Antiandrogenic Steroidal Sulfonyl Heterocycles. Utility of Electrostatic Complementarity in Defining Bioisosteric Sulfonyl Heterocycles

J Med Chem. 1992 May 15;35(10):1663-70. doi: 10.1021/jm00088a001.

Abstract

Complementarity of electrostatic potential surface maps was utilized in defining bioisosteric steroidal androgen receptor antagonists. Semiempirical and ab initio level calculations performed on a series of methanesulfonyl heterocycles indicated the requirement for a partial negative charge at the heteroatom attached to C-3 of the steroid nucleus to attain androgen receptor affinity. Synthesis and testing of six heterocycle A-ring-fused dihydroethisterone derivatives support this hypothesis, and we have identified two new androgen receptor antagonists of this class.

MeSH terms

  • Androgen Antagonists / chemistry*
  • Androgen Antagonists / classification
  • Androgen Receptor Antagonists
  • Electrochemistry
  • Heterocyclic Compounds / chemistry*
  • Receptors, Androgen / metabolism
  • Substrate Specificity
  • X-Ray Diffraction

Substances

  • Androgen Antagonists
  • Androgen Receptor Antagonists
  • Heterocyclic Compounds
  • Receptors, Androgen