- Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases
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RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into
- Harris, Philip A.,Berger, Scott B.,Jeong, Jae U.,Nagilla, Rakesh,Bandyopadhyay, Deepak,Campobasso, Nino,Capriotti, Carol A.,Cox, Julie A.,Dare, Lauren,Dong, Xiaoyang,Eidam, Patrick M.,Finger, Joshua N.,Hoffman, Sandra J.,Kang, James,Kasparcova, Viera,King, Bryan W.,Lehr, Ruth,Lan, Yunfeng,Leister, Lara K.,Lich, John D.,MacDonald, Thomas T.,Miller, Nathan A.,Ouellette, Michael T.,Pao, Christina S.,Rahman, Attiq,Reilly, Michael A.,Rendina, Alan R.,Rivera, Elizabeth J.,Schaeffer, Michelle C.,Sehon, Clark A.,Singhaus, Robert R.,Sun, Helen H.,Swift, Barbara A.,Totoritis, Rachel D.,Vossenk?mper, Anna,Ward, Paris,Wisnoski, David D.,Zhang, Daohua,Marquis, Robert W.,Gough, Peter J.,Bertin, John
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- HETEROCYCLIC AMIDES AS KINASE INHIBITORS
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Disclosed are compounds having the formula (I) wherein X, Y, Z1, Z2, Z3, Z4, R5, RA, m, A. L, and B are as defined herein, and methods of making and using the same.
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Page/Page column 72
(2014/09/03)
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- Design, synthesis, and biological evaluation of 1,5-benzothiazepine-4-one derivatives targeting factor VIIa/tissue factor
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The 1,5-benzothiazepine-4-one scaffold was earlier shown to provide efficient protease inhibitors. In this contribution, we describe its use in the design of factor VIIa/tissue factor inhibitors. A series containing a scaffold non-substituted on its aryl part led to compound 20 with an IC50 of 2.16 μM. Following molecular modelling studies of this compound, a second series was prepared, which necessitated the synthesis of protected 7- or 8-substituted 1,5-benzothiazepine-4-one derivatives.
- Ayral, Erwan,Gloanec, Philippe,Berge, Gilbert,de Nanteuil, Guillaume,Mennecier, Philippe,Rupin, Alain,Verbeuren, Tony J.,Fulcrand, Pierre,Martinez, Jean,Hernandez, Jean-Francois
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supporting information; scheme or table
p. 1386 - 1391
(2009/10/15)
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- S-Aryl cysteine S,S-dioxides as inhibitors of mammalian kynureninase
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A series of 2-amino-S-aryl cysteine S,S-dioxides have been synthesised and shown to inhibit kynureninase an important enzyme in the biosynthesis of the known excitotoxic moiety quinolinic acid. The most potent of these, 2-amino-5-methyl-S-phenyl cysteine S,S-dioxide 6d, inhibits interferon-γ induced synthesis of quinolinic acid in human macrophages.
- Drysdale, Martin J.,Reinhard, John F.
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p. 133 - 138
(2007/10/03)
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- Thiazine and thiazepine containing compounds
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This invention is directed to compounds of the formula STR1 wherein X is a thiazine or thiazepine of the formula STR2 These compounds possess angiotensin converting enzyme inhibition activity and are thus useful as hypotensive agents.
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- ACYLAMINO OXO OR HYDROXY SUBSTITUTED ALKYLAMINO THIAZINES AND THIAZEPINES
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Compounds of the formula STR1 and X is an oxo substituted thiazine or thiazepine are disclosed. These compounds possess angiotensin converting enzyme inhibition activity and are thus useful as hypotensive agents.
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- THIAZINE AND THIAZEPINE CONTAINING COMPOUNDS
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This invention is directed to compounds of the formula STR1 wherein X is a thiazine or thiazepine selected from STR2 These compounds possess angiotensin converting enzyme inhibition activity and are thus useful as hypotensive agents.
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