Synthesis and α1-antagonist activity of new prazosin- and benextramine-related tetraamine disulfides

Article abstract of DOI:10.1016/S0223-5234(97)84357-7

Tetraamine disulfides 1-10 were designed by combining the structural features of benextramine, an irreversible α₁/α₂-adrenoceptor antagonist, and prazosin, a selective competitive α₁-antagonist. Their biological profile was assessed by functional and binding assays. In rat vas deferens functional experiments, tetraamine disulfides 1-10 displayed a marked selectivity at α₁-adrenoceptors. Furthermore, they acted as competitive antagonists at α₁-adrenoceptors and weak noncompetitive (irreversible) antagonists at α₂-adrenoceptors. In binding assays, performed at α₁-adrenoceptors of rat liver (α(1B)) and submaxillary gland (α(1A)), compound 5 showed an 11-fold selectivity for α(1B)-adrenoceptors in contrast to both prazosin and benextramine, which were not selective or selective for the α(1A)-subtype respectively.