Synthesis of uracil–coumarin conjugates as potential inhibitors of virus replication

Antiviral Activity of N1,N3-Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern

“…The target acids were synthesized by treating the starting 1-(naphthalen-1-ylmethyl)uracil ( 1 ) [ 22 ], 1-(naphthalen-2-ylmethyl)uracil ( 2 ) [ 22 ], 1-(4-bromonaphthalen-1-ylmethyl)uracil ( 3 ) [ 22 ], 1-(anthrecen-9-ylmethyl)uracil ( 4 ) [ 23 ], 1-[3-(4-bromophenoxy)propyl]uracil ( 5 ) [ 24 ], 1-[5-(4-fluorophenoxy)pentyl]uracil ( 6 ), 1-[5-(2-bromophenoxy)pentyl]uracil ( 7 ) [ 25 ], 1-[5-(4-bromo-phenoxy)pentyl]uracil ( 8 ) [ 24 ], 1-[5-(3,5-dimethylphenoxy)pentyl]uracil ( 9 ) [ 26 ] or 1-[12-(4-bromophenoxy)dodecyl]uracil ( 10 ) [ 17 ] with an equimolar amount of 4-(ω-bromoalkoxy)benzoic acid methyl ester ( 11–13 ) in DMF solution in the presence of K 2 CO 3 . The resulting 1,3-disubstituted uracil without further purification was subjected to alkaline hydrolysis in an aqueous-alcoholic solution, which led to the formation of the corresponding benzoic acids ( Scheme 1 ).…”

Uracil: A Pharmacophore with Diverse Biological Potential

“…Paramonova et al [63] developed a new method for the synthesis of uracil-coumarin conjugates of the type 105 a-f. The reaction was carried out between 1-[(bromophenoxy)alkyl]uracil derivative 103 and 7-(w-bromoalkoxy)-4-methyl-2H-chromen-2ones 104 in the presence of potassium carbonate using DMF as a solvent (Scheme 28).…”

Synthesis and antiviral properties of 1-substituted 3-[ω-(4-oxoquinazolin-4(3h)-yl)alkyl]uracil derivatives

“…These compounds inhibited the replication of HCMV, VZV [ 21 ], and HCV [ 22 ]. Replacing the acetamide fragment with a coumarin residue has given rise to a number of compounds that also effectively inhibit the replication of HCMV and VZV [ 23 ]. In continuation of our research focused on effective viral replication blockers, we synthesized a number of 1-[ω-(aryloxy)alkyl]uracil derivatives carrying a quinazolin-4(3H)-one moiety bound to the N3 atom in the pyrimidine ring by a linker consisting of two or three methylene groups.…”