替米沙坦及其类似物的合成和生物活性研究  

Synthesis of Telmisartan and Its Derivatives and Evaluation of Their Biological Activities

作　　者：余伟发[1] 周智明[1] 朱海波[2] 何令帅[2] 

机构地区：[1]北京理工大学新药研究开发中心 [2]中国医学科学院中国协和医科大学药物研究所,北京100050

出　　处：《有机化学》2006年第3期318-323,共6页Chinese Journal of Organic Chemistry

摘　　要：设计合成了替米沙坦及其类似物,改进了替米沙坦的合成工艺.用邻苯二胺与相应的有机羧酸缩合,所得产物苯并咪唑衍生物与4'-溴甲基联苯-2-甲酸甲酯通过N-烷基化得到相应的目标化合物,合成了替米沙坦和9种未见文献报道的苯并咪唑联苯化合物,其结构经1HNMR,IR,MS和元素分析确证.用体外动脉环的方法,研究目标化合物的初步体外抗高血压活性,试验结果表明其中部分化合物具有一定的抗高血压活性.The synthetic route of telmisartan and its derivatives was developed and improved. The condensation of o-phenylenediamine with various carboxylic acids gave benzimidazole derivatives, which were N-alkylated with methyl 4＇-（bromomethyl）biphenyl-2-carboxylate to afford the corresponding title compounds. Nine novel title compounds were synthesized, and their structures were confirmed by ^1H NMR, IR, MS spectra and elemental analyses. And the in vitro preliminary antihypertensive activity was evaluated by the method of aortic ring. Biological screening results demonstrated that some of the compounds displayed potential antihypertensive activity.

关 键 词：非肽类血管紧张素Ⅱ受体拮抗剂 替米沙坦 合成 衍生物 生物活性 

分 类 号：TQ463.53[化学工程—制药化工]