title: Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors.
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.
authors: School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal (MP) 462036, India.
authors: Digambar Kumar
authors: DK
authors: Waiker
authors: School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal (MP) 462036, India.
authors: Chandrabose
authors: C
authors: Karthikeyan
authors: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
authors: Vasanthanathan
authors: V
authors: Poongavanam
authors: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
authors: Jacob
authors: J
authors: Kongsted
authors: Protein Phosphorylation and Human Disease Group, USR3151, Station Biologique, B.P. 74, 29682 Roscoff cedex, Bretagne, France.
authors: Olivier
authors: O
authors: Lozach
authors: Protein Phosphorylation and Human Disease Group, USR3151, Station Biologique, B.P. 74, 29682 Roscoff cedex, Bretagne, France; ManRos Therapeutics, Centre de Perharidy, 29680 Roscoff, Bretagne, France.
authors: Laurent
authors: L
authors: Meijer
authors: School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal (MP) 462036, India. Electronic address: piyush.trivedi@rgtu.net.
authors: Piyush
authors: P
authors: Trivedi
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3
keywords: Anilino quinazolines; CLK1 kinase; Docking studies; Protein kinase inhibitor