Author(s):
Gourav Jain, Neha Kawathekar
Email(s):
gourav.4484jain@gmail.com
DOI:
10.52711/0974-360X.2025.00720 
Address:
Gourav Jain*, Neha Kawathekar
Department of Pharmacy, Shri Govindram Seksariya Institute of Technology and Science, 23-Park Road, M. Vishweshraiya Marg, Indore-452003, Madhya Pradesh, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 10,
Year - 2025
ABSTRACT:
4-Nitro-N-(piperidin-4-yl)benzamide (S5I2) is a key pharmacophore for GPR119 agonists, promoting insulin secretion and incretin release without causing hypoglycemia. Its structural design enhances receptor binding, bioavailability, and glucose regulation, making it a promising candidate for diabetes treatment. A series of derivatives (S5F1-S5F7) was synthesized through a two-step process. Initially, 4-nitrobenzoic acid (1) reacted with tert-butyl 4-aminopiperidine-1-carboxylate (2) to form intermediate-1, S5I1, which was then deprotected using TFA to yield intermediate-2, S5I2. The final compounds were synthesized via amidation coupling with substituted benzoic and nicotinic acids/chlorides using 1-Ethyl-3- (3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), Hydroxybenzotriazole (HOBT)/ Hexafluorophosphate aza benzotriazole tetramethyl uronium (HATU), Triethylamine (TEA), and Dimethylformamide (DMF). Molecular docking (AutoDock 4.0) evaluated ligand interactions with the GPR119 receptor, designed through homology modeling (MODELLER). SwissADME software was used to assess pharmacokinetic properties. Docking results identified S5F4 and S5F2 showed the best binding affinity (-12.8) and (-10.7) respectively in comparison to reference molecule AR231453 with (-11) and emerged as potent ligands. The integration of fluorine atoms in S5F4, owing to their high electronegativity and small size, can strengthen receptor binding affinity and optimize pharmacokinetic properties. Structural confirmation and validation of synthesized compounds were achieved through FT-IR, 1H/13C NMR, and LC-MS.
Cite this article:
Gourav Jain, Neha Kawathekar. Synthesis, characterization and In-silico study of some 4-nitro-N-(piperidin-4-yl)benzamide derivatives as GPR119 agonists for the treatment of diabetes. Research Journal of Pharmacy and Technology. 2025;18(10):4981-9. doi: 10.52711/0974-360X.2025.00720
Cite(Electronic):
Gourav Jain, Neha Kawathekar. Synthesis, characterization and In-silico study of some 4-nitro-N-(piperidin-4-yl)benzamide derivatives as GPR119 agonists for the treatment of diabetes. Research Journal of Pharmacy and Technology. 2025;18(10):4981-9. doi: 10.52711/0974-360X.2025.00720 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-10-59
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