title: Synthesis, Docking Study and Kinase Inhibitory Activity of a Number of New Substituted Pyrazolo[3,4-c]pyridines.
abstract: A series of new pyrazolo[3,4-c]pyridines bearing various 1, 3, 5 or 1, 3, 7 pattern substitutions, were designed and synthesized. Some of them showed interesting inhibitory activity mainly against glycogen synthase kinase 3 (GSK3)α/β as well as against cdc2-like kinases 1 (CLK1) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), with good selectivity and remarkable structure-activity relationships (SARs), without being cytotoxic. Molecular simulations in correlation with biological data revealed the importance of the existence of N1-H as well as the absence of a bulky 7-substituent.
authors.affiliation: School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens.
authors.forename: Meropi
authors.initials: M
authors.lastname: Sklepari
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Lougiakis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papastathopoulos
authors.forename: Nicole
authors.initials: N
authors.lastname: Pouli
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Marakos
authors.forename: Vassilios
authors.initials: V
authors.lastname: Myrianthopoulos
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bach
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mikros
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ruchaud
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D062105:Molecular Docking Simulation; 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; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000097603:Dyrk Kinases
chemical_list: D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011720:Pyrazoles; D011725:Pyridines; D000097603:Dyrk Kinases; C447480:pyrazolo(3,4-b)pyridine; C066780:Clk dual-specificity kinases