Synthesis and evaluation of steroidal hydroxamic acids as inhibitors of P450 17 (17 alpha-hydroxylase/C17-20-lyase).
With the aim of developing new inhibitors of 17 alpha-hydroxylase/C17,20-lyase (P450 17, CYP 17), two steroidal hydroxamic acids (compounds 2 and 3) were synthesized and evaluated as inhibitors of CYP 17. The synthesis was performed using carboxylic acids as starting material to give acid chlorides which were reacted with N,N,O-tris(trimethylsilyl) hydroxylamine. Using microsomal fractions of human and rat testes and progesterone as a substrate, both compounds moderately inhibited the human and rat enzyme.
Haidar
S
S
Universität des Saarlandes, P.O. Box 151150, D-66041 Saarbrücken, Germany.
Klein
C D
CD
Hartmann
R W
RW
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D013254:Steroid 17-alpha-Hydroxylase