【作者】 王瑞雪；

【导师】 张运晓；

【作者基本信息】 郑州大学 ， 有机化学， 2012， 硕士

【摘要】 缓激肽B2受体拮抗剂作为一类能与人体内缓激肽B2受体作用的药物,对一些临床疾病如哮喘、胰腺炎、老年痴呆症、创伤性脑损伤、过敏性鼻炎、血管性水肿、骨关节炎等具有显著的疗效。自此类药物出现以来,得到了研究人员的广泛关注。近年来,一些课题组通过对缓激肽及其受体的深入研究,结合具体的药物构效关系,经过合理的设计,合成出很多具有良好生物活性的缓激肽B2受体拮抗剂分子,其中一些已进入临床试验阶段并取得了突破性的进展。针对缓激肽B2受体拮抗剂的研究与开发对人类的健康具有十分重要的意义。本文从以往研究人员针对此类药物的构效关系出发,结合日本Fujisawa制药公司的设计思路与合成方法,设计了两类非肽类缓激肽B2受体拮抗剂分子,并同时设计了合理的合成路线,对目标分子的合成方法进行了初步探索和优化。具体工作如下：以2,6-二氯甲苯为原料,经过F-C酰基化、酯化、溴代、取代、水解等一系列反应,合成了一系列新型B2受体拮抗剂候选化合物分子。同时对所设计的另一类拮抗剂分子进行了初步的合成探索。更多还原

【Abstract】 As a series of drugs that are able to effectively work on human Bradykinin B2Receptor, Bradykinin B2Receptor Antagonists have definite effect on some clinical diseases such as asthma, pancreatitis, Alzheimer’s Disease, traumatic brain injury, allergic rhinitis, angioedema, osteoarthritis, etc. Much more attentions have been paid to this kind of drugs since it was discovered. In recent years, some groups have designed and synthesized lots of Bradykinin B2Receptor Antagonists containing good biological activity through doing further research on the specific structure and activity relationship (SAR). Some novel antagonists have been used for clinical test and proved to be potential drugs. So it does make great sense for human health to do more study on the Bradykinin B2Receptor Antagonists.Based on the SAR of these kinds of drugs and great works that have been done by Fujisawa Pharmaceutical Co. Ltd., two kinds of non-peptide Bradykinin B2Receptor Antagonists were synthesized, and the synthetic route was explored and optimized. Specifically as follows: Beginning with2,6-dichlorotoluene, a series of B2Receptor Antagonists were synthesized through multi-step reactions, such as Fridel-Crafts acylation, esterification, bromination, substitution, hydrolysis and etc. Preliminary exploration for synthesis of another designed kind of Antagonists was already done.更多还原