Structure-activity relationship studies of ethyl 2-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-4-(trifluoromethyl)pyrimidine-5-carboxylate: an inhibitor of AP-1 and NF-kappaB mediated gene expression.
Several analogues of ethyl 2-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-4-(trifluoromethyl)pyrimidine-5-carboxylate (1) were synthesized and tested as inhibitors of AP-1 and NF-kappaB mediated transcriptional activation in Jurkat T cells. From our SAR work, ethyl 2-[(3-methyl-2,5-dioxo(3-pyrrolinyl))-N-methylamino]-4-(trifluoromethyl)-pyrimidine-5-carboxylate was identified as a novel and potent inhibitor.
Palanki
Moorthy S S
MS
Celgene Signal Research Division, 5555 Oberlin Drive, San Diego, CA 92121, USA. mpalanki@signalpharm.com
Gayo-Fung
Leah M
LM
Shevlin
Graziella I
GI
Erdman
Paul
P
Sato
Mark
M
Goldman
Mark
M
Ransone
Lynn J
LJ
Spooner
Cheryl
C
D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000502:physiology
D016328:NF-kappa B; D011743:Pyrimidines; D011758:Pyrroles; D018808:Transcription Factor AP-1; C470970:ethyl-2-((3-methyl-2,5-dioxo(3-pyrrolinyl))amino)-4-(trifluoromethyl)pyrimidine-5-carboxylate