Alpha1- and alpha2-adrenoreceptor antagonist profiles of 1- and 2-[omega-(4-arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles.

A series of pharmacologically interesting 1- and 2-[omega-(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 alpha1-adrenoreceptor (Table 1). In several cases, high functional antagonism was observed towards the alpha1A-, alpha1B-, and alpha1D-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 alpha1D > alpha1B > alpha1A, followed by alpha1B > alpha1D > alpha1A. In functional experiments, antagonism towards the alpha2-adrenoreceptor was generally low; however, a few compounds were endowed with significant antagonist properties (pA2 values of up to 7.87).

Antiinflammatory and antinociceptive activities of some benzotriazolylalkanoic acids.

Sets of benzotriazol-1/2-ylalkanoic acids (1, 2, 3) and benzotriazol-1-yloxyalkanoic acids (4, 5) were prepared and tested for antiinflammatory activity; when significant activity was observed also the antinociceptive activity was explored. While the acids of structure 1, 4 and 5 were devoid of antiinflammatory action, most 2-(benzotriazol-1/2-yl)propionic acids (2, 3) exhibited significant activity as antiinflammatory and antinociceptive agents, with compound 2c and 3a being the most active in the two assays, respectively. The dextrorotatory enantiomer of 2c ((+)-2c) was also prepared and found to be practically as active as the racemic mixture, though some differences in the steepness of the dose-response curves were observed.