Discovery of indazole aldosterone synthase (CYP11B2) inhibitors as potential treatments for hypertension.
Bioorganic & Medicinal Chemistry Letters(2017)
Abstract
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.
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Key words
Aldosterone synthase,CYP11B2,Indazole,Hit-to-lead,Hypertension
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