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Synthesis and Evaluation of Thiouracil Derivatives as Dipeptidyl Peptidase IV Inhibitors
Author(s) -
Sharma Mani,
Singh Divya,
Gupta Monica
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12070
Subject(s) - thiouracil , dipeptidyl peptidase , chemistry , piperazine , enzyme , dipeptidyl peptidase 4 , acetamide , biochemistry , pharmacology , thyroid , diabetes mellitus , organic chemistry , endocrinology , biology , type 2 diabetes
A series of thiouracil derivatives were designed, synthesized and screened for in vitro inhibition of dipeptidyl peptidase IV. The SAR study indicated the influence of substituted chemical modifications on thiouracil scaffold. Compounds 8 (IC 50 = 0.32 μ m ), 9 (IC 50 = 0.29 μ m ), and 12 (IC 50 = 0.25 μ m ) showed excellent dipeptidyl peptidase IV inhibition having heterocyclic substituted piperazine with acetamide linker resulted as most potent dipeptidyl peptidase IV inhibitors among all the compounds screened. Single dose (10 mg/kg) of the compounds 8 , 9 , and 12 significantly reduced glucose excursion during oral glucose tolerance test in streptozotocin‐induced diabetic rat model. The present study on substituted thiouracil derivatives shows good‐to‐moderate inhibitory potential of dipeptidyl peptidase IV enzyme.