5579-48-6Relevant academic research and scientific papers
An optimized synthesis, molecular structure and characterization of benzylic derivatives of 1,2,4-Triazin-3,5(2H,4H)-dione
Hwang, Long-Chih,Yang, Shiun-Yau,Chuang, Chung-Lin,Lee, Gene-Hsiang
, (2017)
4-Benzyl-1,2,4-triazin-3,5(2H,4H)-dione (3-benzyl-6-azauracil, 2), and 2,4-dibenzyl-1,2,4-triazin-3,5(2H,4H)-dione (1,3-dibenzyl-6-azauracil, 3) were synthesized by the reaction of 1,2,4-triazin-3,5(2H,4H)-dione (6-azauracil, 1) with benzyl bromide and potassium carbonate in dry acetone via the 18-crown-6-ether catalysis. In these reaction methods, we developed more convenient and efficient methodologies to afford compounds 2 and 3 in good yields. These compounds were characterized by1H- and13C-NMR, MS spectrum, IR spectroscopy and elemental analysis. The structure of 2 was verified by 2D-NMR measurements, including gHSQC and gHMBC measurements. A single-crystal X-ray diffraction experiment indicated that compound 3, with the molecular formula C17H15N3O2, crystallized from a CH3OH/CH2Cl2 diffusion solvent system in a monoclinic space group P21/c with a = 13.7844(13), b = 8.5691(8), c = 13.0527(12), β = 105.961(2)?, V = 1482.3(2)3, Z = 4, resulting in a density Dcalc of 1.314 g/cm3. The crystal structure of compound 3 is tightly stabilized by contact with five other molecules from the six short contacts formed by intermolecular C?O···H?Car, C?H···Car, and weakly π···π stacking interactions. The dihedral angle 31.90? is formed by the mean planes of the benzene rings of the N-2 and N-4 benzyl groups.
Anticoccidial derivatives of 6 azauracil. I. Enhancement of activity by benzylation of nitrogen 1. Observations on the design of nucleotide analogues in chemotherapy
Mylari,Miller,Howes Jr.,Figdor,Lynch,Koch
, p. 475 - 483 (2007/10/09)
Benzylation of 6-azauracil at N-1 (which corresponds to the point of attachment of the ribose phosphate unit in pyrimidine nucleotides) has been found to augment its anticoccidial activity fourfold. The high potency of 1-benzyl-6-azauracil is ascribed to a combination of intrinsic activity, efficient oral absorption, and a moderate rate of excretion. Metabolism experiments using 1-benzyl-6-azauracil labeled with 14C in the heterocycle and (separately) in the side chain showed that, in the drug accounted for, no cleavage had occurred. Additional activity increases were achieved by introducing small, electron-withdrawing substituents in the meta and/or para position(s) of the benzyl group. One of the most active derivatives, 1-(3-cyanobenzyl)-6-azauracil, is about 16 times as potent as 6-azauracil.
