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IBD (Inflammatory Bowel Diseases, IBD), including ulcerative colitis (Ulcerative Colitis, UC) and Crohn's disease (Crohn's Disease, CD), is a cause is not yet clear chronic non-specific inflammatory bowel disease. Increasing incidence of IBD trends, the most significant Western countries, North America and northern Europe, the highest incidence of IBD in recent years, the incidence of the disease in our country has significantly increased trend. Colorectal cancer is the fourth largest in the high incidence of cancer, and the annual rate of 5% rise, while UC is induced by one of the important factors of colorectal cancer, the possibility of malignant ulcerative colitis usually 3% to 5%. From this century, since the 1930s, sulfasalazine and 5-ASA has always been the main drug treatment of IBD. Recent studies show that 4-ASA in the treatment of IBD and 5-ASA has the same effect, but the site of action and mechanism have some differences, and the 4-ASA is effective in the treatment of active and non-active ulcerative colon inflammation, the 5-ASA, compared with fewer adverse reactions. However, direct oral administration of 4-ASA will soon be rapidly absorbed in the upper gastrointestinal tract, only a few reach the colon lesions play a therapeutic role. Design of this project reference to the 5-ASA-glu and 5-ASA-asp design principle, by a peptide bond to 4-ASA and the ligand linking the selected ligands including eleven acid, sorbic acid and α- linolenic acid. In this study, the first generation of unsaturated fatty acid anhydride and then with 4-ASA with the amino group on the benzene ring to increase with the 4-ASA reactive amino group on the benzene ring and yield; but of less linolenic acid product, and the price is more expensive, If the acid anhydride is formed first and then with 4-ASA reactive amino group on the phenyl ring can increase the reactivity though, but it reduces the yield of the resulting product. 4-ASA in the reaction directly with linolenic acid, 4-ASA because the carboxyl group and a phenolic hydroxyl group under the action of the DCC coupling with linolenic acid by-product formation. Therefore, the 4-ASA carboxyl and phenolic hydroxyl groups of the selective protection, selective removal by hydrogenation reduction method amino-protecting group, and the phase transfer catalyst, the reaction of the target product and linolenic acid. The topics explored two to 4-ASA and unsaturated fatty acids as raw material, through a peptide bond to combine the two together multi-step synthesis route, got three target product, and the synthesis of a new product with a melting point of destination , TLC, MS, FT-IR, 1H-NMR and 13C-NMR and other methods were characterized to determine their structure. For the synthesis of new efficiency and low toxicity of 4-ASA class of anti-inflammatory bowel disease drugs foundation. Theory needs practice test and calibration to continuous development and improvement. Therefore, in the new parent drug, new drugs and new ligand design principles of the compound synthesized under the direction of, whether the desired anti-UC verify the need for research activity. Pharmacodynamic study was to analyze and judge drugs against UC most direct and accurate method. The subject DNCB and acetic acid complexes were established mouse model of ulcerative colitis experiment is divided into normal control group (A), model group (B), 4 - amino acid azo derivatives of phenol treatment group ( C), positive drug (4-ASA) control group (D), in addition to group A, the other groups were back to DNCB-acetone liquid drops back sensitization daily, once a day for 14 consecutive days, the first 15 will be 0.3 % DNCB-ethanol solution 0.1ml poured into the colon, the 16th day of the same Act poured into 3% acetic acid 0.2ml. Group C and Group D enema dose of group C 100mg/kg/d, D group 200mg/kg/d, A, B groups were treated with corresponding volume of saline, administered from the day after modeling, a total of seven days, and finally with mouse disease activity index (DAI) and histopathological examination and treatment results. Through the above analysis of test results, when compared with the model group, the symptoms of treated mice and colonic mucosal tissue injury significantly improved (P lt; 0.01). 4 amino acid azo derivatives of phenols colitis in mice have a better therapeutic effect, but the mechanism remains to be further studied.
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