Novel synthesis of dihydropyrimidines for alpha-glucosidase inhibition to treat type 2 diabetes: In vitro biological evaluation and in silico docking

作者：Yar Muhammad^*; Bajda Marek; Shahzadi Lubna; Shahzad Sohail Anjum; Ahmed Maqsood; Ashraf Muhammad; Alam Umber; Khan Islam Ullah; Khan Ather Farooq

来源：Bioorganic Chemistry, 2014, 54: 96-104.

DOI：10.1016/j.bioorg.2014.05.003

• alpha-Glucosidase inhibitors
• Dihydropyrimidine
• Biginelli reaction
• N-acetyl glycine
• Acarbose

A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against alpha-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC50 value 112.21 +/- 0.97 mu M), to show the enzyme - inhibitor interactions.

• 出版日期2014-6