王沥王沥研究【参考】.doc

摘 要 近年来，随着我国社会经济的发展，人们生活水平的提高，以及人口老龄化进程的加快，心血管疾病的发病率明显上升，发病年龄也有所提前，它已成为当今人类所面临的重要健康问题。血栓性疾病是一种常见的心血管疾病由血栓形成和血栓栓塞引起体外、因此F16618之前的抗血栓药物药效F16618结构中的多个不饱和基团及缺电子的迈克尔受体设计并合成一系列联苯骨架化合物化合物与F16618，有望保留F16618的生物活性的合成方法合成的化合物通过薄层(TLC)和快速柱层析法(FC)、重结晶分离提纯，通过高效液相色谱法(HPLC)核磁共振(NMR)、液质联用技术(LC-MS)等方法结构鉴定目标化合物结构的确性。Abstract In recent years, the incidence of cardiovascular disease is increasing in our country with the development of social economy, the improvement of peoples living standards, and the acceleration of the process of aging population, the age of onset is also getting younger, it has become an important health issue that humanity facing today. Thrombotic disease is a kind of common disease of cardiovascular system, it is caused by thrombosis and thromboembolism. Currently antithrombotic drugs include Aspirin and Plavix, but they have limited efficacy and adverse reaction of bleeding, which greatly limits the scope of application of the drugs. In 1991, Professor Coughlin’s team found and cloned the thrombin receptor of platelet, which provided a new target for the study of antithrombotic drugs. Since then thrombin receptor antagonist has become a hot spot in the research of antithrombotic drugs. F16618 is a new type of simple and small molecule PAR-1 antagonist developed by the Fabre Pierre research center in France, which has a good antithrombotic activity in vitro and in vivo and no increase of bleeding. Therefore, F16618 may have better properties than previous drugs. We have designed and synthesized a series of new structures, which are based on our earlier research on F16618 analogues which are structure optimization of electron deficient unsaturated groups. The structures of these compounds are similar to F16618, the synthesis route is simple, and it is expected to reduce side effect and retain the biological activity of F16618. We use simple, efficient, environmentally friendly, and economical modern organic synthesis method to synthesize these new compounds. A t