Τίτλος:
Synthesis, docking study and kinase inhibitory activity of a number of new substituted pyrazolo[3,4-c]pyridines
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2017 The Pharmaceutical Society of Japan.
Συγγραφείς:
Sklepari, M.
Lougiakis, N.
Papastathopoulos, A.
Pouli, N.
Marakos, P.
Myrianthopoulos, V.
Robert, T.
Bach, S.
Mikros, E.
Ruchaud, S.
Περιοδικό:
Chemical and Pharmaceutical Bulletin
Εκδότης:
Pharmaceutical Society of Japan
Λέξεις-κλειδιά:
2 (4 methylpiperazin 1 yl) n (5 (phenylamino) 1h pyrazolo[3,4 c]pyridin 3 yl)acetamide; 2 (dimethylamino) n (5 (phenylamino) 1h pyrazolo[3,4 c]pyridin 3 yl)acetamide; 2 (phenylamino) n (5 (phenylamino) 1h pyrazolo[3,4 c]pyridin 3 yl)acetamide; casein kinase I; cdc2 like kinase 1; cdc2 like kinase 2; cyclin dependent kinase 5; dual specificity phosphatase; dual specificity tyrosine phosphorylation regulated kinase 1a; glycogen synthase kinase 3; haspin protein; n (5 (cyclohexylamino) 1h pyrazolo[3,4 c]pyridin 3 yl) 2 (4 methylpiperazin t yl)acetamide; n (5 (cyclohexylamino) 1h pyrazolo[3,4 c]pyridin 3 yl) 2 (dimethylamino)acetamide; n (5 (cyclohexylamino) 1h pyrazolo[3,4 c]pyridin 3 yl) 2 (phenylamino)acetamide; phosphotransferase; pyrazole derivative; pyridine derivative; unclassified drug; Clk dual-specificity kinases; Dyrk kinase; protein kinase inhibitor; protein serine threonine kinase; protein tyrosine kinase; pyrazole derivative; pyrazolo(3,4-b)pyridine; pyridine derivative, Article; biological activity; calculation; concentration response; crystal structure; drug activity; drug design; drug selectivity; drug synthesis; enzyme inhibition; IC50; molecular docking; structure activity relation; substitution reaction; antagonists and inhibitors; chemical structure; chemistry; dose response; human; metabolism; synthesis, Dose-Response Relationship, Drug; Humans; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors; Protein-Serine-Threonine Kinases; Protein-Tyrosine Kinases; Pyrazoles; Pyridines; Structure-Activity Relationship
DOI:
10.1248/cpb.c16-00704
