N-(Pyridin-3-yl)benzamides as selective inhibitors of human aldosterone synthase (CYP11B2)

Christina Zimmer; Marieke Hafner; Michael Zender; Dominic Ammann; Rolf W Hartmann; Carsten A Vock

doi:10.1016/j.bmcl.2010.11.040

N-(Pyridin-3-yl)benzamides as selective inhibitors of human aldosterone synthase (CYP11B2)

Bioorg Med Chem Lett. 2011 Jan 1;21(1):186-90. doi: 10.1016/j.bmcl.2010.11.040. Epub 2010 Nov 12.

Authors

Christina Zimmer¹, Marieke Hafner, Michael Zender, Dominic Ammann, Rolf W Hartmann, Carsten A Vock

Affiliation

¹ Pharmaceutical and Medicinal Chemistry, Saarland University & Helmholtz Institute for Pharmaceutical Research Saarland, PO Box 15 11 50, D-66041 Saarbrücken, Germany.

PMID: 21129965
DOI: 10.1016/j.bmcl.2010.11.040

Abstract

A series of 23 N-(Pyridin-3-yl)benzamides was synthesized and evaluated for their potential to inhibit human steroid-11β-hydroxylase (CYP11B1) and human aldosterone synthase (CYP11B2). The most potent and selective CYP11B2 inhibitors (IC(50) values 53-166 nM) were further evaluated for their potential to inhibit human CYP17 and CYP19, and no inhibition was observed. Clear evidence was shown for N-(Pyridin-3-yl)benzamides to be a highly selective class of CYP11B2 inhibitors in vitro.

MeSH terms

Aromatase / chemistry
Aromatase / metabolism
Benzamides / chemical synthesis
Benzamides / chemistry*
Benzamides / pharmacology
Cytochrome P-450 CYP11B2 / antagonists & inhibitors*
Cytochrome P-450 CYP11B2 / metabolism
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Humans
Steroid 11-beta-Hydroxylase / antagonists & inhibitors
Steroid 11-beta-Hydroxylase / metabolism
Steroid 17-alpha-Hydroxylase / antagonists & inhibitors
Steroid 17-alpha-Hydroxylase / metabolism
Structure-Activity Relationship

Substances

Benzamides
Enzyme Inhibitors
Aromatase
Steroid 17-alpha-Hydroxylase
Cytochrome P-450 CYP11B2
Steroid 11-beta-Hydroxylase