Synthesis,biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors |
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| Institution: | 1. School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal (MP) 462036, India;2. Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark;3. Protein Phosphorylation and Human Disease Group, USR3151, Station Biologique, B.P. 74, 29682 Roscoff cedex, Bretagne, France;4. ManRos Therapeutics, Centre de Perharidy, 29680 Roscoff, Bretagne, France;1. Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave., Room E504, Indianapolis, IN 46202, USA;2. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA;3. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Dr, West Lafayette, IN 47907, USA;1. Institute for Neurodegenerative Diseases, University of California, San Francisco, United States;2. Department of Neurology, University of California, San Francisco, United States;3. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, United States;4. Small Molecule Discovery Center, University of California, San Francisco, United States;5. Department of Pharmaceutical Chemistry, University of California, San Francisco, United States;1. Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India;2. Department of Pharmaceutical Sciences, Assam University, Silchar 788 011, India;3. National Toxicology Centre, Vadgaon Khurd, Sinhagad Road, Pune 411 041, India;1. Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA;2. Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, USA;1. Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221 005, India;2. National Toxicology Centre, Vadgaon Khurd, Sinhagad Road, Pune, 411 041, India |
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| Abstract: | A series of novel 4-anilinoquinazoline derivatives (3a–3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer’s disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3α/β kinase with IC50 values of 1.5 μM and 3 μM, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3β. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3α/β enzymes with potential therapeutic application in Alzheimer’s disease. |
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| Keywords: | Anilino quinazolines Protein kinase inhibitor CLK1 kinase Docking studies |
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