1-(5-叔丁基-2-苯并噁唑甲基)-4-(2-取代芳氧基乙基)哌嗪的设计、合成及生物活性

Design,synthesis and biological activities of 1-(5-t-butyl-2-benzoxazolemethyl)-4-aryloxyalkyl-piperazine as α_1 adrenoceptor antagonists

目的:寻找新的苯并唑类α1受体拮抗剂。方法:结合α1-受体拮抗剂的构效关系研究,以4-叔丁基-2-氨基酚和取代苯酚为原料,分别经缩合、关环、Williamson醚合成、取代、成盐等反应合成目标化合物,测定α1受体拮抗活性。结果:设计合成了12个新的目标化合物,结构经ESI-MS1、H NMRI、R及HRMS确证。初步药理活性实验表明,7个目标物pA2值大于7.00,有良好的1α受体拮抗活性。结论:5-叔丁基苯并唑芳氧烷基哌嗪类化合物是一类新型的具有潜在价值的α1受体拮抗剂。

Aim： To find new α1-adrenoceptor antagonists bearing benzoxazole moiety. Methods： Target compounds were synthesized from 4-t-butyl-2-aminophenol v/a condensation, cycle-closing, substitution and salifieafion; preliminary biological activities were also evaluated. ResultS：Twelve of the new target compounds were synthesized and their structures were confirmed by ESI-MS, IR, 1H NMR and HRMS. Biological assay showed pA2 values of seven target compounds were greater than 7.00. Conclusion： 1-（5- t-butyl-2-benzoxazolemethyl）-4-aryloxyalkyl-piperazine is potentially a new candidate for α1 adrenoceptor antagonist.