Scott B Hoyt, Jerry Taylor, Clare London, Amjad Ali, Feroze Ujjainwalla, Jim Tata, Mary Struthers, Doris Cully, Tom Wisniewski, Ning Ren, Charlene Bopp, Andrea Sok, Andreas Verras, Daniel McMasters, Qing Chen, Elaine Tung, Wei Tang, Gino Salituro, Joe Clemas, Gaochao Zhou, Douglas MacNeil, Ruth Duffy, Yusheng Xiong
We report the discovery and hit-to-lead optimization of a structurally novel indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series displays potent inhibition of CYP11B2, high selectivity versus related steroidal and hepatic CYP targets, and lead-like physical and pharmacokinetic properties. On the basis of these and other data, the indazole series was progressed to lead optimization for further refinement.
April 8, 2017: Bioorganic & Medicinal Chemistry Letters