4-((4-((2-取代苯氧基)乙基)-1-哌嗪)-甲基)-1,2-二氢喹啉-2-酮类化合物的合成及体外α-受体拮抗活性

SYNTHESIS AND ANTI α-ADRENOCEPTOR ACTIVITY IN VITRO OF 4-((4-((2-SUBSTITUTEDPHENOXY)ETHYL)-1-PIPERAZINYL) METHYL)-1,2-DIHYDRO-QUINOLINE-2-ONE COMPOUNDS

摘要: 目的研究DDPH类似物1,2-二氢喹啉-2-酮类化合物的合成及其体外α-受体拮抗活性。方法通过酰化、溴代、环合和取代反应等合成目的物;推测了异常中间体3-溴-4-溴甲基-1,2-二氢喹啉-2-酮(5)和3-溴-4-甲基-1,2-二氢喹啉-2-酮(6)的生成机理;测定目的物的体外α-受体拮抗活性。结果设计、合成了12个新化合物II_1～6和IV_1～6,其中6个目的物1,2-二氢喹啉-2-酮类(IV_1～6)的结构经IR,¹HNMR,MS和HRMS确证;IV₃,IV₄和IV₆对兔主动脉环抑制作用较明显。结论化合物IV₃,IV₄和IV₆显示了一定的抑制活性,值得进一步研究。

Abstract: AIMTo study the synthesis and anti α-adrenoceptor activity of 1,2-dihydro-quinoline-2-one compounds. METHODSAcylation, bromination and cyclization, and substitute reactions were used in the synthesis of the title compounds IV. A proposed mechanism was showed to explain the unusual compounds 5 and 6 in the route C. The inhibition activity of the six target compounds were tested. RESULTSTwelve new compounds were synthesized (II_1～6 and IV_1～6). Among them, six new compounds (IV_1～6) are the title compounds. Structure of the title compounds were determined by IR, ¹HNMR, MS and HRMS. CONCLUSIONCompounds IV₃, IV₄ and IV₆ showed inhibiiton activity, and were worth further studying.