替米沙坦及其氰基类似物的合成与生物活性研究.pdfVIP

替米沙坦及其氰基类似物的合成和生物活性研究 1 1 ,2 1 3 3 薛为哲 , 余伟发 , 周智明* , 朱海波 , 何令帅 (1. 北京理工大学新药研究开发中心 , 北京 100081 ; 2. 中国石化股份有限公司石油化工 科学研究院 , 北京 100083 ; 3. 中国医学科学院中国协和医科大学药物研究所 , 北京 100050) 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-氰基通过N-烷基化得到相应的 目标化合物, 合成了替米沙坦和8 种未见文献报道的苯并咪唑联苯化合物, 其结构经 1H-NMR, 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. 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 Synthesis of Telmisartan and Its Derivatives and Evaluation of Their Biological Activities 1 1 ,2 1 3 3 Xue Wei-zhe , YU Wei-fa ,ZHOU Zhi-ming * , ZHU Hai-bo , HE Ling-shuai (1. Research Development Center for Pharmaceuticals, Beijing Institute of Technology, Beijing 100081 ; 2. Research Institute of Petroleum Processing, China Petroleum Chemical Corporation, Beijing 100083 ; 3. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050) Abstract 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-nitrile to afford the corresponding title compounds. Eight 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. Keywords angiotensin II receptor antagonist; telmisartan; synthesis; derivative; bioactivity 替米沙坦(1)[1] (4-{4- 甲基-6-(1- 甲基 有相似性, 经过筛选也可发现先导化合物. -1H- 苯