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Synthesis of BMS-986158
Discovery and Preclinical Pharmacology of an Oral Bromodomain and Extra-Terminal (BET) Inhibitor Using Scaffold-Hopping and Structure-Guided Drug Design.
J. Med. Chem. 2021;
Key wordsBMS-986158 - Stille coupling - Chan–Lam coupling - copper catalysis - palladium-catalyzed C–H activation - Mitsunobu reaction
BMS-986158 is an inhibitor of the bromodomain and extra-terminal (BET) family of adaptor proteins that are involved in the transcriptional regulation of key oncogenes. It has entered phase 1/2a clinical trials in patients with advanced cancers and hematologic indications including myelofibrosis.
Key steps in the small-scale discovery synthesis of the 5H-pyrido[3,2-b]indole core of BMS-986158 are (1) the copper-catalyzed oxidative coupling of the chloropyridine C with the boronic acid D (Chan–Lam coupling) and (2) the palladium-catalyzed C–H activation reaction E → F.
17 November 2021 (online)
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