α 1 ‐ and α 2 ‐Adrenoreceptor Antagonist Profiles of 1‐ and 2‐[ ω ‐(4‐Arylpiperazin‐1‐yl)alkyl]‐1,2,3‐benzotriazoles

A series of pharmacologically interesting 1‐ and 2‐[ ω ‐(4‐arylpiperazin‐1‐yl)alkyl]‐1,2,3‐benzotriazoles, compounds 1 – 27 , were synthesized ( Scheme ) and subjected to various biological studies to identify structure–activity relationships (SAR). The new compounds were found to exhibit good non‐selective binding affinity towards the α 1 ‐adrenoreceptor ( Table 1 ). In several cases, high functional antagonism was observed towards the α 1A ‐, α 1B ‐, and α 1D ‐adrenoreceptor subtypes ( Table 2 ). The selectivity for these three subtypes was comparable with or superior to that displayed by the standard drug prazosin. The most‐common selectivity rank order was α 1D > α 1B > α 1A , followed by α 1B > α 1D > α 1A . In functional experiments, antagonism towards the α 2 ‐adrenoreceptor was generally low; however, a few compounds were endowed with significant antagonist properties (p A 2 values of up to 7.87).