Microwave-assisted synthesis of bioactive tetrahydropyrimidine derivatives as antidiabetic agents

Abstract

Introduction: In drug discovery, pyrimidine analogues show good biological response and many drug moieties have pyrimidine core. Aim: On the basis of prior review, we synthesized a series of N-(substituted phenyl)-1,3,6-trimethyl-4-(4-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)methoxy)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide parade a 1,3,4-oxadiazole core which were evaluated for in vitro antidiabetic screening. Materials and methods: The tetrahydropyrimidine derivatives have been synthesized by microwave irradiation method. It was carried out by Biginelli condensation of 1,3,4-oxadiazole based aldehyde, substituted acetoacetanilide and N,N’-dimethyl urea. All synthesized compounds were evaluated for antidiabetic screening. Results: By the results derived from antidiabetic activity, compounds 4a, 4e, 4g, and 4i show good inhibition compared to others because of electron withdrawing and hydroxyl groups. All results are compared with standard drug acarbose. Conclusions: In conclusion, a series of 1,3,4-oxadizole bearing tetrahydropyrimidine has been synthesized and evaluated for in vitro antidiabetic screening. The derivatives 4a, 4e, 4g, and 4i exhibited promising antidiabetic activity.

Advancement in chiral heterocycles for the antidiabetic activity

“…As shown in Figure 2, the synthesis of chiral heterocycles, methyl-2-(6-hydroxybenzofuran-3-yl) acetate with remarkable enantioselectivities and coworkers synthesized one compound, namely TAK-875. 26 When the equivalent benzofuran was converted into a chiral intermediate, 27 TAK-875 was generated with 97% yield F I G U R E 1 US-FDA approved clinical chiral heterocyclic molecules as antidiabetic drugs.…”

“…As shown in Figure 2, the synthesis of chiral heterocycles, methyl‐2‐(6‐hydroxybenzofuran‐3‐yl) acetate with remarkable enantioselectivities and coworkers synthesized one compound, namely TAK‐875 26 . When the equivalent benzofuran was converted into a chiral intermediate, 27 TAK‐875 was generated with 97% yield and 93% enantiomeric excess by reacting with 2′,6′‐Dimethyl‐4′‐[3‐(methylsulfonyl) propoxy] biphenyl‐3‐yl methanol 28 .…”