Design and Synthesis of Benzimidazole-Linked meta-Substituted Benzylidenes/Benzyls as Biologically Significant New Chemical Entities

Abstract

meta-Linked thiazolidinedione (TZD)– and diethyl malonate (DEM)–based benzylidenes and methyl acetoacetate (MAA)–based benzyl moieties linked to the 2-position of N-methyl benzimidazole were synthesized. TZD- and DEM-based compounds were synthesized by condensation of 2,4-thiazolidinedone and DEM respectively with the corresponding 3-substituted benzaldehyde, whereas MAA-based compounds were obtained by halogen displacement with the corresponding 3-substituted phenol. These new chemical entities were designed to provide a balanced agonism at the peroxisome proliferator activated receptor alpha/gamma (PPARα/γ) in the management of type 2 diabetes: a move from glitazones to selective PPARγ modulators (SPPARγMs).

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

GRAPHICAL ABSTRACT

Keywords:

• Benzimidazole
• benzylidene
• diethylmalonate
• methyl acetoacetate
• 2,4-thiazolidinedione

ACKNOWLEDGMENTS

We are thankful to the Punjabi University authorities for providing the necessary research facilities. We are also grateful to the director and Avtar Singh of RSIC, Panjab University, Chandigarh, and director, NIPER, SAS Nagar, Mohali, Punjab, for extending the facilities for spectral analysis of the compounds reported in this article. One of the authors (R.M.) is thankful to the Ministry of Social Justice and Empowerment, government of India, for providing a research fellowship.

Notes

^a Gold score^{[ 25 ]} of the best docked conformation.

^b The code written is as given in the reference.

Notes. db, double bond; sb, single bond.