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 alpha-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 alpha-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 alpha-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.