A number of (S)- and (R)-2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes unsubstituted or ortho monosubstituted at the phenoxy moiety were synthesized and tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR alpha(1d)-AR and the 5-HT1A receptor. The affinity values of the new compounds 1-16 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known alpha(1) antagonist WB4101, finding that the unsubstituted derivative (S)-1 and the o-methyl, the o-t-butyl, the o-fluoro and the o-methoxy derivatives, (S)-2, (S)-4, (S)-8 and (S)-16, respectively, display a significantly specific 5-HT1A affinity, very close, with the exception of (S)-4, to the almost nanomolar one of (S)-WB4101. Otherwise sensible affinity decreases were recorded for the three alpha(1)-AR subtypes. A classical quantitative structure-activity relationship (Hansch) analysis was successfully applied to compounds (S)-1 to (S)-16 and (S)-WB4101 to rationalize such binding data.

QSAR study for a novel series of ortho monosubstituted phenoxy analogues of alpha(1)-adrenoceptor antagonist WB4101 / L. Fumagalli, C. Bolchi, S. Colleoni, M. Gobbi, B. Moroni, M. Pallavicini, A. Pedretti, L. Villa, G. Vistoli, E. Valoti. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 13:7(2005), pp. 2547-2559.

QSAR study for a novel series of ortho monosubstituted phenoxy analogues of alpha(1)-adrenoceptor antagonist WB4101

L. Fumagalli;C. Bolchi;S. Colleoni;B. Moroni;M. Pallavicini;A. Pedretti;L. Villa;G. Vistoli;E. Valoti
2005

Abstract

A number of (S)- and (R)-2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes unsubstituted or ortho monosubstituted at the phenoxy moiety were synthesized and tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR alpha(1d)-AR and the 5-HT1A receptor. The affinity values of the new compounds 1-16 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known alpha(1) antagonist WB4101, finding that the unsubstituted derivative (S)-1 and the o-methyl, the o-t-butyl, the o-fluoro and the o-methoxy derivatives, (S)-2, (S)-4, (S)-8 and (S)-16, respectively, display a significantly specific 5-HT1A affinity, very close, with the exception of (S)-4, to the almost nanomolar one of (S)-WB4101. Otherwise sensible affinity decreases were recorded for the three alpha(1)-AR subtypes. A classical quantitative structure-activity relationship (Hansch) analysis was successfully applied to compounds (S)-1 to (S)-16 and (S)-WB4101 to rationalize such binding data.
alpha(1)-antagonist, WB4101, WB4101 analogues, alpha(1)-adrenergic receptor subtypes, 5-HT1A serotoninergic receptor, binding affinity, QSAR analysis
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/2434/6032
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