The systematic study of pyrimidines began in 1884 with Pinner, who synthesized derivatives by condensing ethyl acetoacetate with amidines. Pinner first proposed the name “pyrimidin” in 1885. 109-12-6, formula is C4H5N3, Name is Pyrimidin-2-amine. The parent compound was first prepared by Gabriel and Colman in 1900, by conversion of barbituric acid to 2,4,6-trichloropyrimidine followed by reduction using zinc dust in hot water. Synthetic Route of 109-12-6.
Guo, Ming;Zuo, Daiying;Zhao, Tianming;Li, Xiangyu;Cao, Jianshuang;Qiu, Yuxuan;Wei, Shangfei;Zhai, Xin research published 《 Structure-based optimization identified novel furyl-containing 2,4-diarylaminopyrimidine analogues as ALK/ROS1 dual inhibitors with anti-mutation effects》, the research content is summarized as follows. Aiming to develop ALK/ROS1 dual inhibitors overcoming ceritinib-resistant G1202R mutant, a dedicated structure-guided modification campaign was conducted based on ALK co-crystal structures. Twenty eight diarylaminopyrimidine (DAAP) analogs I [R = methanesulfonyl, acetyl; R1 = furan-2-yl, oxolan-2-yl, (furan-2-ylmethyl)dimethylamine, etc.; X = O, NH, SO2] possessing furan or THF group were designed and synthesized, among which compound I [R = methanesulfonyl, R1 = (furan-2-ylmethyl)dimethylamine, X = S] bearing ((((dimethylamino)methyl)furan-2-yl)methyl)thio fragment was identified. Compound I [R = methanesulfonyl, R1 = (furan-2-ylmethyl)dimethylamine, X = S] exhibited significant cytotoxicity on ALK-pos. Karpas299 and H2228 cells with IC50 values of 20 nM and 110 nM. Meanwhile, compound I [R = methanesulfonyl, R1 = (furan-2-ylmethyl)dimethylamine, X = S] turned out as the most potent entity superior to ceritinib with IC50 values of 2.8, 2.6, 3.8 and 2.3 nM against ALKWT, ALKL1196M, ALKG1202R and ROS1WT, resp. Subsequently, western blot assay showed that compound I [R = methanesulfonyl, R1 = (furan-2-ylmethyl)dimethylamine, X = S] significantly suppressed ALK and its downstream protein expression in a dose-dependent manner. Alternatively, the Hoechst 33258 and AO/EB staining assays illustrated that compound I [R = methanesulfonyl, R1 = (furan-2-ylmethyl)dimethylamine, X = S] could induce H2228 cell apoptosis. Ultimately, the binding models of compound I [R = methanesulfonyl, R1 = (furan-2-ylmethyl)dimethylamine, X = S] with ALKWT, ALKG1202R as well as ROS1 clearly presented the essential interactions within the active site. Together, compound I [R = methanesulfonyl, R1 = (furan-2-ylmethyl)dimethylamine, X = S] was validated as a promising ALK/ROS1 dual inhibitor for ALKG1202R mutation correlated tumors.
109-12-6, 2-Aminopyrimidine is a useful research compound. Its molecular formula is C4H5N3 and its molecular weight is 95.1 g/mol. The purity is usually 95%.
2-Aminopyrimidine is an organic compound that belongs to the group of pyridines. It has been shown to have antimicrobial, antitumor, and antiviral properties. 2-Aminopyrimidine has been used as a fungicide and herbicide in horticulture and agriculture, respectively. The molecular geometry of this molecule is octahedral with coordination geometry C2v. This chemical binds to the BCR-ABL kinase receptor and inhibits its activity by competitive inhibition of ATP binding. 2-Aminopyrimidine has been shown to have a hematologic response in vivo models and in vitro assays. It also has anti-inflammatory effects when it is taken orally or applied topically., Synthetic Route of 109-12-6
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia