Imidazole derivatives of pyrrolidonic and piperidonic as potential inhibitors of human placental aromatase in vitro.
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 Ki 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 microM, respectively (Ki AG= 77.0 microM).
Baroudi
M
M
Laboratoire de Chimie-Pharmacie, Université Joseph-Fourier, Grenoble I, France.
Robert
J
J
Luu-Duc
C
C
D000616:Aminoglutethimide / Q000494:pharmacology; D047072:Aromatase Inhibitors; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D010881:Piperidones / Q000737:chemistry / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology*; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010881:Piperidones; D011760:Pyrrolidinones; D000616:Aminoglutethimide; C029899:imidazole