2-(2,4-Dioxy-1,2,3,4-Tetrahydropyrimidin-1-yl)-N-(4-Phenoxyphenyl)-Acetamides as a Novel Class of Cytomegalovirus Replication Inhibitors

Abstract

A series of novel uracil derivatives, bearing N-(4-phenoxyphenyl)acetamide moiety at N3 of a pyrimidine ring, has been synthesized. Their antiviral activity has been evaluated. It has been found that the novel compounds possess high inhibitory activity against replication of human cytomegalovirus (AD-169 and Davis strains) in HEL cell cultures. In addition, some of the derivatives proved to be inhibitory against varicella zoster virus.

Computational Modeling, Docking, Synthesis, Characterization, and in vitro Cyclooxygenase Inhibitory Activity of Some Novel Non-Steroidal Anti-inflammatory Prodrugs

“…The interest in synthesizing poly-functional molecules is increasing nowadays. Acetamides can be considered as a poly-functional molecules since their derivatives were found to possess various bioactive properties such as; anthelmintic (Sawant and Kawade, 2011), anticonvulsant (Kamiński et al, 2011) (Jawed et al, 2010), antioxidant (Ayhan-Kılcıgil et al, 2012) (Autore et al, 2010), anti-inflammatory (Jain et al, 2013) (Autore et al, 2010), anti-arthritic (Jain et al, 2013), anti-bacterial (Kanagarajan and Gopalakrishnan, 2012) (Nayak et al, 2014), antifungal (Bardiot et al, 2015) (Kidwai et al, 2012) (Kanagarajan, Thanusu and Gopalakrishnan, 2010), and anti-viral properties (Babkov et al, 2015) (Kai et al, 2001).…”

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

“…Earlier, we synthesized uracil derivatives containing acetanilide fragment at N 3 atom of the uracil residue. 18,19 Compounds of this series demonstrated a broad spectrum of antiviral activity against cytomegaloviruses, varicella-zoster virus 19 and hepatitis C virus. 20 We also recently obtained uracil derivatives containing coumarin residue at the 3-position, which were active against HCMV and varicella-zoster virus.…”

“…The synthesis of this series of compounds (Scheme 1) consisted of the preparation of starting chloro acetanilides 1a-e, which included treatment of 4-phenoxyaniline and its substituted derivatives with chloroacetyl chloride in 1,2-dichloro ethane in the presence of K 2 CO 3 at 0 °C under the conditions described. 18 The preparation of 1-[8-(4-bromo phenoxy)octyl]uracil 2a was known. 19 The synthesis of its decane-1,10-diyl and dodecane-1,12-diyl homologues 2b,c was carried out under the conditions of silyl version of the Hilbert-Johnson reaction by condensation of equimolar amounts of 2,4-bis(trimethylsilyloxy)pyrimidine and the corresponding 1-bromo-ω-(p-bromophenoxy)alkanes at 160-170 °C for 1 h (see Scheme 1) as described.…”