New aromatase inhibitors.: Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives

We report herein the design and the synthesis of some aryl-substituted pyrrolizine and indolizine derivatives, on the basis of a hypothetical pharmacophore structure designed to fit the catalytic site of the human cytochrome P450 aromatase. The in vitro biological evaluation of these compounds allowed us to point out two new potent non-steroidal aromatase inhibitors, MR 20494 and MR 20492, with IC50 values in the range of 0.1 mu M. (C) 2000 Elsevier Science Ltd. All rights reserved.