Development of new types of aldose reductase inhibitors based on the structure of the target enzyme

2015 Fiscal Year Final Research Report

• Project/Area Number: 25410179
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Toho University
• Principal Investigator: SAITO Ryota 東邦大学, 理学部, 准教授 (90327974)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アルドース還元酵素阻害剤 / ドッキングスタディ / ピラジン / プテリン / GFP発色団モデル

Outline of Final Research Achievements

Aldose reductase (ALR2) is associated with the onset of diabetic complications, and therefore ALR2 inhibitors has attracted attentions of medicinal chemists. Despite numerous devotions of the researchers, only one drug, epalrestat, has been launched on the market, and accordingly the development of new candidates for ALR2 inhibitors is still desired. The present work revealed that botryllazine B analogues possessing diverse substituted phenylcarbonyl groups on the 2-position and various fused bicyclic aromatic systems on the 6-position, pterin-7-carboxamides, and (Z)-4-arylmethylidene-1H-imidazol-5(4H)-ones (GFP chromophore model compounds) are highly potent ALR2 inhibitors. Docking simulations of these compounds also revealed that each of them exhibited specific interaction with ALR2. In conclusion, the compounds synthesized in this study have proved to be potential drugs for diabetic complications.

Free Research Field

複素環化学