188781-06-8Relevant articles and documents
A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones
Fesenko, Anastasia A.,Solovyev, Pavel A.,Shutalev, Anatoly D.
experimental part, p. 940 - 946 (2010/03/24)
A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones or β-oxoesters followed by heterocycliz
PROCESS FOR THE PRODUCTION OF PYRIMIDINE-5-CARBOXYLATES
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Page/Page column 9, (2008/06/13)
Pyrimidine-5-carboxylates of formula wherein R is C1-4 alkyl, R1 is C1_4 alkyl or trifluoromethyl, R2 is hydrogen or C1 alkyl and X is hydroxy, chlorine or bromine, are prepared from 3-oxoalkanoates of formula with urea and orthoesters of formula R2C(OR)3 (III). The intermediate 2-acyl-3-ureidoacrylate, without being isolated, is reacted to give a 2-hydroxypyrimidine-5-carboxylate [(I), X = OH] or a hydrate thereof, which is optionally converted into the corresponding chloro or bromo compound (I, X = Cl, Br).
Inhibitors of NF-kappaB and AP-1 gene expression: SAR studies on the pyrimidine portion of 2-chloro-4-trifluoromethylpyrimidine-5-[N-(3', 5'-bis(trifluoromethyl)phenyl)carboxamide].
Palanki,Erdman,Gayo-Fung,Shevlin,Sullivan,Goldman,Ransone,Bennett,Manning,Suto
, p. 3995 - 4004 (2007/10/03)
We investigated the structure-activity relationship studies of N-[3, 5-bis(trifluoromethyl)phenyl][2-chloro-4-(trifluoromethyl)pyrimidin-5 -yl]carboxamide (1), an inhibitor of transcription mediated by both NF-kappaB and AP-1 transcription factors, with the goal of improving its potential oral bioavailability. Compounds were examined for cell-based activity, were fit to Lipinski's rule of 5, and were examined for potential gastrointestinal permeability using the intestinal epithelial cell line, Caco-2. Selected groups were substituted at the 2-, 4-, and 5-positions of the pyrimidine ring using solution-phase combinatorial methodology. The introduction of a fluorine in the place of 2-chlorine of 1 resulted in a compound with comparable activity. However, other substitutions at the 2-position resulted in a loss of activity. The trifluoromethyl group at the 4-position could be replaced with a methyl, ethyl, chlorine, or phenyl without a substantial loss of activity. The carboxamide group at the 5-position is critical for activity. If it was moved to the 6-position, the activity was lost. The 2-methyl analogue of 1 (81) showed comparable in vitro activity and improved Caco-2 permeability compared to 1.
