New acetamide derivatives containing (ω-p-bromophenoxyalkyl)uracil moiety and their anticytomegalovirus activity

Abstract

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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 ).…”

“…Previously, the antiviral activity of various non-nucleoside uracil derivatives was demonstrated. These compounds inhibited the replication of HCMV [ 17 ], VZV [ 18 ], HIV [ 19 ] and HCV [ 20 ]. Moreover, ramified derivatives of uracil presented antiviral activity against tick-borne encephalitis virus (TBEV) [ 21 ].…”

Synthesis of 1-[ω-(Bromophenoxy)alkyl]-3-Naphthalenylmethyl Uracil Derivatives and Their Analogues as Probable Inhibitors of Human Cytomegalovirus Replication

“…Obtaining the starting 1-[ω-(4-bromophenoxy)alkyl]uracil derivatives 1–6 was described earlier [ 15 ]. The synthesis of 1-[5-(3-bromophenoxy)uracil ( 7 ) was described by Paramonova et al [ 21 ]. The target compounds of the naphthalenylmethyl series were obtained by alkylation of 1-[ω-(phenoxy)alkyl]uracil derivatives 1–7 with 1-(bromomethyl)naphthalene ( 8 , R 3 = H), 2-(bromomethyl)naphthalene ( 9 , R 3 = H), or 1-bromo-2-(bromomethyl)naphthalene ( 10 , R 3 = Br) under previously described conditions [ 18 , 22 ].…”

“…of Cytostatic Activity Compounds were tested against the following viruses: human cytomegalovirus (HCMV, strains AD-169 and Davis) and varicella zoster virus (VZV, strains OKA and YS). Antiviral studies were based on the inhibition of virus-induced cytopathic effect or plaque formation in human embryonic lung (HEL) cells as described earlier [21].…”

“…We have recently discovered a series of uracil 1-cinnamyl derivatives containing benzyl and naphthalen-1-ylmethyl substituents at the nitrogen atom N 3 , which also exhibited activity against HIV-1 and HCMV [ 19 ]. In addition, a high anti-HCMV activity was shown for 1-[5-(4-bromophenoxy)pentyl]uracil derivatives, which had 3-(4-oxoquinazolin-3(4 H )-yl)propyl [ 20 ] or 3-[(4-methyl-2-oxo-2 H -chromen-7-yl)oxy]propyl substituent at the nitrogen atom N 3 [ 21 ].…”