The Synthesis of Some 17-（2＇-Oxazolyl）-androsta-5,16-diene Deriva-tives as 17α-Hydroxylase／C17,20 -Lyase Inhibitors

Several 4‘- and 5‘-substituted 17-(2‘-oxazolyl)-androsta-5,16-diene derivatives were designed and synthesized as inhibitors of 17α-hydroxylase/C17,20 -Lyase (P45017α) for the treatment of prostatic cancer, the results of the preliminary pharmacological screening showed that compound 6c, i.e. 17-(2‘-oxazoly)-androsta-5,16-diene-3-ol was a strong inhibitor, comparable with that of the reference compound VN-85. The introduction ofmethyl or phenyl group at the 4‘ or 5‘ position of oxazole ring decreased the activity. The in vitro activities of 3- acetate 5a-c and 8 were lower than their 3-ol counterparts 6a-c and 9 as expected. The further pharmacological study of 6c is in progress.     

Syntheses and Pharmacological Activity of Some 17-[（2＇-Substituted）-4＇-pyrimidyl]androstene Derivatives As Inhibitors of Human 17α-Hydroxylase／C17,20-Layse＊

17-Heterocyclic substituted androstene derivatives have been found to be potent inhibitors for human testicular microsomal 17α-hydroxylase/C17.20-layse, which have potential usage in the treatment of benign prostatic hypertrophy(BPH) and prostatic cancer. In order to further investigate their structure-activity relationships, seven new 17-[(2‘-substituted)-4‘-pyrimidyl]androstene derivatives were designed and synthesized. The structures of the compounds were confirmed by IR, ^1H NMR, elemental analysis or MS measurements. The results of the pharmacological activity tests showed that‘compound 5 is a potent inhibitor for P45017α with IC50 225 nmol.L^-1.