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Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Pyrazoline scaffold: hit identification to lead synthesis and biological evaluation as antidiabetic agents
Shweta Sharma1,2, Mohd Hafizur Rehman Ansari3, Kalicharan Sharma
1Department of Pharmaceutical Chemistry, Drug Design & Medicinal Chemistry Lab, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India.
Abstract:
Background: Mining of novel scaffolds as potential DPP-IV inhibitors for future development of potential candidates as antidiabetic agents to address global issues. Methodology: The identified hit KB-10 from a previously reported study was taken as a lead for designing a library of analogues and screened initially based on in silico parameters and docking score. A series of selected (2[4-(1-acetyl-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenoxy]-1-phenylethanone derivatives were synthesized and evaluated through in vitro studies. Compounds KB-23, KB-22 and KB-06 were found to be as potent, with IC50 values of 0.10 μM, 0.12 μM and 0.35 μM, respectively. They also showed promising antihyperglycemic potential in in vivo studies (oral glucose tolerance tests) in Wistar rats. Conclusion: This work establishes pyrazoline analogues KB-23, KB-22 and KB-06 as promising starting points for the development of potential antidiabetic agents.
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