Design of mechanism-based inactivators of human placental aromatase

Cancer Res. 1982 Aug;42(8 Suppl):3322s-3326s.

Abstract

This article reviews the design and study, in our own laboratory and in other laboratories, of new 10 beta-substituted analogs of estr-4-ene-3,17-dione. These compounds, along with a number of known analogs, have been evaluated as reversible or irreversible inhibitors of human placental microsomal aromatase. The only irreversible inhibitors in the group surveyed here are the 10 beta-difluoromethyl, 10 beta-propargyl, and 10 beta-allenyl derivatives of estr-4-ene-3,17-dione. Possible mechanisms for the inactivation processes are discussed. The effects of incorporating the 19-methyl group of adrost-4-ene-3,17-dione into a ring of three, four, five or six carbons are also described.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aromatase Inhibitors*
  • Estrenes / pharmacology*
  • Female
  • Humans
  • Microsomes / enzymology
  • Oxidoreductases / antagonists & inhibitors*
  • Placenta / enzymology*
  • Pregnancy
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Aromatase Inhibitors
  • Estrenes
  • Oxidoreductases