- JNK INHIBITOR, PHARMACEUTICAL COMPOSITION THEREOF AND USE THEREOF
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Provided are a compound shown in formula (I) below, and racemates, stereoisomers, tautomers, isotopic markers, solvates, polymorphs and oxynitrides of the compound, or a pharmaceutically acceptable salt thereof, wherein same can be used as JNK inhibitors. Also provided are a method for preparing the compound shown in formula (I), a pharmaceutical composition comprising the compound shown in formula (I), and the use of the compound shown in formula (I) for preparing drugs, wherein the drugs are used for treating diseases which can be treated by inhibiting JNK activity.
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- NOVEL APOPTOSIS SIGNAL-REGULATING KINASE 1 INHIBITORS
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The present invention relates to inhibitors of apoptosis signal-regulating kinase 1 ("ASK1"), a process for synthesis of the compounds of the present invention, composition comprising the compounds and use of the compounds for inhibition of ASK1.
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- Discovery of 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1 H)-one (BMS-903452), an antidiabetic clinical candidate targeting GPR119
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G-protein-coupled receptor 119 (GPR119) is expressed predominantly in pancreatic β-cells and in enteroendocrine cells in the gastrointestinal tract. GPR119 agonists have been shown to stimulate glucose-dependent insulin release by direct action in the pancreas and to promote secretion of the incretin GLP-1 by action in the gastrointestinal tract. This dual mechanism of action has generated significant interest in the discovery of small molecule GPR119 agonists as a potential new treatment for type 2 diabetes. Herein, we describe the discovery and optimization of a new class of pyridone containing GPR119 agonists. The potent and selective BMS-903452 (42) was efficacious in both acute and chronic in vivo rodent models of diabetes. Dosing of 42 in a single ascending dose study in normal healthy humans showed a dose dependent increase in exposure and a trend toward increased total GLP-1 plasma levels.
- Wacker, Dean A.,Wang, Ying,Broekema, Matthias,Rossi, Karen,Oconnor, Steven,Hong, Zhenqiu,Wu, Ginger,Malmstrom, Sarah E.,Hung, Chen-Pin,Lamarre, Linda,Chimalakonda, Anjaneya,Zhang, Lisa,Xin, Li,Cai, Hong,Chu, Cuixia,Boehm, Stephanie,Zalaznick, Jacob,Ponticiello, Randolph,Sereda, Larisa,Han, Song-Ping,Zebo, Rachel,Zinker, Bradley,Luk, Chiuwa Emily,Wong, Richard,Everlof, Gerry,Li, Yi-Xin,Wu, Chunyu K.,Lee, Michelle,Griffen, Steven,Miller, Keith J.,Krupinski, John,Robl, Jeffrey A.
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supporting information
p. 7499 - 7508
(2014/12/11)
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- PYRIDONE GPR119 G PROTEIN-COUPLED RECEPTOR AGONISTS
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Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR 119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.
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Page/Page column 115-116
(2009/02/11)
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- QUINOXALINE DERIVATIVES AS INHIBITORS OF THE TYROSINE KINASE ACTIVITY OF JANUS KINASES
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The present invention relates to quinoxaline compound of the formula (I): wherein R1 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R7; R2 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R8; R3, R4, R5 and R6 are each independently hydrogen or R9; and R7, R8 and R9 are each independently selected from organic and inorganic substituents, their use in therapy of diseases, in particular diseases mediated by the tyrosine kinase activity of Janus kinases, including JAK-2 and JAK-3 kinases
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Page/Page column 53
(2009/01/24)
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- INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME
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The present invention provides compounds of formula (4), and their pharmaceutically acceptable salts and solvates, which are useful as inhibitors of the Hepatitis C virus (HCV) polymerase enzyme and are also useful for the treatment of HCV infections in HCV-infected mammals. The present invention also provides pharmaceutical compositions comprising compounds of formula (4), their pharmaceutically acceptable salts and solvates. Furthermore, the present invention provides intermediate compounds and methods useful in the preparation of compounds of formula (4).
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Page/Page column 148
(2008/06/13)
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- SELECTIVE ESTROGEN RECEPTOR MODULATORS CONTAINING A PHENYLSULFONYL GROUP
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The present invention relates to a selective estrogen receptor modulator of formula I or a pharmaceutical acid addition salt thereof; useful, e.g., for treating endometriosis and/or uterine leiomyoma/leiomyomata.
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Page/Page column 22-23
(2008/06/13)
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- Non-nucleoside reverse transcriptase inhibitors
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This invention relates to novel pyridazinone derivatives of formula I wherein R1-R4, R7, R8 and X1 are as defined in the summary and pharmaceutically acceptable salts and solvates thereof, methods to inhibit or modulate Human Immunodeficiency Virus (HIV) reverse transcriptase with compounds of formula I, pharmaceutical compositions containing of formula I admixed with at least one solvent, carrier or excipient and processes to prepare compounds of formula I. The compounds are useful for treating disorders in which HIV and genetically related viruses are implicated
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Page/Page column 91
(2010/02/08)
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- SUBSTITUTED ARYLCYCLOPROPYLACETAMIDES AS GLUCOKINASE ACTIVATORS
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According to the present invention there is provided a compounds of formula (I): and pharmaceutically acceptable salts thereof.
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