Novel inhibitors of AP-1 and NF-kappaB mediated gene expression: structure-activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)++ +pyrimidi ne-5-carboxylate

M S Palanki; P E Erdman; A M Manning; A Ow; L J Ransone; C Spooner; C Suto; M Suto

doi:10.1016/s0960-894x(00)00312-7

Novel inhibitors of AP-1 and NF-kappaB mediated gene expression: structure-activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)++ +pyrimidi ne-5-carboxylate

Bioorg Med Chem Lett. 2000 Aug 7;10(15):1645-8. doi: 10.1016/s0960-894x(00)00312-7.

Authors

M S Palanki¹, P E Erdman, A M Manning, A Ow, L J Ransone, C Spooner, C Suto, M Suto

Affiliation

¹ Signal Pharmaceuticals, Inc., San Diego, CA 92121, USA. mpalanki@signalpharm.com

PMID: 10937715
DOI: 10.1016/s0960-894x(00)00312-7

Abstract

In an effort to identify novel inhibitors of AP-1 and NF-kappaB mediated transcriptional activation, several analogues of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyr imidine-5-carboxylate (1) were synthesized and tested in two in vitro assays. The 2-(2'-thienyl) substituted compound (11) was identified as the most potent in this series.

MeSH terms

Gene Expression Regulation / drug effects*
Humans
Jurkat Cells
Maleimides / chemistry
Maleimides / pharmacology*
NF-kappa B / antagonists & inhibitors*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship
Transcription Factor AP-1 / antagonists & inhibitors*

Substances

Maleimides
NF-kappa B
Pyrimidines
Transcription Factor AP-1
ethyl 4-(3-methyl-2,5-dioxo(3-pyrrolinyl)amino)-2-(trifluoromethyl)pyrimidine-5-carboxylate