Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis,SAR study,and biological activity |
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| Affiliation: | 1. Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China;2. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China;3. High Magnetic Field Laboratory, Chinese Academy of Sciences, P.O. Box 1110, Hefei, Anhui 230031, PR China;4. University of Science and Technology of China, Hefei, Anhui 230036, PR China;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt;2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;3. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China;2. Department of Medicinal Chemistry, Nanjing Sanhome Pharmaceutical Co., Ltd, Nanjing 210018, PR China;3. Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China;1. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China;2. Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;3. CAS Key Laboratory of Receptor Research, Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;1. School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China;2. Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China |
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| Abstract: | Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7 g exhibited the most inhibitory activity against c-Met with IC50 of 53.4 nM and 253 nM in enzymatic and cellular level, respectively. Following that, the compound 7 g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7 g was a potential c-Met inhibitor deserving further investigation for cancer treatment. |
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| Keywords: | c-Met kinase inhibitors Cancer Molecular docking Imidazopyridine derivatives |
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