Imidazole derivatives of pyrrolidonic and piperidonic acids as potential inhibitors of human placental aromatase in vitro

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 57; no. 1; pp. 73 - 77
• Main Authors: Baroudi, Moomen, Robert, Jacqueline, Luu-Duc, Cuong
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1996; Elsevier Science
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Oxidoreductases; Human; Enzyme inhibitor; Imidazole derivatives; Placenta; Estrogen synthase; Enzyme
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/0960-0760(95)00253-7

Inhibitory activities towards human placental aromatase of novel pyrrolidinone and piperidinone drugs were investigated and compared with those of aminoglutethimide (AG) in vitro. All compounds showing a stronger inhibitory effect than this of AG had the following common structural feature: an imidazole side-chain in C-3 position, with a substituted or non-substituted aromatic ring in the C-2 position and an aliphatic 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 for 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 μM, respectively ( K i AG = 77.0 μM).