吡啶氧基苯基哌嗪取代丙醇类α_1受体拮抗剂的合成

Synthesis of 1-(pyridin-3-yloxyl)-3-(4-phenylpiperazin-1-yl)-propan-2-ol as α_1 receptor antagonist

目的设计合成具有α1受体拮抗活性的1-(吡啶-3-氧)-3-(4-苯基-1-哌嗪)-2-丙醇类化合物。方法在NaH存在下,3-羟基吡啶衍生物(1)和3-氯-1,2-环氧丙烷(2)在DMF中于60℃反应生成3-(吡啶-3-氧)-1,2-环氧丙烷(3),再经苯基哌嗪对环氧开环,合成了1-(吡啶-3-氧)-3-(4-苯基-1-哌嗪)-2-丙醇衍生物(4)。所合成的化合物经MS、1H-和13C-NMR谱确证其结构。结果采用两步反应合成了1-(吡啶-3-氧)-3-(4-苯基-1-哌嗪)-2-丙醇衍生物,这些化合物具有明显的α1受体拮抗活性。结论该合成方法适合于吡啶氧基苯基哌嗪取代丙醇类衍生物的合成,总收率达68%以上。

Objective To design and synthesize 1-（pyridin-3-yloxyl）-3-（4-phenylpiperazin-1-yl）- propan-2-ol derivatives with α1 receptor antagonistic activity. Methods In the presence of Nail, 3-（pyridin-3-yloxyl）-l, 2-e- poxypropane （3） was prepared from 3-hydroxylpyridine derivatives （1） and 3-chloro-1, 2-epoxypropane （2） in DMF at 60~C, followed by epoxy cleavage with phenylpiperazine, leading to the synthesis of 1-（pyridin-3-yloxyl）-3-（4- phenylpiperazin-l-yl）- propan-2-ol derivatives （4）. The structures of target compounds were confirmed by MS, IH- and 13C-NMR data. Results 1-（pyridin-3-yloxyl）-3-（4-phenylpiperazin-l-yl）-propan-2-o1 derivatives were synthe- sized by two steps. The eompounds showed potent α1 receptor antagonistic activity. Conclusion The reported method is effective to the synthesis of 1-（pyridin-3-yloxyl）-3-（4-phenylpiperazin-l-yl）-propan-2-ol derivatives with total yield above 68%.