Synthesis and biological evaluation of xanthine derivatives on dipeptidyl peptidase 4.
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.
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.
Kuaile
K
Lin
Zhengyan
Z
Cai
Fei
F
Wang
Wei
W
Zhang
Weicheng
W
Zhou
D001665:Binding Sites; D020134:Catalytic Domain; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D019820:Xanthine / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; D019820:Xanthine; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II; D018819:Dipeptidyl Peptidase 4