Synthesis and α(1)-adrenoceptor antagonist activity of tamsulosin analogues

Sagratini, Gianni; Angeli, Piero; Buccioni, Michela; Gulini, U; Marucci, Gabriella; Melchiorre, C; Poggesi, E; Giardinà, D.

Tamsulosin (-)- 1 is the most utilized a1-adrenoceptor antagonist in the benign prostatic hyperplasia therapy owing to its uroselective antagonism and capability in relieving both obstructive and irritative lower urinary tract symptoms. Here we report the synthesis and pharmacological study of the homochiral (-)- 1 analogues (-)- 2e(-)- 5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for a1-adrenoceptor subtypes. The benzyl analogue (-)- 3, displaying a preferential antagonist profile for a1A-than a1D-and a1B-adrenoceptors, and a 12-fold higher potency at a1A-adrenoceptors with respect to the a1B subtype, may have improved uroselectivity compared to (-)- 1.

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Titolo:	Synthesis and α(1)-adrenoceptor antagonist activity of tamsulosin analogues
Autori:	SAGRATINI, Gianni ANGELI, Piero BUCCIONI, Michela Gulini U MARUCCI, Gabriella Melchiorre C Poggesi E Giardinà D. mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2010
Rivista:	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Abstract:	Tamsulosin (-)- 1 is the most utilized a1-adrenoceptor antagonist in the benign prostatic hyperplasia therapy owing to its uroselective antagonism and capability in relieving both obstructive and irritative lower urinary tract symptoms. Here we report the synthesis and pharmacological study of the homochiral (-)- 1 analogues (-)- 2e(-)- 5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for a1-adrenoceptor subtypes. The benzyl analogue (-)- 3, displaying a preferential antagonist profile for a1A-than a1D-and a1B-adrenoceptors, and a 12-fold higher potency at a1A-adrenoceptors with respect to the a1B subtype, may have improved uroselectivity compared to (-)- 1.
Handle:	http://hdl.handle.net/11581/203200
Appare nelle tipologie:	Articolo

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