Steroidogenic cytochrome P450 (CYP) enzymes as drug targets: Combining substructures of known CYP inhibitors leads to compounds with different inhibitory profile

Abstract

Four out of six CYP enzymes involved in steroid biosynthesis are very interesting targets for the development of new drugs in order to treat a variety of severe illnesses. Herein we report on a novel approach for the discovery of hit compounds using new combinations of substructures of known CYP inhibitors. The synthesis of new scaffolds and their biological evaluation regarding inhibition of CYP17, CYP19, CYP11B1 and CYP11B2 are described. Thus, the very active (IC 50 = 114 and 100 nM) and selective (IC 50 >1000 nM) CYP11B2 inhibitors, compounds 4 and 5 , were obtained as well as the dual inhibitor 3 , reducing the activities of CYP19 and CYP11B2.