Steroselective synthesis of some steroidal oxazolines, as novel potential inhibitors of 17alpha-hydroxylase-C17,20-lyase

Steroids. Nov-Dec 2009;74(13-14):1025-32. doi: 10.1016/j.steroids.2009.08.001. Epub 2009 Aug 8.

Abstract

17beta-Oxazolinyl steroids 7a-g and 8a-g were synthesized. The Lewis acid-catalysed reactions of (20R)-3beta-acetoxy-21-azidomethyl-20-hydroxypregn-5-ene with substituted aromatic aldehydes led to the formation of 3beta-acetoxyandrost-5-enes substituted in position 17beta with oxazolinyl residues (7a-g). Oppenauer oxidation of the 3beta-hydroxy-exo-heterocyclic steroids yielded the corresponding Delta(4)-3-ketosteroids. The inhibitory effects (IC(50)) of both 3-hydroxy compounds 7a-g and their Delta(4)-3-keto counterparts 8a-g on rat testicular C(17,20)-lyase were investigated with an in vitro radioligand incubation technique. The 3-chlorophenyl- (8d), and the 4-bromophenyl-17beta-(2-oxazolin-5-yl)androst-4-en-3-one derivatives (8f) were found to be modest inhibitors (IC(50)=4.8 and 5.0 microM, respectively).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Lyases / antagonists & inhibitors*
  • Male
  • Oxazoles / chemical synthesis*
  • Oxazoles / chemistry
  • Oxazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Stereoisomerism
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
  • Steroids / chemical synthesis*
  • Steroids / chemistry
  • Steroids / pharmacology
  • Testis / drug effects
  • Testis / enzymology

Substances

  • Enzyme Inhibitors
  • Oxazoles
  • Steroids
  • Steroid 17-alpha-Hydroxylase
  • Lyases