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Synfacts 2021; 17(12): 1314
DOI: 10.1055/s-0041-1737090
Synthesis of Natural Products and Potential Drugs

Synthesis of BMS-986158

Rezensent(en):
Philip Kocienski
Gavai AV. * et al. Bristol Myers Squibb Company, Princeton, USA
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;
64: 14247-14265
DOI: 10.1021/acs.jmedchem.1c00625
CrossrefPubMedSuche in Google Scholar
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Key words

BMS-986158 - Stille coupling - Chan–Lam coupling - copper catalysis - palladium-catalyzed C–H activation - Mitsunobu reaction

Significance

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.


 

Comment

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.


 

 

Publikationsverlauf

Artikel online veröffentlicht:
17. November 2021

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