QSAR study for a novel series of ortho disubstituted phenoxy analogues of α1-adrenoceptor antagonist WB4101

M. Pallavicini, L. Fumagalli, M. Gobbi, C. Bolchi, S. Colleoni, B. Moroni, A. Pedretti, C. Rusconi, G. Vistoli, E. Valoti

Research output: Contribution to journalArticlepeer-review


On the basis of the affinities at the α1a-, α1b- and α1d-adrenoceptors and the 5-HT1A receptor of a previous series of sixteen 2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes ortho monosubstituted at the phenoxy moiety, a number of ortho disubstituted analogues were designed, synthesized in both the enantiomeric forms and tested in binding assays on the same receptors. The affinity values of the new compounds 1-11 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known α1 antagonist WB4101, and of the ortho monosubstituted derivatives, suggesting some distinctive aspects of the interaction of the phenoxy moiety, in particular with the α1a-AR and the 5-HT1A receptor, of the monosubstituted and the disubstituted compounds. A classical quantitative structure-activity relationship (Hansch) analysis was applied to the whole set of the S enantiomers of the ortho mono- and disubstituted WB4101 analogues (26 compounds), finding a very good correlation for the α1a affinity. For this latter, a significant parabolic relationship was also found with the volume of the two ortho substituents. Diametrically opposite, the same relationships for the 5-HT1A exhibit low or insignificant correlation coefficients.

Original languageEnglish
Pages (from-to)1025-1040
Number of pages16
JournalEuropean Journal of Medicinal Chemistry
Issue number9
Publication statusPublished - Sep 2006


  • α-Adrenoreceptor
  • 5-HT receptor
  • Binding affinity
  • QSAR
  • WB4101 analogues

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science


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