally substituted arylalkenyl, and an optionally substituted arylalkynyl.'}29. The compound of claim 28 , wherein Ris a C-Calkyl.30. The compound of claim 29 , wherein Ris methyl.31. The compound of claim 28 , wherein Ris a C-Calkyl substituted with hydroxy claim 28 , cyano claim 28 , or phenyl.32. The compound of claim 31 , wherein Ris a C-Calkyl substituted with hydroxy.35. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient. This application is a continuation of U.S. application Ser. No. 16/126,199 filed Sep. 10, 2018 which is a continuation of U.S. application Ser. No. 15/247,164 filed Aug. 25, 2016 now U.S. Pat. No. 10,111,859 issued Oct. 30, 2018 which is a continuation of U.S. application Ser. No. 14/ ...

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Номер записи: 53
12-02-2015 дата публикации

ArylSulfonamide-Based Matrix Metalloprotease Inhibitors

Номер: US20150045398A1
Автор: Ehrhardt Claus, McQuire Leslie Wighton, Rigollier Pascal, Rogel Olivier, Shultz Michael David, Tommasi Ruben Alberto
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula (I): 1. A compound selected from2-Chloro-5-(4-pyrrol-1-yl-benzoyl)-benzenesulfonamide;2-Chloro-5-(4-thiophen-2-yl-benzoyl)-benzenesulfonamide;2-Chloro-5-(4-thiophen-3-yl-benzoyl)-benzenesulfonamide;2-Chloro-5-(4-pyridin-3-yl-benzoyl)-benzenesulfonamide;2-Chloro-5-(4-pyridin-4-yl-benzoyl)-benzenesulfonamide;2-Chloro-5-[4-(2-chloro-pyridin-4-yl)-benzoyl]benzenesulfonamide;2-Chloro-5-(3-ethyl-1H-indazole-6-carbonyl)-benzenesulfonamide;2-Chloro-5-(3-methyl-1H-indazole-6-carbonyl)-benzenesulfonamide;2-Chloro-5-(3-isopropyl-1H-indazole-6-carbonyl)-benzenesulfonamide;5-(1-Benzyl-3-ethyl-1H-indazole-6-carbonyl)-2-chloro-benzenesulfonamide; and or', 'a pharmaceutically acceptable salt thereof., '2-Chloro-5-[3-(2-cyclopentyl-ethyl)-1H-indazole-6-carbonyl]-benzenesulfonamide;'}2. The compound of selected from2-Chloro-5-(4-thiophen-3-yl-benzoyl)-benzenesulfonamide and 'a pharmaceutically acceptable salt thereof.', '2-Chloro-5-(3-ethyl-1H-indazole-6-carbonyl)-benzenesulfonamide; or'}37-. (canceled)8. A method of inhibiting activity of MMP-2 claim 1 , and/or MMP-8 claim 1 , and/or MMP-9 claim 1 , and/or MMP-12 and/or MMP-13 in a subject claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the subject a therapeutically effective amount of the compound according to .'}9. A method of treating a disorder or a disease in a subject mediated by MMP-2 claim 1 , and/or MMP-8 claim 1 , and/or MMP-9 claim 1 , and/or MMP-12 and/or MMP-13 claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the subject a therapeutically effective amount of the compound according to .'}10. The method of claim 9 , wherein the disorder or the disease is selected from the group consisting of Alport syndrome claim 9 , asthma claim 9 , rhinitis claim 9 , chronic obstructive pulmonary diseases (COPD) claim 9 , arthritis claim 9 , atherosclerosis and restenosis claim 9 , cancer invasion and ...

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Номер записи: 54
06-02-2020 дата публикации

HEAT SHOCK PROTEIN 90 INHIBITORS

Номер: US20200039923A1
Автор: LIOU Jing-Ping, PAN Shiow-Lin, TENG Che-Ming
Принадлежит:

This disclosure is related to aromatic compounds of formula (I), and methods of their use in treating medical conditions associated with Heat Shock Protein-90 (HSP90), e.g., cancer. Compounds of formula (I) have the following structure: 2. The compound of claim 1 , wherein each of Rand Ris OH and Ris isopropyl.3. The compound of claim 2 , wherein X is CO and Y is N.6. The compound of claim 4 , wherein Z is phenyl and Ris —NHCO(CH)CONHOH or —CONH(CH)CONHOH.14. The compound of claim 1 , wherein X is CO claim 1 , NR claim 1 , or a bond and Y is CO claim 1 , SO claim 1 , or a bond.15. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.17. The method of claim 16 , wherein X is CO claim 16 , Y is N claim 16 , each of Rand Ris OH claim 16 , and Ris isopropyl.21. The method of claim 16 , wherein the medical condition is cancer.22. The method of claim 21 , wherein the cancer is breast cancer claim 21 , non-small cell lung cancer claim 21 , gastric cancer claim 21 , lymphoma claim 21 , or multiple myeloma.23. The method of claim 16 , wherein the compound is administered orally. This disclosure relates to the field of treating medical conditions associated with Heat shock protein 90 (HSP90) using compounds of formula (I). In particular, this disclosure relates to treating cancer with compounds of formula (I).Molecular chaperones guide polypeptides to fold correctly so that they lower the risk of protein assembly while exposing to the protein-rich intracellular environment. Heat shock protein 90 (HSP90), a molecular chaperone, functions as a stabilizer and activator of HSP90 client proteins, such as protein kinase B, cyclin-dependent kinase 4, and fins-like tyrosine kinase 3. Certain HSP90 client proteins, crucial in cell growth, are termed oncoproteins.HSP90 has become an attractive target due to its close connection with numerous client proteins. One of the advantages of inhibiting HSP90 is that the inhibition causes simultaneous ...

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Номер записи: 55
18-02-2021 дата публикации

E3 UBIQUITIN LIGASE AGONISTS, PHARMACEUTICAL COMPOSITIONS INCLUDING THE E3 UBIQUITIN LIGASE AGONISTS, RELATED METHODS OF USE

Номер: US20210047278A1
Автор: Bannister Thomas D., CLURMAN Bruce, HANDELI Shlomo, SCAMPAVIA Louis D., SPICER Timothy Patrick, Zheng Ning
Принадлежит:

E3 ubiquitin ligase agonists, pharmaceutical compositions including the E3 ubiquitin ligase agonists, and related methods of use are described. 122.-. (canceled)25. A method of treating an FBW7-mediated malignancy in an individual in need thereof , the method comprising administering to the individual in need thereof a therapeutically effective amount of an FBW7 agonist or a pharmaceutical composition comprising an FBW7 agonist , a stereoisomer , or a pharmaceutically acceptable salt thereof , the individual in need thereof having a mutated FBW7 protein.26. The method of claim 25 , wherein the FBW7 agonist is a compound according to27. The method of claim 25 , wherein the mutant FBW7 protein is a mutant FBW7 protein is a mutation selected from the group consisting of R465 claim 25 , R479 claim 25 , R505 claim 25 , R689 claim 25 , and combinations thereof claim 25 , relative to a wildtype FBW7 protein according to SEQ ID NO. 1.28. The method of claim 25 , wherein the FBW7-mediated malignancy is an FBW7-mediated cancer.29. The method of claim 28 , wherein the FBW7-mediated cancer is selected from the group consisting of colorectal carcinoma claim 28 , uterine endometrial carcinoma claim 28 , lymphoid leukemia claim 28 , myeloid leukemia claim 28 , bladder carcinoma claim 28 , stomach adenocarcinoma claim 28 , lung squamous cell carcinoma claim 28 , cervical squamous cell carcinoma claim 28 , and head and neck squamous cell carcinoma.30. The method of claim 25 , wherein administering the FBW7 agonist or the pharmaceutical composition to the individual in need thereof comprises contacting an FBW7 protein and an FBW7 substrate with the FBW7 agonist or the pharmaceutical composition claim 25 , and wherein the FBW7 substrate is an oncoprotein.31. The method of claim 30 , wherein the FBW7 substrate is selected from the group consisting of c-Myc claim 30 , n-Myc claim 30 , Notch claim 30 , cyclin E claim 30 , c-Jun claim 30 , PGC-1a claim 30 , SREBP1 claim 30 , SREBP2 claim ...

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Номер записи: 56
18-02-2021 дата публикации

SALT FORMS OF ORGANIC COMPOUND

Номер: US20210047279A1
Автор: LEE Jae Moon, SHIN Sunmi, YOO Sungeun
Принадлежит:

A salt compound of 4-(2-((4-bromophenyl)thio)acetamido)-1-phenethyl-1H-pyrazole-3-carboxylic acid is disclosed. Also disclosed are methods for making the salt compound and formulations of the salt compound into dosage forms for clinical use. 2. The salt compound of in which X is a potassium ion claim 1 , sodium ion claim 1 , calcium ion or a substituted ammonia molecule.3. The salt compound of claim 1 , in which X is a quaternary amine claim 1 , wherein the amine is selected from the group consisting of choline claim 1 , diethylamine claim 1 , dimethylamine claim 1 , L-lysine claim 1 , N claim 1 ,N′-dibenzylethylenediamine claim 1 , N-ethylglucamine claim 1 , 1-(2-hydroxyethyl)pyrrolidine claim 1 , N-(phenylmethyl)benzeneethaneamine claim 1 , ammonia claim 1 , magnesium acetate claim 1 , N-methylglucamine claim 1 , tromethamine claim 1 , 4-(2-hydroxyethyl)morpholine claim 1 , 2-(diethylamino)ethanol claim 1 , 2-dimethylamino-ethanol.4. The salt compound of in which X is potassium ion claim 1 , sodium ion or quaternary dimethylamine or quaternary diethylamine.5. The salt compound of claim 1 , in which m is 0.5 or 1.6. The salt compound of claim 4 , in which m is 0.5 or 1.7. The salt compound of claim 1 , that is a solvate further including 4-methyl-pentan-2-one claim 1 , ethanol or diisopropyl ether.8. The salt compound of claim 4 , that is a solvate further including ethanol or diisopropyl ether.10. The process of claim 9 , in which the organic solvent is 1 claim 9 ,1-dimethoxyethane claim 9 , acetonitrile claim 9 , ethanol claim 9 , 1 claim 9 ,2-dichloroethane claim 9 , benzonitrile claim 9 , ethyl acetate claim 9 , 1 claim 9 ,4-dioxane claim 9 , anisole claim 9 , heptane claim 9 , 2-butanol claim 9 , cumene claim 9 , hexane claim 9 , 2-propanol claim 9 , cyclohexane claim 9 , isopropyl acetate claim 9 , 4-methyl-pentan-2-one claim 9 , dichloromethane claim 9 , methanol claim 9 , acetone claim 9 , diisopropyl ether (DIPE) claim 9 , isobutyl acetate claim 9 , ...

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Номер записи: 57
18-02-2016 дата публикации

Heterocyclic Derivative and Pharmaceutical Drug

Номер: US20160046612A1
Автор: OTSU Hironori
Принадлежит: NIPPON SHINYAKU CO., LTD.

The present invention provides a novel heterocyclic derivative or a pharmaceutically acceptable salt thereof. For example, the present invention provides a heterocyclic derivative of the general formula [1] or its tautomer, or a pharmaceutically acceptable salt thereof: 2. The compound according to claim 1 , wherein the ring A is a group of formula [4] and Xis NH.3. The compound according to claim 1 , wherein Ris phenyl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-5-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalen-6-yl claim 1 , 2 claim 1 ,3-dihydro-1H-inden-4-yl claim 1 , 2 claim 1 ,3-dihydro-1H-inden-5-yl claim 1 , 1 claim 1 ,2-dihydrocyclobutabenzen-3-yl claim 1 , or 1 claim 1 ,2-dihydrocyclobutabenzen-4-yl claim 1 , and said phenyl is optionally substituted with one to three groups selected from the group consisting ofi) halogen,ii) alkyl optionally substituted with one to three halogens,iii) alkoxy, andiv) cyano.4. The compound according to claim 1 , wherein Ris phenyl and said phenyl is optionally substituted with one to three groups selected from the group consisting ofi) halogen,ii) alkylsulfonyl,iii) alkoxy optionally substituted with alkoxy,iv) alkynyl optionally substituted with alkoxyalkyl or cycloalkyl, andv) alkyl optionally substituted with one to three groups selected from the group consisting of halogen, alkoxy, alkoxyalkoxy, cycloalkyl and phenyl.5. The compound according to claim 1 , whereinthe ring A is a group of formula [4],{'sup': '1', 'Xis NH,'}{'sup': '2', 'claim-text': i) hydrogen,', 'ii) alkyl optionally substituted with a group selected from the group consisting of halogen, monoalkylamino, dialkylamino, monoalkylaminocarbonyl, dialkylaminocarbonyl, a saturated cyclic aminocarbonyl, alkoxy, alkoxyalkoxy and alkylcarbonyloxy,', 'iii) cycloalkyl optionally substituted with alkyl optionally substituted with one to three halogens,', 'iv) alkoxy,', 'v) a saturated heterocyclic group optionally ...

