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

摘要

A new series of 6-amino-pyrido[2,3-d]pyrimidine-2,4-dione derivatives3a–3swere preparedviaa facile and efficient reaction fromα-azidochalcones and 6-amiouracils. The reactions were performed under mild conditions to produce the corresponding compounds in good to excellent yields. Obtained derivatives3a–3swere evaluated for α-glucosidase inhibitory activity and all of them exhibited excellentin?vitroyeastα-glucosidase inhibition with IC50values ranging from 78.0?±?2.0 to 252.4?±?1.0?μM. For example, the most active compound3owas around 10-fold more potent than acarbose, a standard drug (IC50?=?750.0?±?1.5?μM). Kinetic study of compound3orevealed that it inhibitedα-glucosidase in a competitive mode. Molecular modeling studies of the most active compounds3o,3i,3eand3mwere also performed.