title: Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors.
abstract: The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC(50) (microM) DYRK1A=11; CDK5=0.41; GSK-3=1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer's disease.
authors.affiliation: Laboratorio de Radicales Libres y Química Computacional (IQOG, CSIC), 28006 Madrid, Spain.
authors.forename: Mourad
authors.initials: M
authors.lastname: Chioua
authors.forename: Abdelouahid
authors.initials: A
authors.lastname: Samadi
authors.forename: Elena
authors.initials: E
authors.lastname: Soriano
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: José
authors.initials: J
authors.lastname: Marco-Contelles
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D001665:Binding Sites; D003198:Computer Simulation; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; 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; D000097603:Dyrk Kinases
chemical_list: D051360:Cyclin-Dependent Kinase 5; D038362:Glycogen Synthase Kinase 3; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011720:Pyrazoles; D011725:Pyridines; D000097603:Dyrk Kinases; C543937:3,6-diamino-1H-pyrazolo(3,4-b)pyridine