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Номер записи: 58
01-05-2014 дата публикации

NOVEL 1-SUBSTITUTED INDAZOLE DERIVATIVE

Номер: US20140121244A1
Автор: Nakai Yoko, Usui Shinya, YAMAGUCHI Hiroki
Принадлежит:

A medicament for treating diseases associated with cholinergic properties in the central nervous system (CNS) and/or peripheral nervous system (PNS), diseases associated with smooth muscle contraction, endocrine disorders, neurodegenerative disorders and the like, which comprises a compound of Formula (I): 123.-. (canceled)24. A compound selected from the group consisting of:{'sup': '2', 'sub': '3', 'N-(trans-4-methoxycyclohexyl)-4-[5-(H)methyl-1H-indazol-1-yl]piperidine-1-carboxamide;'}N-(tetrahydro-2H-pyran-4-yl)-4-[5-(trifluoromethoxy)-1H-indazol-1-yl]piperidine-1-carboxamide; and{'sup': '2', 'sub': '3', '4-(5-methyl-1H-indazol-1-yl)-N-{trans-4-[(H)methoxy]cyclohexyl}piperidine-1-carboxamide,'}or a pharmaceutically acceptable salt thereof.25. The compound of claim 24 , wherein the compound is N-(trans-4-methoxycyclohexyl)-4-[5-(H)methyl-1H-indazol-1-yl]piperidine-1-carboxamide claim 24 , or a pharmaceutically acceptable salt thereof.26. The compound of claim 24 , wherein the compound is N-(tetrahydro-2H-pyran-4-yl)-4-[5-(trifluoromethoxy)-1H-indazol-1-yl]piperidine-1-carboxamide claim 24 , or a pharmaceutically acceptable salt thereof.27. The compound of claim 24 , wherein the compound is 4-(5-methyl-1H-indazol-1-yl)-N-{trans-4-[(H)methoxy]cyclohexyl}piperidine-1-carboxamide claim 24 , or a pharmaceutically acceptable salt thereof.28. A method for treating CIAS (cognitive impairment associated with schizophrenia) comprising administering a therapeutically effective amount of a compound selected from the group consisting of:{'sub': '3', 'N-(trans-4-methoxycyclohexyl)-4-[5-(2H)methyl-1H-indazol-1-yl]piperidine-1-carboxamide;'}N-(tetrahydro-2H-pyran-4-yl)-4-[5-(trifluoromethoxy)-1H-indazol-1-yl]piperidine-1-carboxamide; and{'sup': '2', 'sub': '3', '4-(5-methyl-1H-indazol-1-yl)-N-{trans-4-[(H)methoxy]cyclohexyl}piperidine-1-carboxamide,'}or a pharmaceutically acceptable salt thereof.29. The method of claim 28 , wherein the compound is N-(trans-4-methoxycyclohexyl)-4 ...

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Номер записи: 59
26-02-2015 дата публикации

Bivalent ampa receptor positive allosteric modulators

Номер: US20150057248A1
Автор: Cheng Z. Wang, Haijun Chen, Jia Zhou, Kenneth M. Johnson
Принадлежит: University of Texas System

Embodiments of the invention are directed to compounds that are positive allosteric modulators of AMPA receptors.

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Номер записи: 60
25-02-2021 дата публикации

WORKFLOW FOR GENERATING COMPOUNDS WITH BIOLOGICAL ACTIVITY AGAINST A SPECIFIC BIOLOGICAL TARGET

Номер: US20210057050A1
Автор: Aliper Aleksandr, Ivanenkov Yan, Polykovskiy Daniil, Zavoronkovs Aleksandrs
Принадлежит:

A computer-implemented method can include: receiving input of a biological target; receiving a generative model (e.g., tensorial reinforcement learning (GENTRL) model or other model) trained with reference compounds, wherein the reference compounds include: general compounds, compounds that modulate the biological target, and compounds that modulate biomolecules other than the biological target; generating structures of generated compounds with the generative model; prioritizing structures of generated compounds based on at least one criteria; processing prioritized chemical structures of the generated compounds through a Sammon mapping protocol to obtain hit structures; and providing chemical structures of the hit structures. One or more non-transitory computer readable media are provided that store instructions that in response to being executed by one or more processors, cause a computer system to perform operations, the operations comprising performing the computer methods described herein for providing chemical structure of hit structures generated by the generative model. 1. A computer-implemented method , comprising:receiving input of a biological target or ligand;receiving input of properties of a generated compound;receiving at least one generative model trained with reference compounds;generating structures of generated compounds with each generative model, wherein the generated compounds are designed to interact with the biological target and/or correlate with structural features of the ligand;prioritizing structures of the generated compounds of each generative model based on at least one reward criteria;processing prioritized chemical structures of the generated compounds through a Sammon mapping protocol to obtain hit structures; andproviding chemical structures of the hit structures.2. The method of claim 1 , further comprising:receiving the reference compounds; andtraining the generative model with the reference compounds.3. The method of claim 1 , ...

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Номер записи: 61
02-03-2017 дата публикации

HISTONE DEACETYLASE INHIBITORS

Номер: US20170057956A1
Автор: Chang Jang-Yang, LIOU Jing-Ping, Wang Jia-Yi, Yen Yun
Принадлежит:

Fused bicycle indol, indoline, azoindole, or azoindoline compounds of Formula (I) set forth herein. Also disclosed are pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing the same. Further disclosed is a method for treating cancer, e.g., glioma, prostate cancer, and colorectal cancer, with these compounds. 2. The compound of claim 1 , wherein A is a pyridine ring or a pyrimidine ring claim 1 , and X is CH claim 1 , C claim 1 , or N.4. The compound of claim 1 , wherein A is a pyridine ring optionally mono claim 1 , di claim 1 , or tri-substituted with halo claim 1 , hydroxyl claim 1 , nitro claim 1 , cyano claim 1 , amino claim 1 , C-Calkylamino claim 1 , C-Cdialkylamino claim 1 , C-Calkoxy claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , aryl claim 1 , heteroaryl claim 1 , C-Ccycloalkyl claim 1 , C-Ccycloalkenyl claim 1 , C-Cheterocycloalkyl claim 1 , or C-Cheterocycloalkenyl claim 1 , in which alkenyl is optionally substituted with C(O)OR′ claim 1 , C(O)NR′R″ claim 1 , R′ being H or C-Calkyl and R″ being H claim 1 , OH claim 1 , C-Calkyl claim 1 , or aryl; and X is C or CH.5. The compound of claim 4 , wherein Ris SOR claim 4 , Rbeing naphthalenyl or phenyl claim 4 , each of which is optionally mono- claim 4 , di claim 4 , or tri-substituted with halo claim 4 , hydroxyl claim 4 , nitro claim 4 , cyano claim 4 , amino claim 4 , C-Calkylamino claim 4 , C-Cdialkylamino claim 4 , C-Calkoxy claim 4 , C-Calkyl claim 4 , C-Calkenyl claim 4 , C-Calkynyl claim 4 , aryl claim 4 , heteroaryl claim 4 , C-Ccycloalkyl claim 4 , C-Ccycloalkenyl claim 4 , C-Cheterocycloalkyl claim 4 , or C-Cheterocycloalkenyl claim 4 , alkenyl being optionally substituted with C(O)OR′″ claim 4 , in which R′″ is H or C-Calkyl.6. The compound of claim 5 , wherein Ris phenyl optionally mono claim 5 , di claim 5 , or tri-substituted with halo claim 5 , nitro claim 5 , cyano claim 5 , amino claim 5 , C-Calkylamino claim 5 , C- ...

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Номер записи: 62
04-03-2021 дата публикации

AROMATIC VINYL OR AROMATIC ETHYL DERIVATIVE, PREPARATION METHOD THEREFOR, INTERMEDIATE, PHARMACEUTICAL COMPOSITION, AND APPLICATION

Номер: US20210061755A1
Автор: He Min, Wang Yuguang, WU Tianzhi, Zhang Nong
Принадлежит:

Disclosed in the present invention are an aromatic vinyl or aromatic ethyl derivative, a preparation method therefor, an intermediate, a pharmaceutical composition, and an application. The aromatic vinyl or aromatic ethyl derivative in the present invention is as represented by general formula (I). The aromatic vinyl or aromatic ethyl derivative in the present invention has an obvious inhibitory effect on PD-1/PD-L1, is a very effective small-molecule PD-1/PD-L1 inhibitor, and can effectively alleviate or treat relevant diseases such as cancer. 15. (canceled)16. A pharmaceutical composition claim 1 , which comprises a therapeutically and/or prophylactically effective amount of the aromatic vinyl or aromatic ethyl derivative represented by general formula (I) claim 1 , the pharmaceutically acceptable salt claim 1 , the metabolite claim 1 , the metabolic precursor or the prodrug thereof as defined in claim 1 , and a pharmaceutically acceptable carrier and/or a diluent.17. A method for inhibiting PD-1 and/or PD-L1 in a subject in need thereof claim 1 , comprising administering a therapeutically effective amount of the aromatic vinyl or aromatic ethyl derivative represented by general formula (I) claim 1 , the pharmaceutically acceptable salt claim 1 , the metabolite claim 1 , the metabolic precursor or the prodrug thereof as defined in to the subject.18. A method for preventing claim 1 , alleviating or treating cancer claim 1 , infection claim 1 , autoimmune diseases or related diseases thereof in a subject in need thereof claim 1 , comprising administering a therapeutically effective amount of the aromatic vinyl or aromatic ethyl derivative represented by general formula (I) claim 1 , the pharmaceutically acceptable salt claim 1 , the metabolite claim 1 , the metabolic precursor or the prodrug thereof as defined in to the subject.19. The method as defined in claim 18 , wherein claim 18 , the cancer is one or more selected from lung cancer claim 18 , esophageal cancer ...

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Номер записи: 63
20-02-2020 дата публикации

ANTI-FIBROTIC COMPOUNDS

Номер: US20200055814A1
Автор: Miller Thomas, Papaioannou Nikolaos
Принадлежит:

Provided herein are anti-fibrotic compounds, in particular those of Formula (I), that inhibit the TGF-beta signaling pathway. Also provided are pharmaceutical compositions comprising the anti-fibrotic compounds, and methods of treating diseases or conditions associated with fibrosis, inflammation, and benign or malignant neoplastic diseases in a subject by administering a compound KIN or composition described herein. (Formula (I)) 235-. (canceled)36. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , whereinG is hydrogen;m is H or 2; and{'sup': '6', 'each occurrence of Ris, independently, F or Cl.'}37. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '7', 'G is C(O)R;'}m is 0;{'sup': 7', '9, 'Ris NHR; and'}{'sup': '9', 'Ris tetrazolyl, pyridinyl, pyrazolyl, imidazolyl, or triazolyl, each of which is optionally substituted with up to two alkyl groups.'}40. The compound of claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , whereinX is O;{'sup': '10', 'Y is NR; and'}{'sup': '10', 'sub': '1-4', 'Ris Calkyl.'}41. The compound of claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein{'sup': '10', 'X is NR; and'}Y is O.42. The compound of claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , wherein Rand Rtogether with the carbon atom to which they are attached form a carbonyl.44. A compound selected from the group consisting of:(E)-N-(2-fluorophenyl)-3-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)acrylamide (1);(E)-3-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)-N-(2-(5-methyl-1H-1,2,4-triazol-3-yl)phenyl)acrylamide (2);(E)-N-(2-chlorophenyl)-3-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)acrylamide (3);(E)-N-(2-bromophenyl)-3-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)acrylamide (4);(E)-3-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)-N-(o-tolyl)acrylamide (5);(E)-N-(2-cyanophenyl)-3-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)acrylamide (6);(E)-N-(3,4-dichlorophenyl)-3-(3- ...

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Номер записи: 64
05-03-2015 дата публикации

Viral Polymerase Inhibitors

Номер: US20150065445A1
Автор: Bond Silas, Draffan Alistair George, Halim Rosliana, Harding Michael, Jeynes Tyrone Pieter
Принадлежит:

The present invention relates to viral polymerase inhibitors of formula (I) or salts, N-oxides, solvates, hydrates, racemates, enantiomers or isomers thereof, processes for their preparation and their use in the treatment of Flaviviridae viral infections such as Hepatitis C virus (HCV) infections. 2. A compound according to wherein Ris an optionally substituted oxetane or azetidine ring.4. A compound according to any one of to wherein (CH)is an optionally substituted methylenyl claim 1 , ethylenyl or propylenyl moiety.5. A compound according to selected from the group consisting of:3) 5-cyclopropyl-N-methyl-2-(4-methylphenyl)-6-{(methylsulfonyl)[2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide;4) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[3-(oxetan-2-yl)propyl]amino}-2H-indazole-3-carboxamide;5) 5-cyclopropyl-N-methyl-2-(5-methylpyridin-2-yl)-6-{(methylsulfonyl)[2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide;6) 6-{[2-(azetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide;7) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(1-methylazetidin-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;8) 6-{[2-(1-acetylazetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide;9) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(2-methyloxetan-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;10) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide;11) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(3-methyloxetan-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;12) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[(3-methyloxetan-3-yl)methyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide;13) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{(methylsulfonyl)[2-(oxetan-2-yl)ethyl]amino}-2H-indazole-3-carboxamide;14) 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl- ...

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Номер записи: 65
22-05-2014 дата публикации

MEDICAMENT FOR LIVER REGENERATION AND FOR TREATMENT OF LIVER FAILURE

Номер: US20140141510A1
Автор: Wuestefeld Torsten, Zender Lars
Принадлежит:

The present invention relates to the use of a compound which inhibits the activity of MKK4 as a medicament for the treatment of a patient suffering from an impaired liver function, to the use of a compound as a medicament for the treatment of liver failure, including acute/fulminant or chronic liver failure and/or for increasing the regeneration of liver tissue in a patient. 1. Compound , which is an inhibitor of the activity of MKK4 , MKK4 being encoded by the mRNA of SEQ ID NO: 1204 , for use as a medicament in the treatment of liver failure and/or for the protection of hepatocytes against apoptosis and/or for the regeneration of hepatocytes.2. Compound according to claim 1 , characterized in that the compound is an siRNA containing an oligonucleotide having a nucleotide sequence hybridizing under physiological conditions to the mRNA of SEQ ID NO: 1204.3. Compound according to claim 2 , characterized in that the oligonucleotide is selected from the group comprising miR-15b claim 2 , miR-24 claim 2 , miR-25 claim 2 , miR-141 claim 2 , and SEQ ID NO: 1 to SEQ ID NO: 1203.4. Compound according to claim 2 , characterized in that the oligonucleotide is comprised as a first section in a nucleic acid construct which contains a second section which is reverse complementary to the first section.5. Compound according to claim 2 , characterized in that the oligonucleotide is arranged under the control of a promoter in an expression cassette.6. Compound according to claim 2 , characterized in that the oligonucleotide is contained in a liposome formulation and/or in a viral vector which is packaged in a viral particle or in a virus-like particle.7. Compound according to claim 1 , characterized in that the compound is selected from the group consisting of SP600125 claim 1 , myricitine claim 1 , Genistein claim 1 , PD98059 claim 1 , and the compounds of Table 1.8. Compound according to claim 1 , characterized in that the compound is formulated as liposomes or lipid nanoparticles ...

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Номер записи: 66
28-02-2019 дата публикации

COMPOSITIONS AND METHODS FOR MODULATING FARNESOID X RECEPTORS

Номер: US20190062283A1
Автор: Chianelli Donatella, LI Runyan, MOLTENI Valentina, Nelson John, Roland Jason Thomas, RUCKER Paul Vincent, Tully David Charles, Wang Xiaoyang, Waykole Liladhar Murlidhar, ZHANG Yubo, ZHOU Bo
Принадлежит:

The present invention relates to compounds of Formula I, 1. A method for preparing 4-((N-benzyl-8-chloro-1-methyl-1 ,4-dihydrochromeno[4 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid meglumine monohydrate , comprising contacting 4-((N-benzyl-8-chloro-1-methyl-1 ,4-dihydrochromeno[4 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid in a solvent with meglumine in water solution under suitable conditions , thereby providing 4-((N-benzyl-8-chloro-1-methyl-1 ,4-dihydrochromeno[4 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid meglumine monohydrate.2. The method of claim 1 , comprising adding said meglumine in water solution to a suspension of said 4-((N-benzyl-8-chloro-1-methyl-1 claim 1 ,4-dihydrochromeno[4 claim 1 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid in acetone.3. The method of claim 1 , wherein said 4-((N-benzyl-8-chloro-1-methyl-1 claim 1 ,4-dihydrochromeno[4 claim 1 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid meglumine monohydrate has a dehydration point at about 71° C. by differential scanning calorimetry.4. The method of claim 1 , further comprising heating said 4-((N-benzyl-8-chloro-1-methyl-1 claim 1 ,4-dihydrochromeno[4 claim 1 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid meglumine monohydrate at a temperature ranging from 60-90° C. under suitable conditions claim 1 , thereby providing a 4-((N-benzyl-8-chloro-1-methyl-1 claim 1 ,4-dihydrochromeno[4 claim 1 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid meglumine salt.5. The method of claim 4 , comprising heating said 4-((N-benzyl-8-chloro-1-methyl-1 claim 4 ,4-dihydrochromeno[4 claim 4 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid meglumine monohydrate at about 80° C.6. The method of claim 5 , wherein said 4-((N-benzyl-8-chloro-1-methyl-1 claim 5 ,4-dihydrochromeno[4 claim 5 ,3-c]pyrazole-3-carboxamido)methyl)benzoic acid meglumine salt has a melting point of about 167.5° C. by differential scanning calorimetry.7. The method of claim 5 , wherein said 4-((N-benzyl-8-chloro-1-methyl-1 claim 5 ...

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Номер записи: 67
28-02-2019 дата публикации

HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF

Номер: US20190062321A1
Автор: Allen Daniel R., Breccia Perla, Bürli Roland W., Dominguez Celia, Haughan Alan F., Hughes Samantha J., Jarvis Rebecca E., Luckhurst Christopher A., Muñoz-Sanjuán Ignacio, Penrose Stephen D., Raphy Gilles, Saville-Stones Elizabeth A., Stott Andrew J., Vater Huw D., Wall Michael, Wishart Grant
Принадлежит:

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, or pharmaceutically acceptable salts thereof, compositions thereof, and methods of their use. 151.-. (canceled)53. (canceled)54. The method of claim 52 , wherein said at least one histone deacetylase is HDAC4.55. The method of claim 52 , wherein said condition or disorder involves a neurodegenerative pathology.56. The method of claim 52 , wherein said condition or disorder is Huntington's disease.64. A method for treating a condition or disorder mediated by at least one histone deacetylase in a patient in need thereof comprising administering to said patient a therapeutically effective amount of a compound claim 52 , or a pharmaceutically acceptable salt thereof claim 52 , selected from:(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-1-phenyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-1-(o-tolyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-5-(3-Fluoro-2-methyl phenyl)-1-(2-fluorophenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-1-(3-Chlorophenyl)-5-(3-fluoro-2-methylphenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-5-(3-Fluoro-2-methylphenyl)-1-(4-fluorophenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-5-(3-Fluoro-2-methylphenyl)-1-(3-fluorophenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-1-(2-Chlorophenyl)-5-(3-fluoro-2-methylphenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-1-(4-Chlorophenyl)-5-(3-fluoro-2-methylphenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-5-(3-Fluoro-2-methyl phenyl)-N-hydroxy-1-(p-tolyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-1-(3-Chloro-2-fluorophenyl)-5-(3-fluoro-2-methylphenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5-carboxamide;(S)-1-(2,6-Difluorophenyl)-5-(3-fluoro-2-methylphenyl)-N-hydroxy-1,4,5,6-tetrahydrocyclopenta[ ...

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Номер записи: 68
09-03-2017 дата публикации

Combinations for the treatment of neuroblastoma

Номер: US20170065582A1
Автор: David Wesley Anderson, Gang Li, Garrett M. Brodeur, Radhika IYER, Zachary Dolph Hornby
Принадлежит: Ignyta Inc

Disclosed are methods of treating neuroblastoma in a cancer patient by administration of a Trk inhibitor in combination with one more chemotherapeutic agents. Also disclosed are pharmaceutical compositions comprising a Trk inhibitor and one or more chemotherapeutic agents.

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Номер записи: 69
08-03-2018 дата публикации

INDAZOLE DERIVATIVES USEFUL AS GLUCAGON RECEPTOR ANTAGONISTS

Номер: US20180065934A1
Автор: Gaul Micheal, Lu Tianbao, Song Fengbin, Xu Guozhang, Yang Shyh-Ming, Zhang Rui
Принадлежит:

The present invention is directed to indazole derivatives, pharmaceutical compositions containing them and their use in the treatment and/or prevention of disorders and conditions ameliorated by antagonizing one or more glucagon receptors, including for example metabolic diseases such as Type II diabetes mellitus and obesity. 2. A compound of claim 1 , wherein{'sup': '1', 'sub': '1-2', 'Ris selected from the group consisting of phenyl, —(Calkyl)-phenyl, naphthyl, thienyl, benzofuranyl, benzothienyl, indazolyl, quinolinyl, pyrazolyl and pyridyl;'}{'sub': 1-6', '1-2', '1-4', '1-2, 'wherein the phenyl, naphthyl, thienyl, benzofuranyl, benzothienyl, indazolyl, quinolinyl, pyrazolyl or pyridyl whether alone or as part of a substituent group is optionally substituted with one to two substituents independently selected from the group consisting of halogen, Calkyl, fluorinated Calkyl, Calkoxy and fluorinated Calkoxy.'}a is in integer from 0 to 2;{'sup': '2', 'sub': 1-2', '1-2', '1-2', '1-2, 'each Ris independently selected from the group consisting of halogen, Calkyl, fluorinated Calkyl, Calkoxy and fluorinated Calkoxy;'}{'sup': '4', 'sub': 1-6', '1-4', '1-2', '1-4', '3-6', '1-2', '3-6', '1-2, 'Ris selected from the group consisting of Calkyl, fluorinated Calkyl, —(Calkyl)-O—(Calkyl), Ccycloalkyl, —(Calkyl)-Ccycloalkyl, phenyl and —(Calkyl)-phenyl;'}{'sub': 1-6', '1-2', '1-4', '1-2, 'wherein the phenyl, whether alone or as part of a substituent group is optionally substituted with one or to two substituents independently selected from the group consisting of halogen, Calkyl, fluorinated Calkyl, Calkoxy and fluorinated Calkoxy;'}Z is selected from the group consisting of C and N;or a stereoisomer or pharmaceutically acceptable salt thereof.3. A compound of claim 1 , wherein{'sup': '1', 'Ris selected from the group consisting of phenyl, naphthyl, thienyl, benzofuranyl, benzothienyl, pyrazolyl, indazolyl and quinolinyl;'}{'sub': 1-6', '1-2', '1-2', '1-2, 'wherein the phenyl, ...

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Номер записи: 70
08-03-2018 дата публикации

INDAZOLE DERIVATIVES USEFUL AS GLUCAGON RECEPTOR ANTAGONISTS

Номер: US20180065955A1
Автор: Gaul Micheal, Lu Tianbao, Song Fengbin, Xu Guozhang, Yang Shyh-Ming, Zhang Rui
Принадлежит:

The present invention is directed to indazole derivatives, pharmaceutical compositions containing them and their use in the treatment and/or prevention of disorders and conditions ameliorated by antagonizing one or more glucagon receptors, including for example metabolic diseases such as Type II diabetes mellitus and obesity. 2. A compound of claim 1 , wherein{'sup': '1', 'Ris selected from the group consisting of phenyl, naphthyl, thienyl, benzofuranyl, benzothienyl, indazolyl, quinolinyl, pyrazolyl and pyridyl;'}{'sub': 1-6', '1-2', '1-2', '1-2, 'wherein the phenyl, naphthyl, thienyl, benzofuranyl, benzothienyl, indazolyl, quinolinyl, pyrazolyl or pyridyl whether alone or as part of a substituent group is optionally substituted with one to two substituents independently selected from the group consisting of halogen, Calkyl, fluorinated Calkyl, Calkoxy and fluorinated Calkoxy.'}a is in integer from 0 to 2;{'sup': '2', 'sub': 1-2', '1-2', '1-2', '1-2, 'each Ris independently selected from the group consisting of halogen, Calkyl, fluorinated Calkyl, Calkoxy and fluorinated Calkoxy;'}{'sup': '4', 'sub': 1-6', '1-4', '1-2', '1-4', '3-6', '1-2', '3-6', '1-2, 'Ris selected from the group consisting of Calkyl, fluorinated Calkyl, —(Calkyl)-O—(Calkyl), Ccycloalkyl, —(Calkyl)-Ccycloalkyl, phenyl and —(Calkyl)-phenyl;'}{'sub': 1-6', '1-2', '1-4', '1-2, 'wherein the phenyl, whether alone or as part of a substituent group is optionally substituted with one or to two substituents independently selected from the group consisting of halogen, Calkyl, fluorinated Calkyl, Calkoxy and fluorinated Calkoxy;'}{'u': {'@style': 'single', 'H'}, 'Z is selected from the group consisting of C and N;'}or a stereoisomer or pharmaceutically acceptable salt thereof.3. A compound of claim 1 , wherein{'sup': '1', 'Ris selected from the group consisting of phenyl, naphthyl, thienyl, pyridyl, benzofuranyl, benzothienyl, indazolyl, pyrazolyl and quinolinyl;'}{'sub': 1-6', '1-2', '1-2', '1-2, 'wherein ...

