Discovery of novel dihydro-pyrimidine hybrids: insight into the design, synthesis, biological evaluation and absorption, distribution, metabolism and excretion studies

Aim: By keeping in aspects, the pharmacological potential of heterocyclic compounds, pyrimidine-based compounds were designed, synthesized and evaluated for α-amylase inhibitory potential.Materials & methods: Five new series 1a-l, 2a-d, 3a-d, 4a-d and 5a-d of 1,2,3,4-tetrahydroprimidine-5-carboxylate derivatives were designed by de novo method by taking Alogliptin as reference compound. Here in we describe synthesis and characterization of compounds as potential α-amylase inhibitor.Results: Structure activity relationship (SAR), in vitro analysis and molecular modelling approaches generate compounds 1 h, 1i, 1k and 4c as potential lead with good α-amylase inhibitory selection. However, compound 1k failed the criteria of optimization as drug lead by ADME studies while all Other compounds showed optimum range for all in silico ADME parameters.Conclusion: Therefore, these compounds can serve as potential lead candidate in developing anti-diabetic therapy.

alogliptin; hyperosmolar hyperglycemic syndrome (HHS); pharmacophore; voglibose; α-amylase inhibition.