Discovery of Benzo[d]imidazole‐6‐sulfonamides as Bromodomain and Extra‐Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain

• DOI: 10.1002/cmdc.202200343
• Publication Date: 2022-08-30T12:12:23Z
• Authors: Alessandra Cipriano; Ciro Milite; Alessandra Feoli; Monica Viviano; Giacomo Pepe; Pietro Campiglia; Giuliana Sarno; Sarah Picaud; Satomi Imaide; Nikolai Makukhin; Panagis Filippako...; Alessio Ciulli; Sabrina Castellano; Gianluca Sbardella
• Keywords: BRD4

The bromodomain and extra-terminal (BET) family of proteins includes BRD2, BRD3, BRD4, the testis-specific protein, BRDT, each containing two N-terminal tandem (BRD) modules. Potent selective inhibitors targeting bromodomains are required to elucidate their biological role(s), with potential clinical applications. In this study, we designed synthesized a series benzimidazole-6-sulfonamides starting from azobenzene compounds MS436 (7 a) MS611 b) that exhibited preference for first (BD1) over second (BD2) BRD BET members. most-promising compound (9 showed good binding potency improved metabolic stability selectivity towards BD1 respect parent compounds.