1613722-08-9Relevant academic research and scientific papers
Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from a fragment hit
George, Dawn M.,Breinlinger, Eric C.,Friedman, Michael,Zhang, Yang,Wang, Jianfei,Argiriadi, Maria,Bansal-Pakala, Pratima,Barth, Martine,Duignan, David B.,Honore, Prisca,Lang, Qingyu,Mittelstadt, Scott,Potin, Dominique,Rundell, Lian,Edmunds, Jeremy J.
, p. 222 - 236 (2015/03/03)
Protein kinase Cθ (PKCθ) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKCθ inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.
TRIAZINONE COMPOUNDS
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Paragraph 0927; 0928, (2014/08/06)
The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treati
