Stereoselective synthesis and in-silico evaluation of C4-benzimidazolyloxyphenyl substituted trans-β-lactam derivatives as promising novel PPARγ activators

Abstract

A convenient and stereoselective synthesis of a novel series of C4-benzimidazolyloxyphenyl substituted trans-β-lactam derivatives is described. The scope of the reaction was examined by varying different aromatic and aliphatic functionalities on ketene and imine viz. –Cl, –SC₆H₅, –SeC₆H₅, –OCH₃, –C₆H₄.Cl(p), –C₆H₄.OCH₃(p) and –CH₂C₆H₅. All compounds were characterized on the basis of various spectroscopic techniques (FT-IR, ¹H NMR, ¹³C NMR, elemental and mass analysis). The trans- or cis-configuration of β-lactams (4, 5) was assigned with respect to the relative position of C3-H and C4-H. The molecular docking studies were performed between representative compounds and PPARγ receptors which revealed that functionality at N1 significantly affects the binding affinity of the compounds in comparison to functionality at C3 of β-lactam unit. The in-silico studies lead to the identification of β-lactam 4a as potential candidate for development of future antidiabetic agents.

Graphical Abstract

Keywords:

• Antidiabetic
• benzimidazole
• β-lactam
• molecular docking
• PPAR
• stereoselective

Acknowledgments

We acknowledge the Sophisticated Analytical Instrumentation Facility (SAIF), Panjab University, Chandigarh, India.

Additional information

Funding

JB acknowledge the financial support from University Grants Commission (UGC) New Delhi, Government of India, vide sanction [No. F.17-7(J)/2004 (SA-I)] dated 03-10-2011. AB gratefully acknowledges the financial support for this work from Department of Science and Technology (DST), New Delhi, Government of India, Project [No. SR/FT/CS-037/2010] dated 28-10-2010.