http://jcps.bjmu.edu.cn

• Full Papers • Previous Articles     Next Articles

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

Zhu Na, Zhao Na, Lei Xiaoping, Ling Yangzhi*, Venkatech Hundratta, Angela Brodie

  

  1. 1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing 100082
    2. Department of Pharmacology & Experimental Therapeutics, School of Medicine, University of Maryland. Baltimore, Maryland 21201
  • Received:2000-08-19 Revised:2001-01-08 Online:2001-03-15 Published:2001-03-15
  • Contact: Ling Yangzhi*

Abstract:

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 of methyl 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 6ac and 9 as expected. The further pharmacological study of 6c is in progress.

Key words: 17-Oxazolyl androstene, P45017α Inhibitors, Prostate cancer, Bioisosterism

Supporting: