1-(1,4-苯并二噁烷-2-羰基)-4-取代芳氧烷基哌嗪类α_1受体拮抗剂的合成及其生物活性

Synthesis and biological activity of 1-(1,4-benzodioxan-2-yl-carbonyl)-4-aryloxy-alkyl-piperazine as α_1-adrenoceptor antagonists

目的寻找新的1,4-苯并二烷类α1受体拮抗剂。方法选用1,4-苯并二烷为母核,以儿茶酚和取代苯酚为原料,分别经关环、水解、成酰胺、取代、成盐等反应合成目标化合物,并测定该类化合物α1受体拮抗活性。结果与结论设计合成了13个新化合物,结构经ESI-MS、1H-NMR、IR及HR-MS确证。初步药理活性实验表明,其中8个目标化合物的pA2值大于6.00,具有良好的α1受体拮抗活性,有进一步研究的价值。

Aim To find new α1-adrenoceptor antagonists bearing 1, 4-benzodioxane moiety. Methods The target compounds were synthesized from catechol via ring-closing, hydrolysis, amidation, substitution and salt formation. Preliminary biological activities were evaluated. Result and conclusion Thirteen new target compounds were synthesized and their structures were confirmed by ESI-MS, IR, ^1H-NMR, and HR-MS. Biological assay showed the pA2 values of eight target compounds were greater than 6.00. Preliminary bioassay suggested that most of the target compounds showed potent blocking activity to α1-AR and 1-（1,4- benzodioxan-2-yl-carbonyl）-4-aryl-oxyalkylpiperazine should be a kind of valuable α1-adrenoceptor antagonists to be investigated.