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.
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.
Palanki
M S
MS
Signal Pharmaceuticals, Inc., San Diego, CA 92121, USA. mpalanki@signalpharm.com
Erdman
P E
PE
Manning
A M
AM
Ow
A
A
Ransone
L J
LJ
Spooner
C
C
Suto
C
C
Suto
M
M
D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D008301:Maleimides / Q000737:chemistry / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
D008301:Maleimides; D016328:NF-kappa B; D011743:Pyrimidines; D018808:Transcription Factor AP-1; C416352:ethyl 4-(3-methyl-2,5-dioxo(3-pyrrolinyl)amino)-2-(trifluoromethyl)pyrimidine-5-carboxylate