Development and evaluation of a pharmacophore model for inhibitors of aldosterone synthase (CYP11B2)

Recently, we proposed inhibition of aldosterone synthase (CYP11B2) as a novel strategy for the treatment of congestive heart failure and myocardial fibrosis and synthesized a large number of inhibitors. In this work, a pharmacophore model for CYP11B2 inhibitors was developed by superimposition of active and non-active compounds. This model was confirmed by the synthesis of two pyridyl substituted acenaphthene derivatives (A,B). This new class of compounds as well as the pharmacophore could be helpful for the discovery of novel inhibitors.

Graphical abstractThe development of a pharmacophore model through alignment of a subset of inhibitors and non-inhibitors of aldosterone synthase (CYP11B2) is described as well as its validation by synthesis and biological evaluation of two novel compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide