Synthesis, Docking Study and Kinase Inhibitory Activity of a Number of New Substituted Pyrazolo[3,4-c]pyridines

Meropi Sklepari; Nikolaos Lougiakis; Athanasios Papastathopoulos; Nicole Pouli; Panagiotis Marakos; Vassilios Myrianthopoulos; Thomas Robert; Stéphane Bach; Emmanuel Mikros; Sandrine Ruchaud

doi:10.1248/cpb.c16-00704

Regular Articles

Synthesis, Docking Study and Kinase Inhibitory Activity of a Number of New Substituted Pyrazolo[3,4-c]pyridines

Meropi Sklepari, Nikolaos Lougiakis, Athanasios Papastathopoulos, Nicole Pouli, Panagiotis Marakos , Vassilios Myrianthopoulos, Thomas Robert, Stéphane Bach, Emmanuel Mikros, Sandrine Ruchaud

Author information

Meropi Sklepari
School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens
Nikolaos Lougiakis
School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens
Athanasios Papastathopoulos
School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens
Nicole Pouli
School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens
Panagiotis Marakos Corresponding author
School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens
Vassilios Myrianthopoulos
School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens
Thomas Robert
Sorbonne Universities, UPMC Univ. Paris 06, CNRS USR 3151, Protein Phosphorylation & Human Diseases, Station Biologique de Roscoff
Stéphane Bach
Sorbonne Universities, UPMC Univ. Paris 06, CNRS USR 3151, Protein Phosphorylation & Human Diseases, Station Biologique de Roscoff
Emmanuel Mikros
School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens
Sandrine Ruchaud
Sorbonne Universities, UPMC Univ. Paris 06, CNRS USR 3151, Protein Phosphorylation & Human Diseases, Station Biologique de Roscoff

Keywords: pyrazolopyridine, kinase inhibition, glycogen synthase kinase 3 (GSK3)α/β, purine analogue, molecular simulation

JOURNAL FREE ACCESS FULL-TEXT HTML

2017 Volume 65 Issue 1 Pages 66-81

DOI https://doi.org/10.1248/cpb.c16-00704

Details

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.

Graphical Abstract Fullsize Image

Corresponding author

Register with J-STAGE for free!