Document Report Card
Basic Information
ID: ALA4665894
Journal: ACS Med Chem Lett
Title: Driving Potency with Rotationally Stable Atropisomers: Discovery of Pyridopyrimidinedione-Carbazole Inhibitors of BTK.
Authors: Srivastava AS,Ko S,Watterson SH,Pattoli MA,Skala S,Cheng L,Obermeier MT,Vickery R,Discenza LN,D'Arienzo CJ,Gillooly KM,Taylor TL,Pulicicchio C,McIntyre KW,Yip S,Li P,Sun D,Wu DR,Dai J,Wang C,Zhang Y,Wang B,Pawluczyk J,Kempson J,Zhao R,Hou X,Rampulla R,Mathur A,Galella MA,Salter-Cid L,Barrish JC,Carter PH,Fura A,Burke JR,Tino JA
Abstract: Bruton's tyrosine kinase (BTK) has been shown to play a key role in the pathogenesis of autoimmunity. Therefore, the inhibition of the kinase activity of BTK with a small molecule inhibitor could offer a breakthrough in the clinical treatment of many autoimmune diseases. This Letter describes the discovery of BMS-986143 through systematic structure-activity relationship (SAR) development. This compound benefits from defined chirality derived from two rotationally stable atropisomeric axes, providing a potent and selective single atropisomer with desirable efficacy and tolerability profiles.
CiteXplore: 33214829