Endothelin antagonists: search for surrogates of methylendioxyphenyl by means of a Kohonen neural network

Bioorg Med Chem Lett. 1998 Jan 6;8(1):11-6. doi: 10.1016/s0960-894x(97)10150-0.

Abstract

The methylendioxyphenyl group, present in a number of potent endothelin receptor antagonists, could have undesirable metabolic interactions with cytochrome P450 in vivo. Using a self-organizing neural network we analysed the features of molecular electrostatic potentials of several endothelin receptor ligands. A library of small "fragments and functional groups" together with their corresponding Kohonen maps was generated. By means of this Kohonen map library we discovered the benzothiadiazole group as a surrogate for methylendioxyphenyl.

MeSH terms

  • Cytochrome P-450 Enzyme System / metabolism
  • Dioxoles / chemistry*
  • Dioxoles / metabolism
  • Endothelins / antagonists & inhibitors*
  • Neural Networks, Computer*
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Dioxoles
  • Endothelins
  • methylendioxyphenyl
  • Cytochrome P-450 Enzyme System