13428-25-6Relevant academic research and scientific papers
Pyrimidine derivative, preparation method thereof, application , and pharmaceutical composition
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Paragraph 0075; 0081-0082, (2021/01/29)
The invention relates to the technical field of chemical medicines and relates to a pyrimidine derivative, a preparation method thereof, application and a pharmaceutical composition. The structural formula of the pyrimidine derivative is shown in the specification, wherein R1 and R1'are respectively and independently selected from any one of substituted or unsubstituted alkyl, H and substituted orunsubstituted naphthenic base, R2 and R2'are respectively and independently selected from any one of H, substituted or unsubstituted alkyl, substituted or unsubstituted naphthenic base, halogen, -NH2, -NO2 and -CN, R3, R3 ', R4 and R4' are respectively and independently selected from any one of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and Y-X. The novel pyrimidine derivative has an excellent inhibitory effect on kinase, and particularly has a remarkable inhibitory effect on PLK4, and the novel pyrimidine derivative can inhibit tumor growth.
Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands
Altenbach, Robert J.,Adair, Ronald M.,Bettencourt, Brian M.,Black, Lawrence A.,Fix-Stenzel, Shannon R.,Gopalakrishnan, Sujatha M.,Hsieh, Gin C.,Liu, Huaqing,Marsh, Kennan C.,McPherson, Michael J.,Milicic, Ivan,Miller, Thomas R.,Vortherms, Timothy A.,Warrior, Usha,Wetter, Jill M.,Wishart, Neil,Witte, David G.,Honore, Prisca,Esbenshade, Timothy A.,Hancock, Arthur A.,Brioni, Jorge D.,Cowart, Marlon D.
supporting information; experimental part, p. 6571 - 6580 (2009/11/30)
A series of 2-aminopyrimidines was synthesized as ligands of the histamine H4 receptor (H4R). Working in part from a pyrimidine hit that was identified in an HTS campaign, SAR studies were carried out to optimize the potency, which led to compound 3,4-tert-butyl-6-(4-methylpiperazin-1-yl) pyrimidin-2-ylamine. We further studied this compound by systematically modifying the core pyrimidine moiety, the methylpiperazine at position 4, the NH2 at position 2, and positions 5 and 6 of the pyrimidine ring. The pyrimidine 6 position benefited the most from this optimization, especially in analogs in which the 6-tert-butyl was replaced with aromatic and secondary amine moieties. The highlight of the optimization campaign was compound 4,4-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]benzonitrile, which was potent in vitro and was active as an anti-inflammatory agent in an animal model and had antinociceptive activity in a pain model, which supports the potential of H4R antagonists in pain.
