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).
Boido
Alessandro
A
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova.
Budriesi
Roberta
R
Boido
Caterina Canu
CC
Ioan
Pierfranco
P
Terranova
Emanuela
E
Chiarini
Alberto
A
Sparatore
Fabio
F
D000316:Adrenergic alpha-Agonists / Q000737:chemistry* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D014230:Triazoles