Synthesis and α1-adrenoceptor antagonist activity of tamsulosin analogues

Abstract Tamsulosin (−)- 1 is the most utilized α 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 α 1 -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 .