Design and synthesis of quinazoline-3,4-(4H)-diamine endowed with thiazoline moiety as new class for DPP-4 and DPPH inhibitor |
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| Institution: | 1. Department of Medicinal Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, United States;2. Department of Structural Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, United States;3. In Vitro Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, United States;4. In Vivo Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Rd., Kenilworth, NJ 07033, United States;1. Division of Metabolism, Department of Internal Medicine, China Medical University, Taichung 40402, Taiwan;2. School of Pharmacy, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan;3. Ph.D. Program for Biotech Pharmaceutical Industry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan;4. Institute of New Drug Development, China Medical University, No. 91 Hsueh-Shih Rd., Taichung 40402, Taiwan;5. Master Program for Pharmaceutical Manufacture, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan;6. Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan;7. Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 41354, Taiwan;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research—Ahmedabad, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India;2. Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India;3. Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India;1. Key Laboratory of Small Fuctional Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China;2. Key Laboratory of Green Chemistry, Jiangxi Province, Nanchang, Jiangxi 330022, China;1. Programa de Maestría y Doctorado en Ciencias Químicas, UNAM, México, DF 04510, Mexico;2. Facultad de Química, Departamento de Farmacia, UNAM, México, DF 04510, Mexico;3. Escuela Superior de Medicina, Laboratorio de Modelado Molecular y Bioinformática de la SEPI, IPN, México, DF 11340, Mexico;4. Escuela Nacional de Ciencias Biológicas, Departamento de Parasitología, IPN, México, DF 11340, Mexico;5. Departamento de Infectología, Instituto Nacional de Perinatología, México, DF 11000, Mexico;6. Tecsiquim S.A. de C.V., Toluca Estado de México 50233, Mexico;1. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China;2. Department of Radiology, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53705, USA |
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| Abstract: | New N3-benzylidene (substituted)-2-phenyl-N4-(thiazol-2-yl)-quinazoline-3,4-(4H)-diamine derivatives were design and synthesized by a sequence of reactions starting from appropriate 6-methyl anthranilic acid. The title compounds were screened for in vitro dipeptidyl peptidase IV (DPP-4) inhibitory activity and diphenyl-2-picryl-hydrazyl (DPPH) assay and results showed significant to good activity in compared to Linagliptin for antidiabetic activity and Ascorbic acid for antioxidant activity. Compound 7g (IC50 = 0.76 nM) exhibited most promising DPP-4 inhibitory activity and also showed good antioxid and result. Docking study was also performed to provide an insight about the binding mode into binding sites of DPP-4 enzyme. Hopefully in future, compound 7g could be used as a lead compound for developing new antidiabetic agent with good antioxidant property. |
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| Keywords: | Quinazoline Thiazoline DPP-4 inhibitors DPPH Molecular docking |
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