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Design, synthesis and computational validation of novel benzimidazole/indole-based PPARα and PPARγ partial agonists

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Abstract

The design and synthesis of benzimidazolyl and indolyl linked α-alkoxy phenylpropanoic acid derivatives and the β-keto ester analogues in an effort to develop novel peroxisome proliferator activated receptors ligands expected to exhibit PPARα and PPARγ partial agonism in the management of hyperglycemia and hyperlipidemia for the treatment of type 2 diabetes is reported. Computational validation of the designed molecules through activity prediction and docking studies showed expected results.

Syntheses of benzimidazole and indole linked benzyl based α-alkoxy propanoic acids and benzylidene and benzyl based β-ketoesters, as partial PPARα/γ agonists as Anti Type 2 Diabetic compounds, followed by their activity and binding affinity prediction at individual PPARs to support the design of the molecules with expected partial agonism, are reported.

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Acknowledgements

The authors are thankful to Head, Department of Chemistry, Punjabi University and are also grateful to the Director, Regional Sophisticated Instrumentation Centre (RSIC), Panjab University, Chandigarh and Director, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab for extending the facilities for the analysis of various compounds reported in this paper. We greatly acknowledge the financial support from IndSwift Labs. Ltd., SAS Nagar, Mohali, Punjab for the ISLL-Punjabi University Collaborative Research Project, and providing the research fellowship to two of the authors VK and PG and for the timely guidance and support.

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Authors and Affiliations

  1. Synthetic Organic and Medicinal Chemistry Laboratory, Department of Chemistry, Punjabi University, Patiala, 147 002, India

    RAMAN K VERMA, PRITHWISH GHOSH & VIJAY KUMAR

  2. Ind-Swift Laboratories Limited (Research and Development Centre), Plot No. E-5, Industrial Area, Phase-2, SAS Nagar, Mohali, 160 055, India

    LALIT K WADHWA

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  1. RAMAN K VERMA
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  2. PRITHWISH GHOSH
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Correspondence to RAMAN K VERMA.

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VERMA, R.K., GHOSH, P., KUMAR, V. et al. Design, synthesis and computational validation of novel benzimidazole/indole-based PPARα and PPARγ partial agonists. J Chem Sci 125, 1555–1571 (2013). https://doi.org/10.1007/s12039-013-0489-4

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  • DOI: https://doi.org/10.1007/s12039-013-0489-4

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