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Номер записи: 71
09-03-2017 дата публикации

NAPHTHYLAMIDE COMPOUND, PREPARATION METHOD AND USE THEREOF

Номер: US20170066723A1
Автор: DING Jian, DUAN Wenhu, Lv Yongcong, Xie Hua
Принадлежит:

The present invention relates to a naphthylamide compound of the structure as represented by formula (I), medicinal salts, prodrugs and hydrates or solvates thereof, and also relates to a method of preparing the compounds, pharmaceutical compositions comprising the compounds and the uses thereof as protein tyrosine kinase inhibitors, particularly as VEGFR-2 inhibitors, in preparing drugs for preventing and treating diseases related to abnormal angiogenesis. 7. A pharmaceutical composition comprising a therapeutically effective amount of one or more of compounds claim 1 , pharmaceutically acceptable salts claim 1 , prodrugs claim 1 , hydrates and solvates thereof of claim 1 , and optionally a pharmaceutically acceptable carrier.8. Use of one or more of compounds claim 1 , pharmaceutically acceptable salts claim 1 , prodrugs claim 1 , hydrates and solvates thereof of in the preparation of medicaments for preventing and/or treating abnormal angiogenesis-related diseases claim 1 , preferably as protein tyrosine kinase inhibitors claim 1 , especially as VEGFR-2 inhibitors.9. The use of claim 8 , wherein claim 8 , the abnormal angiogenesis-related disease is selected from the group consisting of tumor claim 8 , rheumatoid arthritis claim 8 , age-related macular degeneration and psoriasis.10. The use of claim 9 , wherein claim 9 , the tumor includes lung cancer claim 9 , breast cancer claim 9 , colon cancer claim 9 , prostate cancer claim 9 , pancreas cancer claim 9 , stomach cancer claim 9 , liver cancer claim 9 , ovarian cancer claim 9 , renal cancer claim 9 , glioma claim 9 , melanoma claim 9 , pancreatic cancer claim 9 , head and neck cancer claim 9 , bladder cancer claim 9 , cervical cancer claim 9 , cholangiocarcinoma claim 9 , nasopharyngeal cancer claim 9 , thyroid cancer claim 9 , osteosarcoma claim 9 , synovial sarcoma claim 9 , rhabdomyosarcoma claim 9 , fibrosarcoma claim 9 , leiomyosarcoma claim 9 , myeloma and lymphoma.11. Use of the pharmaceutical ...

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Номер записи: 72
09-03-2017 дата публикации

ANALOGS OF FEXARAMINE AND METHODS OF MAKING AND USING

Номер: US20170066724A1
Автор: Atkins Annette, Baiga Thomas J., Downes Michael, Evans Ronald M., Fang Sungsoon, Keana John F.W., Liddle Christopher, Suh Jae Myoung, Yu Ruth T.
Принадлежит:

Novel compounds having a formula 3. The compound of claim 1 , wherein Ris deuterium.4. The compound of claim 2 , wherein Ror Ror both are halogen.5. The compound of claim 4 , wherein Ror Ror both are F.8. The compound of claim 1 , wherein RC comprises a nitrogen-containing heteroaryl ring.9. The compound of claim 8 , wherein RC is selected from pyridine claim 8 , pyrazole claim 8 , pyrrole claim 8 , imidazole claim 8 , oxazole claim 8 , isoxazole claim 8 , thiazole claim 8 , isothiazole claim 8 , triazole claim 8 , pyrimidine claim 8 , pyrazine claim 8 , triazine claim 8 , benzopyrazole claim 8 , benzimidazole claim 8 , indole claim 8 , quinoline claim 8 , indazole claim 8 , purine claim 8 , quinoxaline claim 8 , or acridine.11. The compound of claim 10 , wherein Z is N; R claim 10 , R claim 10 , Rand Rare all H; Ris methyl; or a combination thereof.13. The compound of claim 12 , wherein Rand Rare both methyl.17. A compound claim 12 , selected frommethyl (E)-3-(3-(N-(4-(1-methyl-1H-indazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;methyl (E)-3-(3-((1R,2S,4S)—N-(4-(1-methyl-1H-indazol-5-yl)benzyl)bicyclo[2.2.1]heptane-2-carboxamido)phenyl)acrylate;methyl (E)-3-(3-(1-methyl-N-(4-(1-methyl-1H-indazol-5-yl)benzyl)piperidine-4-carboxamido)phenyl)acrylate;methyl (E)-3-(5-(N-((1-methyl-1H-benzo[f]indazol-8-yl)methyl)cyclohexanecarboxamido)pyridin-3-yl)acrylate;methyl (E)-3-(3-fluoro-5-((1S,2R,4R)—N-((1-methyl-1H-benzo[1]indazol-8-yl)methyl)bicyclo[2.2.1]heptane-2-carboxamido)phenyl)acrylate;methyl (E)-3-(3-(N-((9-fluoro-1-methyl-1H-benzo[f]indazol-8-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;methyl (E)-3-(3-((1R,4S)—N-((9-fluoro-1-methyl-1H-benzo[f]indazol-8-yl)methyl)bicyclo[2.2.1]heptane-2-carboxamido)phenyl)acrylate;methyl (E)-3-(3-(N-((9-fluoro-1-methyl-1H-benzo[f]indazol-8-yl)methyl)-1-methylpiperidine-4-carboxamido)phenyl)acrylate;methyl (E)-3-(5-(N-((9-fluoro-1-methyl-1H-benzo[f]indazol-8-yl)methyl)cyclohexanecarboxamido)pyridin-3-yl)acrylate;methyl ( ...

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Номер записи: 73
11-03-2021 дата публикации

PESTICIDAL COMPOUNDS

Номер: US20210070713A1
Автор: Adisechan Ashokkumar, CHAUDHURI Rupsha, Narine Arun, SAMBASIVAN Sunderraman, VYAS Devendra
Принадлежит:

The present invention relates to the compounds of formula (I), and the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof wherein the variables are defined according to the description, formula (I). The compounds of formula (I), as well as the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof, are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds. 2. The compound of formula I according to claim 1 , wherein W is O claim 1 , Ais CR claim 1 , Ais CR claim 1 , and Ais N.3. The compound of formula I according to claim 1 , wherein W is N claim 1 , Ais CR claim 1 , Ais CR claim 1 , and Ais N.4. The compound of formula I according to claim 1 , wherein W is O claim 1 , Ais CR claim 1 , Ais CR claim 1 , and Ais CR.5. The compound of formula I according to claim 1 , wherein W is N claim 1 , Ais CR claim 1 , Ais CR claim 1 , and Ais CR.6. The compound of formula I according to claim 1 , wherein W is N claim 1 , Ais N claim 1 , Ais N claim 1 , and Ais CR.7. The compound of formula I according to claim 1 , wherein W is S(═O) claim 1 , Ais CR claim 1 , Ais CR claim 1 , and Ais CR.10. A composition comprising one compound of formula I according to claim 1 , an N-oxide or an agriculturally acceptable salt thereof claim 1 , and a further active substance.11. A method for combating or controlling invertebrate pests claim 1 , comprising contacting said pest or its food supply claim 1 , habitat or breeding grounds with a pesticidally effective amount of at least one compound according to .12. A method for protecting growing plants from attack or infestation by invertebrate pests claim 1 , comprising contacting a plant claim 1 , or soil or ...

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Номер записи: 74
12-03-2015 дата публикации

UREA DERIVATIVES AND USES THEREOF

Номер: US20150072986A1
Автор: Enlow Elizabeth, Feutrill John Thomas, KIM Jinsoo, Nguyen Minh Ngoc, Nowak Pawel Wojciech, Ong Winston Zapanta
Принадлежит:

The present invention provides novel compounds of any one of Formulae (I)-(III), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof. 23. The compound of claim 1 , wherein:{'sup': 'A', 'Xis C;'}{'sup': 'B', 'Xis N;'}{'sup': 'C', 'Xis N; and'}{'sup': 'D', 'Xis CH.'}24. The compound of claim 1 , wherein:{'sup': 'A', 'Xis N;'}{'sup': 'B', 'Xis C;'}{'sup': 'C', 'Xis N; and'}{'sup': 'D', 'Xis CH.'}25. The compound of claim 1 , wherein:{'sup': 'A', 'Xis C;'}{'sup': 'B', 'Xis C;'}{'sup': 'C', 'Xis NH; and'}{'sup': 'D', 'Xis CH.'}26. The compound of claim 1 , wherein at least one instance of Ris halogen or substituted or unsubstituted Calkyl.28. The compound of claim 27 , wherein Lis —O—.29. The compound of claim 27 , wherein Lis —N(R)—.30. The compound of claim 27 , wherein Lis —C(═O)—N(R)— claim 27 , —S(═O)—N(R)— claim 27 , —S(═O)—N(R)— claim 27 , —N(R)—C(═O)— claim 27 , —N(R)—S(═O)— claim 27 , or —N(R)—S(═O)—.31. The compound of claim 27 , wherein Lis a bond.32. The compound of claim 27 , wherein Lis —C(═O)—.33. The compound of claim 27 , wherein Lis —S(═O)— or —S(═O)—.34. The compound of claim 27 , wherein Ring A is substituted or unsubstituted claim 27 , 4- to 7-membered claim 27 , monocyclic heterocyclyl claim 27 , ...

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Номер записи: 75
07-03-2019 дата публикации

COMBINATIONS FOR THE TREATMENT OF NEUROBLASTOMA

Номер: US20190070173A1
Автор: Anderson David Wesley, Brodeur Garrett M., Hornby Zachary Dolph, Iyer Radhika, Li Gang
Принадлежит: IGNYTA, INC.

Disclosed are methods of treating neuroblastoma in a cancer patient by administration of a Trk inhibitor in combination with one more chemotherapeutic agents. Also disclosed are pharmaceutical compositions comprising a Trk inhibitor and one or more chemotherapeutic agents. 1. A method for treating neuroblastoma in a patient , the method comprising administering to said patient a therapeutically effective amount of N-[5-(3 ,5-difluorobenzyl) -1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino) benzamide , or a pharmaceutically acceptable salt thereof , in combination with at least one topoisomerase I inhibitor and at least one alkylating agent , and wherein said neuroblastoma is tropomyosin-receptor-kinase positive prior to the administration of said N-[5-(3 ,5 -difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino) benzamide , or a pharmaceutically acceptable salt thereof , to said patient , and said N-[5-(3 ,5 -difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino) benzamide , or a pharmaceutically acceptable salt thereof , is administered to said patient at least once per day.220.-. (canceled)21. The method according to claim 1 , wherein said tropomyosin-receptor kinase is selected from TrkA claim 1 , TrkB claim 1 , and TrkC.22. The method according to claim 1 , wherein said tropomyosin-receptor kinase is TrkA.23. The method according to claim 1 , wherein said tropomyosin-receptor kinase is TrkB.24. The method according to claim 1 , wherein said tropomyosin-receptor kinase is TrkC.25. The method according to claim 1 , wherein said tropomyosin-receptor-kinase is at least two of TrkA claim 1 , TrkB claim 1 , and TrkC.26. The method according to claim 1 , wherein said topoisomerase I inhibitor is selected from irinotecan claim 1 , topotecan claim 1 , camptothecin and lamellarin D.27. The method according to claim 1 , wherein said alkylating agent is selected ...

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Номер записи: 76
15-03-2018 дата публикации

Sodium Channel Modulators

Номер: US20180072656A1
Автор: Jarrot Bevyn, Williams Spencer John
Принадлежит:

The present disclosure relates generally to compounds having activity as voltage-gated sodium channel blockers and their use in the field of therapeutic treatment, including the therapy or management of conditions associated with excessive, unwanted, inadequate or otherwise undesirable sodium ion passage through cellular membranes via voltage-gated sodium channels. In some embodiments, the disclosure relates to aryloxy-substituted amines for use as sodium channel blockers or modulators. Methods for their manufacture and compositions containing the compounds are also disclosed. 2. The compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein A is optionally substituted phenyl or optionally substituted 6-membered heteroaryl group.3. The compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein A is optionally substituted phenyl or optionally substituted 5-membered heteroaryl group.4. The compound according to or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein A is optionally 2 claim 1 ,6-dimethylphenyl.5. The compound according to or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein A is an optionally substituted pyridinyl claim 1 , pyridazinyl claim 1 , pyrimidinyl or pyrazinyl group.6. The compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein Land Lare independently optionally substituted methylene claim 1 , ethylene or propylene.7. The compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein Lis unsubstituted and Lis unsubstituted; or Lis unsubstituted and Lis substituted or; Lis substituted and Lis substituted; or Lis substituted and Lis unsubstituted.8. The compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein B is optionally substituted phenyl or optionally ...

