Structure-Activity Relationships for Prazosin and WB 4101 Analogues as α1-Adrenoreceptor Antagonists

Article abstract of DOI:10.1021/jm00147a042

Several α-adrenoreceptor antagonists were prepared by coupling one of the two moieties of WB 4101 (1) with one of the two moieties of prazosin (2).Their blocking activity and relative selectivity on α₁- and α₂-adrenoreceptors were evaluated in the isolated rat vas deferens.Although retaining a significant selectivity toward α₁-adrenoreceptors, all the drugs were weaker antagonists than the parent compounds 1 and 2.Opening the piperazine ring of 2 gave 3, which displayed a very high activity and selectivity toward α₁-adrenoreceptors (α₁/α₂ = 3890).This may have relevance in understanding the mode of action of prazosin.In addition, 3 may represent a valuable tool in the characterization of α-adrenoreceptor subtypes.