Synthesis and α1-adrenoceptor antagonist activity of tamsulosin analogues

Article abstract of DOI:10.1016/j.ejmech.2010.09.042

Tamsulosin (-)-1 is the most utilized α₁-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 α₁-adrenoceptor subtypes. The benzyl analogue (-)-3, displaying a preferential antagonist profile for α_1A-than α_1D-and α_1B- adrenoceptors, and a 12-fold higher potency at α_1A- adrenoceptors with respect to the α_1B subtype, may have improved uroselectivity compared to (-)-1.