Abstract
Synthesis, biological evaluation, and SAR dependencies for a series of novel aryl and heteroaryl substituted N-[3-(4-phenylpiperazin-1-yl)propyl]-1,2,4-oxadiazole-5-carboxamide inhibitors of GSK-3beta kinase are described. The inhibitory activity of the synthesized compounds is highly dependent on the character of substituents in the phenyl ring and the nature of terminal heterocyclic fragment of the core molecular scaffold. The most potent compounds from this series contain 3,4-di-methyl or 2-methoxy substituents within the phenyl ring and 3-pyridine fragment connected to the 1,2,4-oxadiazole heterocycle. These compounds selectively inhibit GSK-3beta kinase with IC(50) value of 0.35 and 0.41 microM, respectively.
MeSH terms
-
Dose-Response Relationship, Drug
-
Drug Evaluation, Preclinical
-
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
-
Glycogen Synthase Kinase 3 beta
-
Inhibitory Concentration 50
-
Molecular Structure
-
Oxadiazoles / chemical synthesis
-
Oxadiazoles / chemistry
-
Oxadiazoles / pharmacology*
-
Piperazines / chemical synthesis
-
Piperazines / chemistry
-
Piperazines / pharmacology*
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Small Molecule Libraries
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
Oxadiazoles
-
Piperazines
-
Protein Kinase Inhibitors
-
Small Molecule Libraries
-
Glycogen Synthase Kinase 3 beta
-
Glycogen Synthase Kinase 3