Synthesis of Z- and E-1-methyl-2-(1-hydroximinoethyl)-6-methoxy-3,4-dihydronaphthalene and evaluation as inhibitors of 17 alpha-hydroxylase-C17,20-lyase (P450 17)

Arch Pharm (Weinheim). 1997 Nov;330(11):359-61. doi: 10.1002/ardp.19973301108.

Abstract

The synthesis and biological evaluation of Z- and E-1-methyl-2-(1-hydroximinoethyl)-6-methoxy-3,4-dihydro-naphtha len e (Z-1 and E-1) as nonsteroidal inhibitors of 17 alpha-hydroxylase-C17,20-lyase (P450 17, CYP 17) is described. Z-1 and E-1 were separated by column chromatography and identified by 1H NMR. The synthesis of the key compound 3 was accomplished by a new reaction acetylating the 1-methyl-6-methoxy-3,4-dihydronaphthalene compound 2 under Friedel-Crafts conditions. Compound 2 was obtained from the 1-tetralone via Wittig reaction. Using a microsomal fraction of human testicular enzyme, Z-1 and E-1 inhibited the target enzyme only marginally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Imines / chemical synthesis*
  • Imines / pharmacology*
  • Male
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / pharmacology*
  • Stereoisomerism
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*

Substances

  • 1-methyl-2-(1-hydroxyiminoethyl)-6-methoxy-3,4-dihydronaphthalene
  • Enzyme Inhibitors
  • Imines
  • Naphthalenes
  • Steroid 17-alpha-Hydroxylase