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 c...

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Veröffentlicht in:	Chemical & pharmaceutical bulletin 2013/04/01, Vol.61(4), pp.477-482
Hauptverfasser:	Lin, Kuaile, Cai, Zhengyan, Wang, Fei, Zhang, Wei, Zhou, Weicheng
Format:	Artikel
Sprache:	eng
Schlagworte:	Binding Sites Catalytic Domain Diabetes Mellitus, Type 2 - drug therapy dipeptidyl peptidase Dipeptidyl Peptidase 4 - chemistry Dipeptidyl Peptidase 4 - metabolism dipeptidyl peptidase 4 inhibitor Dipeptidyl-Peptidase IV Inhibitors - chemical synthesis Dipeptidyl-Peptidase IV Inhibitors - chemistry Dipeptidyl-Peptidase IV Inhibitors - therapeutic use Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - antagonists & inhibitors Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - metabolism Humans Molecular Docking Simulation Structure-Activity Relationship xanthine Xanthine - chemical synthesis Xanthine - chemistry Xanthine - therapeutic use
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Zusammenfassung:	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.
ISSN:	0009-2363 1347-5223
DOI:	10.1248/cpb.c12-01046