Discovery of indazole aldosterone synthase (CYP11B2) inhibitors as potential treatments for hypertension. Issue 11 (1st June 2017)

• Record Type: Journal Article
• Authors: Hoyt, Scott B.; Taylor, Jerry; London, Clare; Ali, Amjad; Ujjainwalla, Feroze; Tata, Jim; Struthers, Mary; Cully, Doris; Wisniewski, Tom; Ren, Ning; Bopp, Charlene; Sok, Andrea; Verras, Andreas; McMasters, Daniel; Chen, Qing; Tung, Elaine; Tang, Wei; Salituro, Gino; Clemas, Joe; Zhou, Gaochao; MacNeil, Douglas; Duffy, Ruth; Xiong, Yusheng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 11(2017)
• Page Start: 2384
• Page End: 2388
• Publication Date: 2017-06-01
• Subjects: Aldosterone synthase -- CYP11B2 -- Indazole -- Hit-to-lead -- Hypertension; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.04.021
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We report the discovery and hit-to-lead optimization of a structurally novel indazole series of CYP11B2 inhibitors. Benchmark compound34 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.