13345-11-4Relevant articles and documents
Desulfurization of 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ones with oxiranes and 2-haloacetonitriles
Novakov,Orlinson,Navrotskii
, p. 607 - 609 (2005)
A procedure was developed for the synthesis of tetrahydropyrimidine-2,4- diones by desulfurization of 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ones with oxiranes or 2-haloacetonitriles in polar solvents in the presence of a base.
Design, synthesis, and biological evaluation of 1-[(2-benzyloxyl/alkoxyl) methyl]-5-halo-6-aryluracils as potent HIV-1 non-nucleoside reverse transcriptase inhibitors with an improved drug resistance profile
Wang, Xiaowei,Zhang, Jianfang,Huang, Yang,Wang, Ruiping,Zhang, Liang,Qiao, Kang,Li, Li,Liu, Chang,Ouyang, Yabo,Xu, Weisi,Zhang, Zhili,Zhang, Liangren,Shao, Yiming,Jiang, Shibo,Ma, Liying,Liu, Junyi
experimental part, p. 2242 - 2250 (2012/05/20)
Because the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]- 5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b, and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains. Compound 7b, which had the highest selectivity index (SI = 38 215), is more potent than nevirapine and 18. These results suggest that the introduction of a halogen at the C-5 position may contribute to the effectiveness of these compounds against RTI-resistant variants. In addition, meta substituents on the C-6 aromatic moiety could significantly enhance activity against NNRTI-resistant HIV-1 strains. These compounds can be further developed as next-generation NNRTIs with an improved antiviral efficacy and drug-resistance profile.
DNA-protein cross-linking: Model systems for pyrimidine-aromatic amino acid cross-linking
Sun, Guangxing,Fecko, Christopher J.,Nicewonger, Robert B.,Webb, Watt W.,Begley, Tadhg P.
, p. 681 - 683 (2007/10/03)
We have synthesized simple model systems to explore the possibility of photo-cross-linking between the pyrimidine bases and the side chains of the aromatic amino acids. Thymine/phenylalanine and thymine/tyrosine models gave cross-links, and thymine/tryptophan models gave complex mixtures; the cytosine/phenylalanine model was unreactive. The quantum yields for the model cross-linking reactions were 18-46 times smaller than those for thymine dimer formation. Biphotonic excitation contributes little to the yield of these reactions.
