N-(Pyridin-3-yl)benzamides as selective inhibitors of human aldosterone synthase (CYP11B2).
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.
Pharmaceutical and Medicinal Chemistry, Saarland University & Helmholtz Institute for Pharmaceutical Research Saarland, PO Box 15 11 50, D-66041 Saarbrücken, Germany.
Christina
C
Zimmer
Marieke
M
Hafner
Michael
M
Zender
Dominic
D
Ammann
Rolf W
RW
Hartmann
Carsten A
CA
Vock
D001141:Aromatase / Q000737:chemistry / Q000378:metabolism; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D001549:Benzamides; D004791:Enzyme Inhibitors; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase