【作者】 郭璟；

【导师】 赵正保；

【作者基本信息】 山西医科大学 ， 药物化学， 2004， 硕士

【摘要】 炎性肠病（inflammatory bowel diseases,IBD）包括溃疡性结肠炎（ulcerative colitis,UC）和克隆病（Crohn’s Disease,CD），是一组发病机理不明的慢性肠道炎症性疾病。在欧美国家发病率较高，近年来亚洲国家的发病率也逐渐升高。柳氮磺胺吡啶（Sulfusalazine,SASP）和5-氨基水杨酸（5-aminosalicylic acid,5-ASA）一直以来都是治疗IBD的主要药物。近年来有研究表明4-ASA在IBD的治疗上与5-ASA有同样高的疗效。但是直接口服的4-ASA很快就会在小肠上段吸收，只有少量能到达结肠发挥治疗作用，因此研究一种结肠特定性的4-ASA前体药物是很有必要的。体外试验表明，5-氨基水杨酸（5-ASA-Gly）可作为5-ASA结肠特定性给药的前体药物，基于4-ASA是5-ASA的同分异构体，而且化学结构相似，所以可以选择甘氨酸作为4-ASA结肠特定性前体药物的载体。本文探索了一条4-ASA衍生物—4-ASA-Gly的多步合成工艺，得到了目标产物4-ASA-Gly和五个中间体产物，对合成的目标产物和中间产物用熔点、薄层色谱、FT-IR、¹H-NMR和¹³C-NMR进行了详细的表征，给出了它们的结构。本课题的研究工作为合成新型的高效低毒4-ASA类抗炎性肠病药物奠定了基础。更多还原

【Abstract】 Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease, which have been popular among Europeans and Americans, are now getting increased in Asian countries such as Japan, Korea, and China since the end of the 1990’s. The exact etiology of the IBD is not yet clearly understood. For many years, sulphasalazine (SASP) and 5-aminosalicylic acid(S-ASA) have been used in the treatment of IBD. Recently, 4-ASA has been reported as highly effective as 5-ASA in the maintenance treatment of IBD. But after oral ingestion uncoated 4-ASA is rapidly absorbed in the upper intestinal tract. So delivery of orally administered 4-ASA specifically to the colon is highly desirable. Results from in vitro experiments suggested that 5-ASA-Gly is a colon-specific prodrug of 5-ASA. As 4-ASA is an isomer of 5-ASA and they have the similar structure, glycine can be choosed as a colon-specific carrier. In this paper, we investigated the synthetic route in the conjugating reaction of glycine and 4-ASA, and five intermediates have been prepared. We characterized their structures. They are characterized by melting point, TLC, FT-IR, ’H-NMR and 13C-NMR spectra properties in details. Their structures are given out. By our studying, we have provided a suitable synthesis route for further exploring new compounds in the treatment of IBD.更多还原