1-Alkyl analogues of aminoglutethimide. Comparative inhibition of cholesterol side chain cleavage and aromatase and metabolism of the 1-propyl derivative, a highly selective inhibitor of aromatase.

摘要: Abstract A homologous series of 1- n -alkyl-derivatives aminoglutethimide (AG) has been synthesised and tested for inhibitory activity towards the cholesterol side chain cleavage enzyme (desmolase) from bovine adrenals human placental aromatase in an attempt to find a selective inhibitor. Activity against desmolase declined ic 50 value 30 mM parent drug 220 -propyl derivative but increased again thereafter. Against aromatase, was least methyl ethyl derivatives highest ( = 1.6 m M ) hexyl octyl analogues. The optimal ratio : 44 found derivative, which therefore selected preliminary metabolism studies using rat mouse liver microsomes hepatocytes these species vivo . There were parallels with AG, most notably analogous formation arylhydroxylamine mouse.