Lin Kuaile, Cai Zhengyan, Wang Fei, Zhang Wei, Zhou Weicheng
State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives, Shanghai Institute of Pharmaceutical Industry, State Institute of Pharmaceutical Industry, Shanghai, China.
Chem Pharm Bull (Tokyo). 2013;61(4):477-82. doi: 10.1248/cpb.c12-01046. Epub 2013 Jan 28.
A series of xanthine derivatives in which a methylene was inserted at position 8 of xanthine scaffold was synthesized and evaluated as inhibitors of dipeptidyl peptidase 4 (DPP-4) for the treatment of type 2 diabetes. As the results of structure-activity relationship (SAR) study of the series, the compounds with 4-methyl-quinazoline-2-yl-methyl group at N-1 position and 2-aminoethylaminomethyl group gave better activities. Compounds H4 and H9 showed good DPP-4 inhibition and more than 100-fold selectivity over DPP-7 and DPP-8.
合成了一系列在黄嘌呤骨架的8位插入亚甲基的黄嘌呤衍生物，并将其作为二肽基肽酶4（DPP-4）抑制剂进行评估，用于治疗2型糖尿病。作为该系列构效关系（SAR）研究的结果，在N-1位带有4-甲基喹唑啉-2-基甲基和2-氨基乙氨基甲基的化合物具有更好的活性。化合物H4和H9表现出良好的DPP-4抑制活性，对DPP-7和DPP-8的选择性超过100倍。
