Design and synthesis of 1,3,5-trisubstituted 1,2,4-triazoles as CYP enzyme inhibitors

A series of 1,3,5-trisubstituted 1,2,4-triazoles was designed and synthesized as potential inhibitors of steroidogenic CYP enzymes. The 1,2,4-triazole is part of the core structure fixing the geometry of the substances. A pyridine moiety was introduced as heme-binder. The target compounds were synthesized in two to four steps using silver carbonate mediated ring closure and Suzuki cross coupling reaction as key synthetic transformations. Biological testing of the synthesized compounds for the inhibition of the most important steroidogenic CYPs revealed compounds 29a and 30 as moderate inhibitors of aldosterone synthase (CYP11B2). (C) 2011 Elsevier Ltd. All rights reserved.