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Номер записи: 77
15-03-2018 дата публикации

CONDENSED RING DERIVATIVE, AND PREPARATION METHOD, INTERMEDIATE, PHARMACEUTICAL COMPOSITION AND USE THEREOF

Номер: US20180072678A1
Автор: SUN Qingrui, WU Tianzhi, XU Zusheng, Zhang Nong
Принадлежит:

Disclosed are a condensed ring derivative, and a preparation method, an intermediate, a pharmaceutical composition and a use thereof. The condensed ring derivative of the present invention has a significant inhibitive effect on URAT1, which can effectively alleviate or treat hyperuricemia and other related diseases. 2. The condensed ring derivative having a structure of formula I claim 1 , the tautomer claim 1 , the mesomer claim 1 , the racemate claim 1 , the enantiomer claim 1 , the diastereoisomer claim 1 , or the pharmaceutically acceptable salt claim 1 , the metabolite claim 1 , the metabolic precursor or the pro-drug thereof according to claim 1 , wherein claim 1 ,M is H or a pharmaceutically acceptable cation;{'sup': 1', '2', '1', '2, 'each of Rand Ris independently H, D or an alkyl; or Rand R, together with the carbon atom attached form a cycloalkyl;'}{'sup': '3', 'Ris H, a halogen, an alkyl or an aryl;'}{'sup': '4', 'Ris H, a halogen, an alkyl, an aryl or a heteroaryl;'}{'sup': 5', '6, 'each of Rand Ris independently H, OH, a halogen or an alkyl;'}p is 1.14. A use of the condensed ring derivative having a structure of formula I claim 1 , the tautomer claim 1 , the mesomer claim 1 , the racemate claim 1 , the enantiomer claim 1 , the diastereoisomer claim 1 , or the pharmaceutically acceptable salt claim 1 , the metabolite claim 1 , the metabolic precursor or the pro-drug thereof according to at least one of - in manufacturing a medicament in preventing and/or treating hyperuricemia or the disease related to hyperuricemia.15. The use according to claim 14 , wherein claim 14 , the disease related to hyperuricemia is selected from the group consisting of gout claim 14 , hypertension claim 14 , diabetes claim 14 , hypertriglyceridemia claim 14 , metabolic syndrome claim 14 , coronary heart disease and kidney damage.16. A pharmaceutical composition claim 14 , which contains a pharmaceutically effective amount of the condensed ring derivative having a structure ...

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Номер записи: 78
16-03-2017 дата публикации

New Pyrazolyl-substituted Heteroaryls and their use as Medicaments

Номер: US20170073333A1
Автор: DAHMANN Georg, FANDRICK Daniel, GNAMM Christian, HOFFMANN Matthias, McCARTHY Clive, Scott John
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to new substituted heteroaryls of formula 1 2. The compound of formula 1 or of formula 1′ of claim 1 , whereinwherein A is either N or CH,{'sub': '2', 'wherein Y is either —O— or CH,'}{'sup': '3', 'sub': 1-6', '1-2', '3-6', '1-2', '3-6', '1-2', '3-6, 'wherein Ris a substituent in ortho- or in meta-position of the pyrazolyl-ring of formula 1 and is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, —C-fluoroalkyl, cyclopropyl, cyclobutyl, cyclopentyl, —C-alkylene-C-cyclopropyl, —C-alkylene-C-cyclobutyl, —C-alkylene-C-cyclopentyl, a five- or six-membered monocyclic heterocycle with 1 oxygen-atom, a 9- to 10-membered bicyclic heterocycle with 1 or 2 heteroatoms each independently selected from O, S or N,'}{'sup': '3', 'wherein Ris optionally substituted by one, two, three or four substituents each independently from each other selected from the group consisting of F, Cl, Br, methyl, ethyl, —CN'}{'sup': '2', 'sub': '3', 'wherein Ris selected from the group consisting of methyl, ethyl, isopropyl, —CF, F, Br, Cl,'}and the pharmaceutically acceptable salts of the aforementioned compounds.3. The compound of formula 1 or of formula 1′ of claim 1 , whereinwherein A is either N or CH,{'sub': '2', 'wherein Y is either —O— or —CH—,'}{'sup': '3', 'sub': 2', '2', '3', '2', '2', '3-6, 'wherein Ris a substituent in ortho- or in meta-position of the pyrazolyl-ring of formula 1 and is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, —(CH)—CF, —CH—CHF, cyclopropyl, cyclobutyl, cyclopentyl, -methylene-C-cyclopropyl, tetrahydrofuranyl, tetrahydropyranyl, hexahydrofuropyranyl,'}{'sup': '3', 'wherein Ris optionally substituted by one, two, three or four substituents each independently from each other selected from the group consisting of F, Cl, Br, methyl, ethyl, —CN'}{'sup': '2', 'wherein Ris selected from the group consisting of methyl and F,'}and the ...

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Номер записи: 79
18-03-2021 дата публикации

PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER

Номер: US20210078970A1
Автор: Chen Gang, Gu Jiamin, KONG Xianqi, Lu Jiasheng, SUN Chengyong, Zhang Qiguo
Принадлежит:

There are provided compounds of Formula I, and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, useful for inhibition or modulation of the activity of tyrosine kinases and treatment of disease states or conditions mediated by tyrosine kinases, including cancers. 3. The compound of claim 2 , wherein the PEG moiety is R—(OCHCH)— claim 2 , where n is 1 to 10 claim 2 , and Ris a hydrogen or a lower alkyl.4. The compound of claim 2 , wherein the ester-forming group is a lower alkyl or an aryl group.5. The compound of claim 2 , wherein the salt-forming moiety is a sodium claim 2 , a potassium claim 2 , a tetraethylammonium claim 2 , or a tetrabutylammonium.7. The compound of claim 6 , wherein the PEG moiety is R—(OCHCH)— claim 6 , where n is 1 to 10 claim 6 , and Ris a hydrogen or a lower alkyl.8. The compound of claim 6 , wherein the ester forming group is a lower alkyl or an aryl group.9. The compound of claim 6 , wherein the salt-forming moiety is a sodium claim 6 , a potassium claim 6 , a tetraethylammonium claim 6 , or a tetrabutylammonium.11. The compound of claim 1 , wherein the compound is a prodrug of axitinib.12. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.13. A method for the inhibition or modulation of the activity of a tyrosine kinase in a subject claim 1 , comprising administering to the subject an effective amount of the compound claim 1 , such that the tyrosine kinase is inhibited or modulated in the subject.14. The method of claim 13 , wherein the subject suffers from a tumor or a cancer.15. The method of claim 14 , wherein the tumor or the cancer is a solid tumor.16. The method of claim 14 , wherein the tumor or the cancer is breast cancer claim 14 , renal cell carcinoma claim 14 , or thyroid cancer.17. (canceled)18. The method of claim 13 , wherein the subject is a mammal.19. The method of claim 18 , wherein the mammal is a human.2026.-. (canceled)27. A ...

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Номер записи: 80
22-03-2018 дата публикации

AGENT FOR REDUCING VISCERAL FAT WEIGHT

Номер: US20180078530A1
Автор: Murakami Kentaro, Takizawa Toshiaki
Принадлежит: KOWA CO., LTD.

An FGF21 production promoting agent containing, as an active ingredient, a compound represented by the following formula (1): 2. The method of claim 1 , wherein the (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid or a salt thereof is administered in a divided dose from one to three times daily.3. The method of claim 1 , wherein the (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid or a salt thereof is administered in a daily dose of 0.1 to 100 mg.4. The method of claim 2 , wherein the (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid or a salt thereof is administered in a daily dose of 0.1 to 100 mg.5. The method of claim 2 , wherein the (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid or a salt thereof is administered 0.1 to 1 mg/day. This application is a continuation of U.S. application Ser. No. 13/393,164 filed Feb. 28, 2012, pending and incorporated herein by reference, which is a National Stage of PCT/JP10/066678 filed Sep. 27, 2010 and claims the benefit of JP 2009-222853 filed Sep. 28, 2009.The present invention relates to an agent for promoting production of FGF21 (hereinafter may be referred to as an “FGF21 production promoting agent”), an agent for reducing visceral fat weight (hereinafter may be referred to as a “visceral fat weight reducing agent”), and a preventive and/or therapeutic agent for obesity or metabolic syndrome, each of the agents containing, as an active ingredient, compound (1) which selectively activates α-type peroxisome proliferator-activated receptor (PPARα).PPAR is a receptor belonging to the nuclear receptor family. PPAR binds to specific sites (peroxisome proliferator response elements, PPREs) of a target gene, and positively or negatively regulates transcription of the gene. As has been known, this receptor has three subtypes (α, γ, and δ) (Non-Patent ...

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Номер записи: 81
23-03-2017 дата публикации

Sydnone derivatives for conjugation of compounds of interest

Номер: US20170081300A1
Автор: Alain Wagner, Frédéric Taran, Oleksandr Koniev, Sergii KOLODYCH
Принадлежит: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS, Commissariat a lEnergie Atomique et aux Energies Alternatives CEA, Universite De Strasbourg

The present invention relates to a process for the preparation of a first compound of interest C1 functionalized with a sydnone compound and to the corresponding functionalized C1 compound of interest. The present invention also relates to a process for the preparation of a conjugate of two compounds of interest C1 and C2 implying a sydnone compound and to the obtained conjugate. The present invention also relates to a process for preparing a compound of interest C2 comprising a strained alkyne moiety functionalized with a sydnone and to the corresponding functionalized compound of interest C2. It also relates to novel sydnone compounds substituted in position 4, which may be used in the above processes.

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Номер записи: 82
24-03-2016 дата публикации

DETECTION OF INDAZOLE SYNTHETIC CANNABINOIDS

Номер: US20160084859A1
Автор: Benchikh Elouard, Fitzgerald Peter, Lowry Phillip, Mcconnell Ivan
Принадлежит: Randox Laboratories Limited

Components for enabling immunodection of indazole synthetic cannabinoids are described including immunogens, haptens, antibodies, methods and kits. 2. The immunogen of claim 1 , wherein:{'sub': 'n', 'Y is -(A)-B-D-;'}A is a functional group or heteroatom enabling attachment of the crosslinking group to the indazole;{'sub': '1-10', 'B is a Csubstituted or unsubstituted alkylene moiety optionally incorporating an aryl, cycloalkyl and/or a heterocyclic moiety;'}D is a functional group or heteroatom enabling attachment of the crosslinking group to the antigenicity-conferring carrier material; andn=0 or 1.3. The immunogen of claim 2 , wherein:n=0; and{'sub': 2', '2', '2', '2, 'D is —C(O)—, —NH—, —C═, —C(O)—NH—, —S—, —C(O)—NH—, —C(O)—NH—CH(COOH)—CH—CH—S—, or —C(O)—NH—CH(COOH)—CH—CH—S-maleimide-.'}47.-. (canceled)10. The antibody of claim 8 , which has a cross-reactivity of 100% to AB-Pinaca Pentanoic acid and greater than 50% cross-reactivity to AB-Pinaca claim 8 , 1-(5-hydroxypentyl) AB-Pinaca claim 8 , 1-(4-hydroxypentyl) AB-Pinaca claim 8 , and 5-fluoropentyl AB-Pinaca.11. The antibody of claim 8 , which has a cross-reactivity of 100% to AB-Pinaca Pentanoic acid and greater than 75% cross-reactivity to 1-(5-hydroxypentyl) AB-Pinaca claim 8 , 1-(4-hydroxypentyl) AB-Pinaca claim 8 , and 5-fluoropentyl AB-Pinaca.12. The antibody of claim 8 , which has a cross-reactivity of 100% to AB-Pinaca Pentanoic acid and greater than 50% cross-reactivity to AB-Pinaca claim 8 , 1-(5-hydroxypentyl) AB-Pinaca claim 8 , 1-(4-hydroxypentyl) AB-Pinaca claim 8 , and 5-fluoropentyl AB-Pinaca and less than 50% to AB-Fubinaca.13. The antibody of claim 8 , which has an ICof less than about 20 ng/ml to AB-Pinaca claim 8 , 1-(5-hydroxypentyl) AB-Pinaca claim 8 , 5-fluoropentyl AB-Pinaca claim 8 , AB-Pinaca Pentanoic acid claim 8 , and AB-Fubinaca.1418.-. (canceled)20. The method of claim 19 , in which the compound of structure IIIb is one or more of AB-Pinaca claim 19 , 1-(5-hydroxypentyl) AB- ...

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Номер записи: 83
29-03-2018 дата публикации

Indazole Compounds for Use in Tendon and/or Ligament Injuries

Номер: US20180086716A1
Автор: BURSULAYA Badry, FISCH Andreas, Lajiness James Paul, MACHAUER Rainer, MALEKAR Swapnil, PETRASSI Hank Michael James, RAMAZANI Farshad, REMOND Anne-Catherine, ULLRICH Thomas, USSELMANN Peggy, VANGREVELINGHE Eric
Принадлежит:

The present invention provides a compound of formula (I) in free form or in pharmaceutically acceptable salt form 3. A compound according to in free form or in pharmaceutically acceptable salt form claim 1 , wherein{'sub': '1', 'Ris selected from methyl, chloro, fluoro and methoxy; and'}{'sub': '2', 'Ris selected from methyl and chloro.'}4. A compound according to in free form or in pharmaceutically acceptable salt form claim 1 , wherein{'sub': '3', 'Ris H; and'}{'sub': 4', '4', '6', '5, 'Ris a C-Ccycloalkyl substituted once or twice with R.'}5. A compound according to in free form or in pharmaceutically acceptable salt form claim 1 , wherein Ris independently selected from hydroxyl claim 1 , haloC-Calkyl claim 1 , halogen claim 1 , and C-Calkyl.6. A compound according to in free form or in pharmaceutically acceptable salt form claim 1 , wherein Rand Rtogether with the N atom to which they are attached form a 4- claim 1 , 5- or 6-membered heterocyclic ring substituted once claim 1 , twice or three times with R.7. A compound according to in free form or in pharmaceutically acceptable salt form claim 1 , wherein Ris independently selected from halogen claim 1 , hydroxyC-Calkyl claim 1 , hydroxyl claim 1 , and C-Calkyl.8. A compound according to in free form or in pharmaceutically acceptable salt form which is selected from5-(2-chloro-4-((3,3-dimethylazetidin-1-yl)sulfonyl)phenyl)-4-methyl-1H-indazol-3-amine;1-((4-(3-amino-4-methyl-1H-indazol-5-yl)-3-chlorophenyl)sulfonyl)pyrrolidin-3-ol;1-((4-(3-amino-4-methyl-1H-indazol-5-yl)-3-fluorophenyl)sulfonyl)pyrrolidin-3-ol;1-((4-(3-amino-4-methyl-1H-indazol-5-yl)-3-methylphenyl)sulfonyl)pyrrolidin-3-ol;1-((4-(3-amino-4-chloro-1H-indazol-5-yl)-3-fluorophenyl)sulfonyl)pyrrolidin-3-ol;1-((4-(3-amino-4-chloro-1H-indazol-5-yl)-3-methylphenyl)sulfonyl)pyrrolidin-3-ol;1-((4-(3-amino-4-chloro-1H-indazol-5-yl)-3-chlorophenyl)sulfonyl)pyrrolidin-3-ol;4-(3-amino-4-methyl-1H-indazol-5-yl)-N-(3-hydroxycyclobutyl)-3- ...

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Номер записи: 84
21-03-2019 дата публикации

ANALOGS OF FEXARAMINE AND METHODS OF MAKING AND USING

Номер: US20190084939A1
Автор: Atkins Annette, Baiga Thomas J., Downes Michael, Evans Ronald M., Fang Sungsoon, Keana John F.W., Liddle Christopher, Suh Jae Myoung, Yu Ruth T.
Принадлежит:

Novel compounds having a formula 1. A method of treating atherosclerosis in a subject , the method comprising administering to the subject an effective amount of an intestinally-selective , non-bile acid FXR agonist.3. The method of claim 2 , wherein Land Ltogether form a pi-bond.4. The method of claim 2 , wherein Ris deuterium.5. The method of claim 3 , wherein Ror Ror both are halogen.6. The method of claim 5 , wherein Ror Ror both are F.9. The method of claim 2 , wherein Rcomprises a nitrogen-containing heteroaryl ring.10. The method of claim 9 , wherein Ris selected from pyridine claim 9 , pyrazole claim 9 , pyrrole claim 9 , imidazole claim 9 , oxazole claim 9 , isoxazole claim 9 , thiazole claim 9 , isothiazole claim 9 , triazole claim 9 , pyrimidine claim 9 , pyrazine claim 9 , triazine claim 9 , benzopyrazole claim 9 , benzimidazole claim 9 , indole claim 9 , quinoline claim 9 , indazole claim 9 , purine claim 9 , quinoxaline claim 9 , or acridine.12. The method of claim 11 , wherein Z is N; R claim 11 , R claim 11 , Rand Rare all H; Ris methyl; or a combination thereof.14. The method of claim 13 , wherein Rand Rare both methyl.17. The method of claim 1 , wherein administering the FXR agonist comprises administering the FXR agonist to a gastrointestinal tract of the subject.18. The method of claim 1 , wherein the FXR agonist is administered orally.19. The method of claim 1 , wherein the FXR agonist is selected frommethyl (E)-3-(3-(N-(4-(1-methyl-1H-indazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl) acrylate;methyl (E)-3-(3-((1R,2S,4S)—N-(4-(1-methyl-1H-indazol-5-yl)benzyl)bicyclo[2.2.1]heptane-2-carboxamido)phenyl)acrylate;methyl (E)-3-(3-(1-methyl-N-(4-(1-methyl-1H-indazol-5-yl)benzyl)piperidine-4-carboxamido)phenyl)acrylate;methyl (E)-3-(5-(N-((1-methyl-1H-benzo[f]indazol-8-yl)methyl)cyclohexanecarboxamido)pyridin-3-yl) acrylate;methyl (E)-3-(3-fluoro-5-((1S,2R,4R)—N-((1-methyl-1H-benzo[f]indazol-8-yl)methyl)bicyclo[2.2.1]heptane-2-carboxamido)phenyl) ...

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Номер записи: 85
21-03-2019 дата публикации

PYRAZOLE DERIVATIVES USEFUL AS 5-LIPOXYGENASE ACTIVATING PROTEIN (FLAP) INHIBITORS

Номер: US20190084991A1
Автор: BRODDEFALK Johan Olof, EMTENÂS Hans Fredrik, GRANBERG Kenneth Lars, LEMURELL Malin Anita, PETTERSEN Daniel Tor, PLOWRIGHT Alleyn Thomas, ULANDER Lars Johan Andreas
Принадлежит: AstraZeneca AB

The present application relates to novel compounds of formula (I) 2. The compound of claim 1 , wherein Ris —H or —CH.3. The compound of claim 1 , wherein Rand Rare each independently —F or —H.4. The compound of claim 1 , wherein Ris —H.6. The compound of claim 1 , wherein Xis CH or CR claim 1 , wherein Ris as defined in .7. The compound of claim 1 , wherein Xis CRwherein Ris as defined in .8. The compound of claim 1 , wherein Ring A is an optionally and independently substituted pyrazole claim 1 , triazole claim 1 , oxazole claim 1 , thiazole claim 1 , oxadiazole or thiadiazole.10. The compound of claim 1 , wherein one of Xis CH claim 1 , Xis N and Xis NRand Ris as defined in .17. A compound according to claim 16 , which is (1R claim 16 ,2R)-2-[4-(3-Methyl-1H-pyrazol-5-yl)benzoyl]-N-(1-methyl-5-sulfamoyl-1H-pyrazol-4-yl)cyclohexanecarboxamide; or a pharmaceutically acceptable salt thereof.18. A pharmaceutical composition comprising a compound of Formula (I) claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , as claimed in claim 1 , and at least one pharmaceutically acceptable carrier claim 1 , diluent claim 1 , or excipient.1920-. (canceled)21. A method of treating diseases or conditions in which inhibition of FLAP is beneficial claim 1 , comprising administering to a patient in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof claim 1 , as claimed in . The present application relates to novel compounds that inhibit 5-lipoxygenase activating protein (FLAP) and therefore leukotriene production, to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), such as atherosclerosis, coronary artery disease (CAD), coronary heart disease (CHD), heart failure (HF), high risk coronary artery disease (HRCAD), and abdominal aortic aneurysms (AAA), to methods for their therapeutic use, to pharmaceutical compositions containing to them and to processes for ...

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Номер записи: 86
30-03-2017 дата публикации

BENZO-FUSED HETEROCYCLIC DERIVATIVES USEFUL AS AGONISTS OF GPR120

Номер: US20170088531A1
Автор: Subasinghe Nalin, Sui Zhihua
Принадлежит:

The present invention is directed to benzo-fused heterocyclic derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by GPR120. More particularly, the compounds of the present invention are agonists of GPR120, useful in the treatment of, such as for example, Type II diabetes mellitus. 10. A compound as in claim 1 , selected from the group consisting of3-{4-[(5-Chloro-2-ethyl-1-benzofuran-7-yl)methoxy]-2,3-dimethylphenyl}propanoic acid;3-(2,3-Dimethyl-4-{[2-methyl-5-(trifluoromethoxy)-1-benzofuran-7-yl]methoxy}phenyl)propanoic acid;3-(7-{[2-Methyl-5-(trifluoromethoxy)-1-benzofuran-7-yl]methoxy}-2,3-dihydro-1H-inden-4-yl)propanoic acid;3-{4-[(5-Chloro-2-methyl-1-benzofuran-7-yl)methoxy]-2,3-dimethylphenyl}propanoic acid;3-{4-[(5-Chloro-2,6-dimethyl-1-benzofuran-7-yl)methoxy]-2,3-dimethylphenyl}propanoic acid;3-(4-{[2-(2-Fluoroethenyl)-5-(trifluoromethoxy)-1-benzofuran-7-yl]methoxy}-2,3-dimethylphenyl)propanoic acid;3-{4-[(6-Chloro-2-methyl-1,3-benzothiazol-4-yl)methoxy]-2,3-dimethylphenyl}propanoic acid;and pharmaceutically acceptable salts thereof.11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of .12. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.13. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.14. A method of treating a disorder modulated by the GPR120 receptor claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of the compound of .15. The method of claim 14 , wherein the disorder modulated by the GPR120 receptor is selected from the group consisting of obesity claim 14 , obesity related disorders claim 14 , impaired oral glucose tolerance claim 14 , insulin resistance claim 14 , Type II diabetes mellitus claim 14 , metabolic syndrome claim 14 , metabolic syndrome X ...

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Номер записи: 87
29-03-2018 дата публикации

ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES

Номер: US20180090691A1
Автор: Brooks Jason, Chen Hsiao-Fan, Deng Jun, Djurovich Peter I., Morello Glenn, SZIGETHY Geza
Принадлежит: UNIVERSAL DISPLAY CORPORATION

Imidazophenanthridine ligands and metal complexes are provided. The compounds exhibit improved stability through a linking substitution that links a nitrogen bonded carbon of an imidizole ring to a carbon on the adjacent fused aryl ring. The compounds may be used in organic light emitting devices, particularly as emissive dopants, providing devices with improved efficiency, stability, and manufacturing. In particular, the compounds provided herein may be used in blue devices having high efficiency. 2. The compound of claim 1 , wherein the ligand Lis one of the ligands defined by Ldesignated using the formula A-R—R—R—R—R—R—R;{'sup': 'Z', 'wherein Z is an integer from 1 to 222 whereby Arepresents A1through A222;'}wherein j is an integer from 1 to 6; and k, l, m, n and o are integers from 1 to 5;wherein i=222((6((5((5((5((5(o−1)+n)−1)+m)−1)+l)−1)+k)−1)+j)−1)+Z.3. The compound of claim 1 , wherein the compound has a triplet excited state and wherein the linking group A stabilizes the bond between Nand Cfrom cleavage when the compound is in the triplet excited state.4. The compound of claim 1 , wherein the compound has a peak emissive wavelength less than 500 nm.5. (canceled)6. (canceled)8. The compound of claim 1 , wherein the metal is selected from the group consisting of Re claim 1 , Ru claim 1 , Os claim 1 , Rh claim 1 , Ir claim 1 , Pd claim 1 , Pt claim 1 , and Au.9. The compound of claim 1 , wherein the metal is selected from the group consisting of Ir and Pt.1112.-. (canceled)15. The compound of claim 1 , wherein the compound is (L)Ir.16. The compound of claim 10 , wherein the compound is (L)Ir(L)or (L)Ir(L).1922.-. (canceled)24. The OLED of claim 23 , wherein the organic layer is an emissive layer and the compound is an emissive dopant or a non-emissive dopant.25. The OLED of claim 23 , wherein the organic layer further comprises a host claim 23 , wherein the host comprises at least one selected from the group consisting of metal complex claim 23 , triphenylene ...

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Номер записи: 88
01-04-2021 дата публикации

BICYCLIC HETEROCYCLES AS FGFR INHIBITORS

Номер: US20210094935A1
Автор: Vechorkin Oleg, Yao Wenqing, Ye Hai Fen
Принадлежит:

The present invention relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR3 enzyme and are useful in the treatment of FGFR3-associated diseases such as cancer. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cyis 5 or 6-membered heteroaryl optionally substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents independently selected from R.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cyis 5-membered heteroaryl optionally substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents independently selected from R.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cyis pyrazolyl optionally substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents independently selected from R.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cyis 6-membered heteroaryl optionally substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents independently selected from R.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cyis pyridinyl optionally substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents independently selected from R.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cyis phenyl optionally substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents independently selected from R.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Cyis selected from pyrazolyl claim 1 , pyridinyl claim 1 , and phenyl; each of which is optionally substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substituents independently selected from R.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently selected from Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl claim 1 , 4-10 ...

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Номер записи: 89
28-03-2019 дата публикации

MEDICAMENT FOR LIVER REGENERATION AND FOR TREATMENT OF LIVER FAILURE

Номер: US20190091265A1
Автор: Wuestefeld Torsten, Zender Lars
Принадлежит:

The present invention relates to the use of a compound which inhibits the activity of MKK4 as a medicament for the treatment of a patient suffering from an impaired liver function, to the use of a compound as a medicament for the treatment of liver failure, including acute/fulminant or chronic liver failure and/or for increasing the regeneration of liver tissue in a patient. 1. A method of treatment of liver failure and/or for the treatment of impaired liver function and/or for the protection of hepatocytes against apoptosis and/or for the regeneration of hepatocytes , the method comprising a step of administering to a patient in need of treatment a compound , which is an inhibitor of the activity of MKK4 , wherein said MKK4 is encoded by mRNA with SEQ ID NO: 1204 , wherein the compound is not SP600125 , myricitine , PD98059 , genistein , or ZM 336372.3. The method according to claim 1 , wherein the compound is formulated as liposomes or lipid nanoparticles.4. The method according to claim 1 , wherein the patient is a human patient.5. A cultivated hepatocyte for treatment of liver failure and/or for treatment of impaired liver function and/or for blood purification claim 1 , characterized in that the hepatocyte contains a compound which is an inhibitor of the activity of MKK4 claim 1 , wherein said MKK4 encoded by SEQ ID NO: 1204 and the compound is not SP600125 claim 1 , myricitine claim 1 , PD98059 claim 1 , genistein claim 1 , or ZM 336372.6. A medicament comprising the cultivated hepatocyte of .7. The cultivated hepatocyte of claim 5 , wherein the hepatocyte is arranged in a vessel having an entry port for entry of blood of a patient and an exit port for recirculating the blood to the patient.8. The cultivated hepatocyte of claim 5 , wherein the compound is one or more of the compounds of . This application is a continuation of U.S. patent application Ser. No. 14/875,879 filed Oct. 6, 2015, pending, which is a continuation of U.S. patent application Ser. No. 14/ ...

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Номер записи: 90
12-05-2022 дата публикации

BENZOINDAZOLONE COMPOUND AND INTERMEDIATE THEREOF

Номер: US20220144780A1
Автор: KO In Seok, LEE Eun Ju, LEE Whee Seong
Принадлежит: LMITO THERAPEUTICS INC.

Provided are a benzoindazolone compound, or a pharmaceutically acceptable salt, hydrate, solvate, enantiomer, diasteromer, tautomer or prodrug thereof; and an intermediate thereof, wherein the compound is used as a substrate for NQO1 to facilitate a redox reaction of NQO1, and thus is expected to be developable as a medicine for preventing or treating inflammatory diseases. 2. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , enantiomer claim 1 , diasteromer claim 1 , tautomer or prodrug thereof claim 1 , wherein at least one of R claim 1 , Rand Ris Calkoxy.3. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , enantiomer claim 1 , diasteromer claim 1 , tautomer or prodrug thereof claim 1 , wherein at least one of bonds between Rand X claim 1 , Rand X claim 1 , and Rand Xis C═O.4. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , enantiomer claim 1 , diasteromer claim 1 , tautomer or prodrug thereof claim 1 , wherein at least two of are double bonds.5. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , enantiomer claim 1 , diasteromer claim 1 , tautomer or prodrug thereof claim 1 , wherein Xand Xare C claim 1 , and Xand Xare N.6. The compound according to claim 5 , or a pharmaceutically acceptable salt claim 5 , hydrate claim 5 , solvate claim 5 , enantiomer claim 5 , diasteromer claim 5 , tautomer or prodrug thereof claim 5 , wherein Ris Calkoxy.7. The compound according to claim 5 , or a pharmaceutically acceptable salt claim 5 , hydrate claim 5 , solvate claim 5 , enantiomer claim 5 , diasteromer claim 5 , tautomer or prodrug thereof claim 5 , wherein the bond between Rand Xis C═O.8. The compound according to claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate ...

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Номер записи: 91
12-05-2022 дата публикации

THERAPEUTIC INDAZOLES

Номер: US20220144781A1
Автор: ALLAND David, AWASTHI Divya, CAPODAGLI Glenn, Ekins Sean, FREUNDLICH Joel S., Kumar Pradeep, NEIDITCH Matthew B.
Принадлежит: Rutgers, The State University of New Jersey

The invention provides compounds of formula I: 3. The method of claim 1 , wherein Ris H claim 1 , methyl claim 1 , or CD3.4. The method of claim 1 , wherein Ris H or methyl.5. The method of claim 1 , Ris H and Ris —N(R)SOR.6. The method of claim 1 , Ris —N(R)SORand Ris H.7. The method of claim 1 , Ris H and Ris —N(R)C(═S)N(R)R.8. The method of claim 1 , wherein Ris —N(R)C(═S)N(R)Rand Ris H.9. The method of claim 1 , wherein:{'sup': '1', 'sub': 1', '4, 'Ris H, or (C-C)alkyl;'}{'sup': '2', 'sub': 1', '4, 'Ris H, (C-C)alkyl, or halo;'}{'sup': 3', '4', 'a', 'c', 'a', 'a', 'c', '3', 'a', 'a', 'a', 'c', '4, 'sub': 2', '2, 'Ris H and Ris —N(R)SORor —N(R)C(═S)N(R)R; or Ris —N(R)SOC or —N(R)C(═S)N(R)Rand Ris H;'}{'sup': 'a', 'sub': 1', '4, 'each Ris independently H or (C-C)alkyl; and'}{'sup': 'c', 'sub': 3', '6', '2', '6', '3', '6', '2', '6, 'Ris (C-C)cycloalkyl, or (C-C)alkyl, wherein any (C-C)cycloalkyl and (C-C)alkyl is optionally substituted with one or more groups independently selected from the group consisting of halo, and cyano.'}10. The method of claim 1 , wherein:{'sup': '1', 'Ris H;'}{'sup': '2', 'sub': 1', '4, 'Ris H, halo, or (C-C)alkyl that is optionally substituted with one or more halo;'}{'sup': 3', '4', 'a', 'c, 'sub': '2', 'Ris H and Ris —N(R)SOR,'}{'sup': '5', 'sub': 1', '4, 'Ris H, (C-C)alkyl, or halo;'}{'sup': 'a', 'sub': 1', '4, 'each Ris independently H or (C-C)alkyl; and'}{'sup': 'c', 'sub': 3', '6', '2', '6', '3', '6', '2', '6', '3', '6', '1', '4, 'Ris (C-C)cycloalkyl, or (C-C)alkyl, wherein any (C-C)cycloalkyl and (C-C)alkyl is optionally substituted with one or more groups independently selected from the group consisting of halo, (C-C)cycloalkyl, phenyl, (C-C)alkoxy, trifluoromethyl, and cyano.'}12. The method of claim 10 , wherein Ris H or methyl.13. The method of claim 10 , wherein{'sup': '1', 'Ris H;'}{'sup': '2', 'sub': 1', '4, 'Ris H, (C-C)alkyl, or halo;'}{'sup': 3', '4', 'a', 'c, 'sub': '2', 'Ris H and Ris —N(R)SOR;'}{'sup': 'a', 'sub': 1', ...

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Номер записи: 92
06-04-2017 дата публикации

Selective androgen receptor degrader (sard) ligands and methods of use thereof

Номер: US20170095446A1
Автор: Charles B. Duke, Christopher C. Coss, Dong-Jin Hwang, Duane D. Miller, James T. Dalton, Jayaprakash Pagadala, Ramesh Narayanan, Thamarai Ponnusamy, Yali He
Принадлежит: GTx Inc, UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION

This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

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Номер записи: 93
06-04-2017 дата публикации

ALKYNYL INDAZOLE DERIVATIVE AND USE THEREOF

Номер: US20170096400A1
Автор: MACHIDA Mamiko, MACHIDA Shinnosuke, MIYABE Tomoyo, NAKAJIMA Takeshi, Takeda Norihiko
Принадлежит: SENJU PHARMACEUTICAL CO., LTD.

The main object of the present invention is to provide a novel compound which has a VEGF receptor tyrosine kinase inhibitory activity and is useful as an active ingredient for the treatment of diseases accompanying angiogenesis or edema, for example, age-related macular degeneration or the like. 2. The alkynyl indazole derivative according to claim 1 , or the pharmaceutically acceptable salt thereof claim 1 , wherein X and Y are simultaneously CH.3. The alkynyl indazole derivative according to or the pharmaceutically acceptable salt thereof claim 1 , wherein Z is bound in the para-position.5. A medicine characterized by containing the alkynyl indazole derivative according to or the pharmaceutically acceptable salt thereof.6. The medicine according to claim 5 , which is a vascular endothelial cell growth factor (VEGF) receptor tyrosine kinase inhibitor.7. The medicine according to which is used for treatment or prevention of a retinal disease accompanying angiogenesis or edema.8. The medicine according to claim 7 , wherein the retinal disease accompanying angiogenesis or edema is age-related macular degeneration claim 7 , macular edema claim 7 , diabetic retinopathy claim 7 , retinopathy of prematurity claim 7 , retinal vein occlusion claim 7 , secondary cataract claim 7 , myopic choroidal neovascularization claim 7 , or glaucoma.9. A method for treating a disease or condition accompanying angiogenesis or edema in a mammal claim 1 , the method comprising the step of administering the alkynyl indazole derivative according to claim 1 , or the pharmaceutically acceptable salt thereof claim 1 , to the mammal.10. The method according to claim 9 , wherein the disease or condition accompanying angiogenesis or edema to be treated is a retinal disease accompanying angiogenesis or edema.11. The method according to claim 10 , wherein the retinal disease accompanying angiogenesis or edema is age-related macular degeneration claim 10 , macular edema claim 10 , diabetic ...

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Номер записи: 94
06-04-2017 дата публикации

PYRAZOLE-SUBSTITUTED ARYLAMIDES AS P2X3 AND P2X2/3 ANTAGONISTS

Номер: US20170096416A1
Автор: Chen Li, Dillon Michael Patrick, Feng Lichun, Hawley Ronald Charles, YANG Minmin
Принадлежит: Roche Palo Alto LLC

Compounds of the formula I: 2. The compound of claim 1 , wherein Ris 1H-pyrazol-1-yl substituted once with Calkyl or halo-Calkyl.3. The compound of claim 1 , wherein Ris phenyl substituted at the 4-position with methyl or halo and optionally substituted at the 2- and 6-positions with halo.4. The compound of claim 1 , wherein Ris 4-methyl-phenyl claim 1 , 2-fluoro-4-methyl-phenyl claim 1 , 2-chloro-4-fluoro-phenyl claim 1 , 4-chloro-2-fluoro-phenyl claim 1 , 2 claim 1 ,4-dichloro-phenyl claim 1 , 2 claim 1 ,4-difluoro-phenyl claim 1 , or 2-chloro-4-methyl-phenyl.5. The compound of claim 1 , wherein Ris pyridin 2-yl substituted with methyl or halo at the 5-position and optionally substituted with halo at the 3-position.6. The compound of claim 1 , wherein Ris 5-methyl-pyridin-2-yl claim 1 , 5-chloro-pyridin-2-yl claim 1 , 5-fluoro-pyridin-2-yl claim 1 , 5-methyl-3-fluoro-pyridin-2-yl claim 1 , 5-methyl-3-chloro-pyridin-2-yl claim 1 , 3 claim 1 ,5-difluoro-pyridin-2-yl or 3 claim 1 ,5-dichloro-ppyridin-2-yl.7. The compound of claim 1 , wherein R claim 1 , Rand Rare hydrogen.8. The compound of claim 1 , wherein Ris hydrogen.9. The compound of claim 1 , wherein Ris hydrogen.10. The compound of claim 1 , wherein Ris methyl.11. The compound of claim 1 , wherein Rand Rtogether with the atom to which they are attached form a Ccarbocyclic ring that is optionally substituted with hydroxy.12. The compound of claim 1 , wherein Ris: Calkyl; Calkyloxy-Calkyl; hydroxy-Calkyl; Calkylsulfanyl-Calkyl; Calkylsulfonyl-Calkyl; amino-Calkyl; N—Calkyl-amino-Calkyl; N claim 1 ,N-di-Calkyl-amino-Calkyl; Ccycloalkyl; optionally substituted phenyl; heteroaryl claim 1 , or heterocyclyl-Calkyl.13. The compound of claim 1 , wherein Ris: Calkyloxy-Calkyl; hydroxy-Calkyl; heteroaryl claim 1 , or heterocyclyl-Calkyl.14. The compound of claim 1 , wherein Ris: is hydroxymethyl claim 1 , methoxymethyl claim 1 , pyrazin-2-yl claim 1 , 5-methyl-pyrazin-2-yl claim 1 , 6-methyl-pyridazin-3-yl claim 1 , or ...

