On the basis of the affinities at the a1a-, a1b- and a1d-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 no. of ortho disubstituted analogs were designed, synthesized in both the enantiomeric forms and tested in binding assays on the same receptors. The affinity values of the new compds. 1-11 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analog, the well-known a1 antagonist WB4101, and of the ortho monosubstituted derivs., suggesting some distinctive aspects of the interaction of the phenoxy moiety, in particular with the a1a-AR and the 5-HT1A receptor, of the monosubstituted and the disubstituted compds. A classical quant. structure-activity relationship (Hansch) anal. was applied to the whole set of the S enantiomers of the ortho mono- and disubstituted WB4101 analogs (26 compds.), finding a very good correlation for the a1a affinity. For this latter, a significant parabolic relationship was also found with the vol. of the two ortho substituents. Diametrically opposite, the same relationships for the 5-HT1A exhibit low or insignificant correlation coeffs

QSAR study for a novel series of ortho disubstituted phenoxy analogues of a1-adrenoceptor antagonist WB4101 / M. Pallavicini, L. Fumagalli, M. Gobbi, C. Bolchi, S. Colleoni, B. Moroni, A. Pedretti, C. Rusconi, G. Vistoli, E. Valoti. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 41:9(2006), pp. 1025-1040.

QSAR study for a novel series of ortho disubstituted phenoxy analogues of a1-adrenoceptor antagonist WB4101

M. Pallavicini;L. Fumagalli;C. Bolchi;S. Colleoni;A. Pedretti;G. Vistoli;E. Valoti
2006

Abstract

On the basis of the affinities at the a1a-, a1b- and a1d-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 no. of ortho disubstituted analogs were designed, synthesized in both the enantiomeric forms and tested in binding assays on the same receptors. The affinity values of the new compds. 1-11 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analog, the well-known a1 antagonist WB4101, and of the ortho monosubstituted derivs., suggesting some distinctive aspects of the interaction of the phenoxy moiety, in particular with the a1a-AR and the 5-HT1A receptor, of the monosubstituted and the disubstituted compds. A classical quant. structure-activity relationship (Hansch) anal. was applied to the whole set of the S enantiomers of the ortho mono- and disubstituted WB4101 analogs (26 compds.), finding a very good correlation for the a1a affinity. For this latter, a significant parabolic relationship was also found with the vol. of the two ortho substituents. Diametrically opposite, the same relationships for the 5-HT1A exhibit low or insignificant correlation coeffs
α1-Adrenoreceptor; 5-HT1A receptor; Binding affinity; QSAR; WB4101 analogues
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/25922
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