Novel heterocycle-substituted pyrimidines as inhibitors of NF-kappaB transcription regulation related to TNF-alpha cytokine release

Hyung-Ho Ha; Jee Seon Kim; B Moon Kim

doi:10.1016/j.bmcl.2007.11.064

Novel heterocycle-substituted pyrimidines as inhibitors of NF-kappaB transcription regulation related to TNF-alpha cytokine release

Bioorg Med Chem Lett. 2008 Jan 15;18(2):653-6. doi: 10.1016/j.bmcl.2007.11.064. Epub 2007 Nov 22.

Authors

Hyung-Ho Ha¹, Jee Seon Kim, B Moon Kim

Affiliation

¹ Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea.

PMID: 18054489
DOI: 10.1016/j.bmcl.2007.11.064

Abstract

Novel heterocyclic ring-substituted pyrimidines have been designed as inhibitors of glycogen synthase kinase-3beta (GSK-3beta) from the modification of known inhibitors. Several potent inhibitors exhibiting nanomolar activities were discovered against GSK-3beta kinase as well as in an NF-kappaB reporter gene assay. Based on the results from in vitro TNF-alpha release inhibition and in vivo endotoxima, these inhibitors are expected to be useful candidates for treatment of inflammation-related diseases.

MeSH terms

Enzyme Inhibitors / pharmacology
Gene Expression Regulation / drug effects*
Glycogen Synthase Kinase 3 / antagonists & inhibitors
Glycogen Synthase Kinase 3 beta
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology*
Humans
NF-kappa B / antagonists & inhibitors*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Transcription, Genetic / drug effects*
Tumor Necrosis Factor-alpha / metabolism*

Substances

Enzyme Inhibitors
Heterocyclic Compounds
NF-kappa B
Pyrimidines
Tumor Necrosis Factor-alpha
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3