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Номер записи: 95
12-04-2018 дата публикации

COMPOUNDS AND METHODS FOR IDO AND TDO MODULATION AND INDICATIONS THEREFOR

Номер: US20180099939A1
Автор: Albers Aaron, BUELL JOHN, PHAM PHUONGLY, Powers Hannah, Spevak Wayne, Wu Guoxian, Zhang Jiazhong
Принадлежит:

Disclosed are compounds of Formula I(a): 9. The compound according to wherein Ris H; Ris Cl; and Ris H claim 1 , Cl or F.14. The compounds according to claim 1 , wherein Zis:{'sub': 3', '2', '3', '3', '3', '2', '3', '2', '2', '3', '3', '2', '3', '3', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '2', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2', '3', '3', '2', '3', '3', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2', '3', '3', '2', '3', '3', '2', '3', '2', '3', '3', '3', '3, 'sup': '5', '—C(O)—O—CH, —C(O)—O—CHCH, C(O)—O—C(CH), —C(O)—O—CHCF, —C(O)—O—(CH)CH, —C(O)—O—CH(CH), —C(O)—O—C(CH), —C(O)—O—CHCH(CH), —C(O)—O-cyclopropyl, —C(O)—O-cyclobutyl, —C(O)—O-cyclopentyl, —C(O)—O-cyclohexyl, —C(O)—N(H)—SO—CH, —C(O)—N(H)—SO—CHCF, —C(O)—N(H)—SO—CHCH, —C(O)—N(H)—SO—(CH)CH, —C(O)—N(H)—SO—CH(CH), —C(O)—N(H)—SO—C(CH), —C(O)—N(H)—SO—CHCH(CH), —C(O)—N(H)—SO-cyclopropyl, —C(O)—N(H)—SO-cyclobutyl, —C(O)—N(H)—SO-cyclopentyl, —C(O)—N(H)—SO-cyclohexyl, —C(O)—N(H)—SO-phenyl, —C(O)—N(H)—SO-tetrahydro-2H-pyran, —C(O)—N(H)—SO-tetrahydro-2H-thiopyran, —C(O)—N(H)—SO-piperidinyl, —C(O)—N(H)—SO-piperazinyl, —C(O)—N(H)—SO-pyridyl, —C(O)—N(H)—SO-isoxazolyl, —C(O)—N(H)—SO-thiophenyl, —SO—CH, —SO—CHCH, —SO—CHCF, —SO—(CH)—CH, —SO—CH(CH), —SO—CHCH(CH), —SO-cyclopropyl, —SO-cyclobutyl, —SO-cyclopentyl, —SO-cyclohexyl, —SO-phenyl, —SO-tetrahydro-2H-pyran, —SO-tetrahydro-2H-thiopyran, —SO-pyridyl, —SO-isoxazole, —SO-thiophene, —C(O)—CH—OH, —C(O)(CH)—OH, —C(O)CH—C(CH)—OH, —CH(phenyl), —CH(cycloalkyl)—SO—N(CH), —C(O)CH, —C(O)CHCH—C(O)CHCF, —C(O)(CH)CH, —C(O)CH(CH), —C(O)C(CH), —C(O)CHCH(CH), —C(O)-cyclopropyl, —C(O)cyclobutyl, C(O)cyclopentyl, —C(O)cyclohexyl, —C(O)phenyl, —C(O) ...

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Номер записи: 96
08-04-2021 дата публикации

PREPARATION OF PYRAZOLO[3,4-B]PYRIDINES AS ANTIMALARIALS

Номер: US20210101901A1
Автор: Eagon Scott Charles, Guy Rodney Kiplin, Hammill Jared T.
Принадлежит:

The present invention relates to pyrazolo[3,4-b]pyridine compounds. The present invention further relates to methods for inhibiting comprising contacting with pyrazolo[3,4-b]pyridine compounds described herein. Also described herein are methods of treating malaria comprising administering pyrazolo[3,4-b]pyridine compounds to a subject in need thereof. 10PlasmodiumPlasmodium. A method for inhibiting the growth of comprising administering to cells infected with the compound of .11PlasmodiumPlasmodium falciparum.. The method of claim 10 , wherein the is12Plasmodium. The method of claim 10 , wherein the is drug resistant.13Plasmodium. The method of claim 12 , wherein the is atovaquone-resistant.14. The method of claim 10 , wherein the cells are in a subject.15. The method of claim 14 , wherein the subject is a human. This application claims priority from U.S. Provisional Patent Application No. 62/910,882 filed on Oct. 4, 2019 the entire disclosure of which is incorporated herein by this reference.The present invention relates to pyrazolo[3,4-b]pyridines as anti-malarial compounds and methods using the same.Malaria continues to remain one of the most deadly infectious diseases on the planet. The WHO reported more than 200 million cases 2017 with nearly 435,000 associated deaths, primarily in young children and pregnant women. Despite concerted efforts to combat the spread of Malaria, it continues to have a devastating effect in parts of Asia and Africa. The latest WHO summary, in fact, notes that “no significant progress in reducing global malaria cases was made” from 2015-2017.Malaria in humans is caused by hematoprotozoan parasites of the genus , with accounting for the vast majority of fatalities. The parasite has a complex life cycle that includes both a liver and erythrocytic stage, significantly increasing the challenge associated with combating infection. While a number of efforts have been made to combat the disease via vaccines and vector control, small-molecule ...

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Номер записи: 97
13-04-2017 дата публикации

PROCESS FOR THE PREPARATION OF (E)-3-(4-((E)-2-(2-CHLORO-4-FLUOROPHENYL)-1-(1H-INDAZOL-5-YL)BUT-1-EN-1-YL)PHENYL)ACRYLIC ACID

Номер: US20170101380A1
Автор: Bachmann Stephan, Fantasia Serena Maria, Gosselin Francis, Han Chong, Hildbrand Stefan, Humphries Theresa, Jenny Christian, LIM Ngiap-Kie, McClory Andrew, Moessner Christian, Rege Pankaj, Savage Scott, Zhang Haiming
Принадлежит: Genentech, Inc.

Processes are described for the preparation of estrogen receptor modulating compound, (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid I: 3. The process of wherein the palladium catalyst is selected from PdCl(PPh) claim 2 , Pd(t-Bu) claim 2 , PdCldppf CHCl claim 2 , Pd(PPh) claim 2 , Pd(OAc)/PPh claim 2 , ClPd[(P(Et)] claim 2 , Pd(DIPHOS) claim 2 , ClPd(Bipy) claim 2 , [PdCl(PhPCHPPh)] claim 2 , ClPd[P(o-tol)] claim 2 , Pd(dba)/P(o-tol) claim 2 , Pd(dba)/P(2-furyl) claim 2 , ClPd[P(2-furyl)] claim 2 , ClPd(PMePh) claim 2 , ClPd[P(4-F-Ph)] claim 2 , ClPd[P(CF)] claim 2 , ClPd[P(2-COOH-Ph)(Ph)] claim 2 , ClPd[P(4-COOH-Ph)(Ph)] claim 2 , and encapsulated catalysts Pd EnCat™ 30 claim 2 , Pd EnCat™ TPP30 claim 2 , and Pd(II)EnCat™ BINAP30.4. The process of wherein palladium is removed from IV with a solid adsorbent palladium scavenger.5. The process of wherein the solid adsorbent palladium scavenger is selected from silica gel claim 4 , controlled-pore glass claim 4 , and low cross-linked polystyrene.8. The process of further comprising forming the NMG salt of I with N-methyl-D-glucamine.11. The process of wherein the enolization reagent is selected from para-toluenesulfonic anhydride claim 10 , para-toluenesulfonyl chloride claim 10 , trifluoromethanesulfonic anhydride claim 10 , methanesulfonic anhydride claim 10 , methanesulfonyl chloride and diphenyl phosphoryl chloride.13. The process of wherein the derivatizing reagent is selected from pivaloyl chloride claim 12 , pivaloyl anhydride claim 12 , di-tert-butyl dicarbonate claim 12 , isopropyl carbonate claim 12 , methyl carbonate claim 12 , N claim 12 ,N-dimethyl carbamoyl chloride claim 12 , diphenylphosphoryl chloride claim 12 , isobutyl carbonate claim 12 , acetic anhydride claim 12 , trifluoroacetic anhydride claim 12 , trifluoroacetyl bis(2-oxo-3-oxazolidinyl)phosphoryl chloride claim 12 , and diethylphosphoryl chloride. This non-provisional application filed under 37 ...

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Номер записи: 98
13-04-2017 дата публикации

HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF

Номер: US20170101402A1
Автор: Allen Daniel R., Breccia Perla, Bürli Roland W., Dominguez Celia, Haughan Alan F., Hughes Samantha J., Jarvis Rebeca E., Luckhurst Christopher A., Muñoz-Sanjuán Ignacio, Penrose Stephen D., Raphy Gilles, Saville-Stones Elizabeth A., Stott Andrew J., Vater Huw D., Wall Michael, Wishart Grant
Принадлежит:

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, or pharmaceutically acceptable salts thereof, compositions thereof, and methods of their use. The condition or disorder mediated by HDAC comprises a neurodegenerative pathology. Accordingly, also provided is a method of treating a neurodegenerative pathology mediated by HDAC in a subject in need of such a treatment, comprising administering to the subject a therapeutically effective amount of at least one compound, or pharmaceutically acceptable salt thereof, described herein. 3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris chosen from phenyl optionally substituted with one or two substituents independently chosen from lower alkyl claim 2 , lower haloalkyl claim 2 , lower alkoxy claim 2 , lower haloalkoxy claim 2 , and halo.4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris chosen from phenyl claim 3 , 2-methylphenyl claim 3 , 3-methylphenyl claim 3 , 4-methylphenyl claim 3 , 2-fluorophenyl claim 3 , 3-fluorophenyl claim 3 , 4-fluorophenyl claim 3 , 2-chlorophenyl claim 3 , 3-chlorophenyl claim 3 , 4-chlorophenyl claim 3 , 3-chloro-2-fluorophenyl claim 3 , 2 claim 3 ,6-difluorophenyl claim 3 , 2 claim 3 ,5-dimethylphenyl claim 3 , 2 claim 3 ,6-dimethylphenyl claim 3 , 2-chloro-6-fluorophenyl claim 3 , 2-fluoro-6-methylphenyl claim 3 , 2 claim 3 ,4-difluorophenyl claim 3 , 4-(difluoromethoxy)phenyl claim 3 , and 3-fluoro-2-methylphenyl.5. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris chosen from pyridin-2-yl claim 2 , pyridin-4-yl claim 2 , and pyrazin-2-yl claim 2 , each of which is optionally substituted with one or two substituents independently chosen from lower alkyl and halo.6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris chosen from 5-fluoropyridin-2-yl claim 5 , pyrazin-2-yl claim 5 , and 3- ...

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Номер записи: 99
04-04-2019 дата публикации

Medicament for liver regeneration and for treatment of liver failure

Номер: US20190099453A1
Автор: Lars Zender, Torsten Wuestefeld
Принадлежит: Helmholtz Zentrum fuer Infektionsforschung HZI GmbH, MEDIZINISCHE HOCHSCHULE HANNOVER

The present invention relates to the use of a compound which inhibits the activity of MKK4 as a medicament for the treatment of a patient suffering from an impaired liver function, to the use of a compound as a medicament for the treatment of liver failure, including acute/fulminant or chronic liver failure and/or for increasing the regeneration of liver tissue in a patient.

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Номер записи: 100

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