2,3 - Dihydro-quinoline -1 (1h) - Yl Acetic Acids And Quinoline -1 (1h) - Yl Acetic Acid-based Compound Design And Synthesis

The pathogenic mechanism of diabetic complications and the advances in the aldose reductase inhibitors (ARIs ) were briefly reviewed in this thesis.Many strong evidences show that an excessive accumulation of intracellular sorbitol from the sorbitol pathway activated under high glucose conditions is an important factor for the pathogenesis of diabetic complications, and ARIs can correct the abnormal condition of sorbitol pathway and decrease the sorbitol levels in body, so the long-term diabetic complications can be prevented or ameliorated.The aim of our study is to find novel ARIs with high activity and selectivity. Based on the structural features of carboxylic acids and chalcones with aldose reductase inhibitory activities and their action mechanisms on AR, (2,3-dihydro-quinolin-1(1H)-yl)acetic acids and (quinolin-1(1H)-yl)acetic acids were designed. Starting from ortho-substituted aniline, 15 target compounds were synthesized via Michael addition, hydrolysis, Friedel-Crafts, N-alkylation, and Claisen-Schimidt condensation. The structures of the compounds synthesized were confirmed by ~1H-NMR, UV and IR.