Effect of acyclic pyrimidines related to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine on herpes viruses

Abstract

A series of pyrimidines related to the potent antiherpetic agent 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (1, BW B759U), all containing the same acyclic chain, have been synthesized. Some of the compounds were derivatives of the naturally occurring bases, cytosine, uracil, and thymine; others included compounds in which the 5-position of the cytosine and uracil moieties were substituted by bromo, iodo, fluoro, methyl, and amino groups. Other variations of the cytosine derivatives were the 5-aza, 2-mercapto, 4-methylamino, 4-dimethylamino, and isocytosine congeners. A 4-aminopyrimidine adduct was also made. Antiviral testing showed that 1-[(1,3-dihydroxy-2-propoxy)methyl]cytosine (18, BW A1117U) was equivalent to the guanine analogue in potency against human cytomegalovirus and Epstein Barr virus. Other compounds in the series were largely inactive in antiviral screening against the herpesviruses.

Tautomerism and the Protonation/Deprotonation of Isocytosine in Liquid‐ and Solid‐States Studied by NMR Spectroscopy and Theoretical Calculations

“…[2][3][4][5][6][7] The synthesis of antiviral compounds through the incorporation of an isocytosine unit has also been reported. [8,9] Recently, isocytosine has gained interest as a lead compound applicable for the treatment of Alzheimer's disease. [10,11] The C5 nucleoside of isocytosine is known as an antileukemia drug [12] and is a valuable tool in molecular biology, for example, for DNA triplex formation [13] and mechanistic studies of RNA catalysis.…”

Isocytosine as a Hydrogen‐Bonding Partner and as a Ligand in Metal Complexes

“…Merging of redundant reflections in part eliminates absorption effects and also considers crystal decay if present. The SHELXTL 5.1 [46] package was used to solve and refine the structures by direct (2, 3) and Patterson methods (4,5). Hydrogen atoms were located in a difference Fourier map and refined isotropically while all non-hydrogen atoms were treated anisotropically.…”

“…ICH exists as two major tautomers, 1 a and 1 b, [1] which crystallize in a 1:1 ratio and form a hydrogen-bonded adduct [2] in the solid state (Scheme 1). The N 1 [3,4] and C…”

Relativistic study of tautomerism and core electron binding energies of thio- and selenocytosine

“…The thiocytosine tautomers base have been found in Escherichia coli tRNA [43][44][45]. Its nucleosides exhibit moderate inhibitory activity against vaccine and Epstein-Barr viruses in cell cultures and fluorinated 2-thiocytidine has shown potent antileukemic activity [46][47][48]. Substitution of oxygen in a carbonyl group of cytosine by selenium causes changes in molecular properties associated with the C=X group.…”