Synthesis and alpha1-adrenoceptor antagonist activity of tamsulosin analogues.

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Sagratini G, Angeli P, Buccioni M, Gulini U, Marucci G, Melchiorre C, Poggesi E, Giardina D

Synthesis and alpha1-adrenoceptor antagonist activity of tamsulosin analogues.

Eur J Med Chem. 2010 Dec;45(12):5800-7. doi: 10.1016/j.ejmech.2010.09.042. Epub 2010 Sep 25.

PubMed ID
20934789 [ View in PubMed
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Abstract

Tamsulosin (-)-1 is the most utilized alpha(1)-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 (-)-2-(-)-5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for alpha(1)-adrenoceptor subtypes. The benzyl analogue (-)-3, displaying a preferential antagonist profile for alpha1A-than alpha1D-and alpha1B-adrenoceptors, and a 12-fold higher potency at alpha1A-adrenoceptors with respect to the alpha1B subtype, may have improved uroselectivity compared to (-)-1.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TamsulosinAlpha-1A adrenergic receptorKi (nM)0.0501N/AN/ADetails
TamsulosinAlpha-1B adrenergic receptorKi (nM)0.631N/AN/ADetails
TamsulosinAlpha-1D adrenergic receptorKi (nM)0.1N/AN/ADetails