IMIDAZOLE DERIVATIVES OF PYRROLIDONIC AND PIPERIDONIC ACIDS AS POTENTIAL INHIBITORS OF HUMAN PLACENTAL AROMATASE IN-VITRO

Inhibitory activities towards human placental aromatase of novel pyrro lidinone and piperidinone drugs were investigated and compared with th ose of aminoglutethimide (AG) in vitro. All compounds showing a strong er inhibitory effect than this of AG had the following common structur al feature: an imidazole side-chain in C-3 position, with a substitute d or non-substituted aromatic ring in the C-2 position and an aliphati c chain (n-butyl or n-octyl) or a phenyl moiety on the nitrogen of the pyrrolidone or piperidone ring. When the C-3 side-chain did not bear any imidazole ring, no activity was observed. Respective K-i values fo r the competitive inhibition exerted by the more potent inhibitors 10, 11, 13 and 21 with androstenedione as substrate were 19.2, 20.3, 16.8 and 15.4 mu M, respectively (K-i AG = 77.0 mu M). (C) 1996 Elsevier S cience Ltd.