New 6-amino-pyrido[2,3-d]pyrimidine-2,4-diones as novel agents to treat type 2 diabetes: A simple and efficient synthesis, α-glucosidase inhibition, molecular modeling and kinetic study

A new series of 6-amino-pyrido[2,3-d]pyrimidine-2,4-dione derivatives 3a-3s were prepared via a facile and efficient reaction from alpha-azidochalcones and 6-amiouracils. The reactions were performed under mild conditions to produce the corresponding compounds in good to excellent yields. Obtained derivatives 3a-3s were evaluated for alpha-glucosidase inhibitory activity and all of them exhibited excellent in vitro yeast a-glucosidase inhibition with IC50 values ranging from 78.0 +/- 2.0 to 252.4 +/- 1.0 mu M. For example, the most active compound 3o was around 10-fold more potent than acarbose, a standard drug (IC50 = 750.0 +/- 1.5 mu M). Kinetic study of compound 3o revealed that it inhibited alpha-glucosidase in a competitive mode. Molecular modeling studies of the most active compounds 3o, 3i, 3e and 3m were also performed. (C) 2018 Elsevier Masson SAS. All rights reserved.