Principal components describing biological activities and molecular diversity of heterocyclic aromatic ring fragments

J Med Chem. 1996 Sep 27;39(20):4065-72. doi: 10.1021/jm960058h.

Abstract

Ten physicochemical variables have been calculated for each of 100 different aromatic rings. These variables were selected because of their potential involvement in the molecular recognition of drug-receptor binding interactions, and they include size, lipophilicity, dipole magnitude and orientation, HOMO and LUMO energies, and electronic point charges. A total of 59 different aromatic ring systems were studied including monocyclics and [5.5]-, [6.5]- and [6.6]-fused bicyclics. A principal components analysis of b1ese results generated four principal components which account for 84% of the total variance in the data. These principal components provide a quantitative measure of molecular diversity, and their relevance for structure-activity relationships is discussed. The principal components correlate with the in vitro biological activity of heterocyclic aromatic fragments within a series of previously reported HIV-1 reverse transcriptase inhibitors.

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • Heterocyclic Compounds / chemistry*
  • Molecular Structure
  • Polycyclic Aromatic Hydrocarbons / chemistry*
  • Reverse Transcriptase Inhibitors / chemistry
  • Software
  • Statistics as Topic
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds
  • Polycyclic Aromatic Hydrocarbons
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase