Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof

Abstract

HCMV infection represents a life-threatening condition for immunocompromised patients and newborn infants and novel anti-HCMV agents are clearly needed. In this regard, a series of 1-[ω-(phenoxy)alkyl]uracil derivatives were synthesized and examined for antiviral properties. Compounds 17, 20, 24 and 28 were found to exhibit highly specific and promising inhibitory activity against HCMV replication in HEL cell cultures with EC50 values within 5.5-12μM range. Further studies should be undertaken to elucidate the mechanism of action of these compounds and the structure-activity relationship for the linker region.

Novel 1-[5-(4-bromophenoxy)pentyl]-3-(2-arylamino- 2-oxoethyl)uracils and their antiviral properties

“…13 16 Disappointingly, none of the com pounds in this series showed any meaningful antiviral activity. A mixture of 1-[5-(4-bromophenoxy)pentyl]uracil 6 (0.5 g, 1.42 mmol) and K 2 CO 3 (0.3 g, 2.17 mmol) in DMF (10 ml) was stirred at 80 °C for 1 h. After cooling to room temperature, the corresponding 2-chloro acetamide 8-11 (1.46 mmol) was added and stirring was continued for 24 h. The reaction mixture was filtered, concentrated under reduced pressure, puri fied by flash chromatography eluting with 1,2-dichloroethane-EtOAc (1 : 2) and then recrystallized from a mixture of hexane-EtOAc (1 : 1).…”

“…15 Conversion of the correspon ding anilines into their N-trimethylsilyl derivatives was 16 with the corresponding chloroacetamides 8-11 in DMF in the presence of a 1.5-fold excess of potassium carbonate led to the target compounds 2-5 in 78-90% yields. † This approach employed substituted N-aryl-2-chloroacetamides as alkyla ting agents.…”

Toward the discovery of dual HCMV–VZV inhibitors: Synthesis, structure activity relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N-(4-phenoxyphenyl)acetamides

“…Based on the successful synthesis of several previously reported compounds, 9 a series of analogs were synthesized following the classical synthetic approach reported in Scheme 1. Based on the successful synthesis of several previously reported compounds, 9 a series of analogs were synthesized following the classical synthetic approach reported in Scheme 1.…”

“…4,5 The emergence of drug resistance is also a significant problem. 9 These results provided strong impetus to further explore structure-activity relationships and the antiviral activity spectrum of similar scaffolds. 7 While the past two decades have seen progress toward novel treatments for herpesviruses, the need for better drugs that exhibit an improved toxicity profile persists.…”

Synthesis and Structural Studies of Three Uracil Derivatives, Methyl 3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanate, Methyl 3-(5-Nitro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanoate and Ethyl 3-(5-Nitro-2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)propanoate

“…The vibrational studies on uracil and 5-substituted uracils have also been made by several researchers, which regarded be helpful in understanding their scientific vibrational results with the view of biological process and in the analysis of relatively complex systems [5][6][7][8][9][10][11][12]. Moreover, the biological activity of uracil and its derivatives has stimulated exceptional interest in biochemistry and pharmacology [13][14][15][16][17][18]. In particular, substitution at the C5 site of uracil yields derivatives with outstanding properties.…”