Journal of Computer-Aided Molecular Design

, Volume 8, Issue 2, pp 211–220 | Cite as

A 3D QSAR approach to the search for geometrical similarity in a series of nonpeptide angiotensin II receptor antagonists

  • Laura Belvisi
  • Gianpaolo Bravi
  • Carlo Scolastico
  • Anna Vulpetti
  • Aldo Salimbeni
  • Roberto Todeschini
Research Papers

Summary

A 3D QSAR methodology based on the combined use of conformational analysis and chemometrics was applied to perform a comparative analysis of the 3D conformational features of 13 nonpeptide angiotensin II receptor antagonists showing different levels of binding affinity. Conformational analysis by using a molecular mechanics MM2 method was carried out for each of these structures to obtain conformational minima. These minima were described by ten interatomic distances which define the relative spatial disposition of five significant atoms belonging to relevant functional groups present in all the 13 molecules. The structure-activity relationship between the interatomic distances and the biological activity was then assessed by using chemometric methods (cluster analysis, principal component analysis, classification methods). With our indirect approach based on the search for geometrical similarity it was possible, even though structural information on the receptor active site was lacking, to identify the 3D geometrical requirements for the binding affinity of nonpeptide angiotensin II receptor inhibitors.

Key words

Binding affinity Structure-activity relationship Conformational analysis Chemometric methods Indirect drug design 

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Copyright information

© ESCOM Science Publishers B.V 1994

Authors and Affiliations

  • Laura Belvisi
    • 1
  • Gianpaolo Bravi
    • 1
  • Carlo Scolastico
    • 1
  • Anna Vulpetti
    • 1
  • Aldo Salimbeni
    • 2
  • Roberto Todeschini
    • 3
  1. 1.Dipartimento di Chimica Organica e Industriale Centro del C.N.R.MilanItaly
  2. 2.Istituto LusoFarmaco d'Italia S.p.a.MilanItaly
  3. 3.Dipartimento di Chimica Fisica e ElettrochimicaMilanItaly

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