A series of phenyloxyethyl and cinnamyl derivatives of substituted uracils were synthesized and found to exhibit potent activity against HIV-RT and HIV replication in cell culture. In general, the cinnamyl derivatives proved superior to the phenyloxyethyl derivatives, however 1-[2-(4-methylphenoxy)ethyl]-3-(3,5-dimethylbenzyl)uracil (19) exhibited the highest activity (EC(50)=0.27 μM) thus confirming that the 3-benzyluracil fragment in the NNRTI structure can be regarded as a functional analogue of the benzophenone pharmacophore typically found in NNRTIs.

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.

Provided for non-commercial research and educational use only.Not for reproduction or distribution or commercial use.This article was originally published in a journal published by Elsevier in cooperation with Mendeleev Communications, and the attached copy is provided for the author's benefit and for the benefit of the author's institution, for non-commercial research and educational use including without limitation use in instruction at your institution, sending it to specific colleagues that you know, and providing a copy to your institution's administrator.

No abstract

No abstract

Despite the widespread use of the COVID-19 vaccines, the search for effective antiviral drugs for the treatment of patients infected with SARS-CoV-2 is still relevant. Genetic variability leads to the continued circulation of new variants of concern (VOC). There is a significant decrease in the effectiveness of antibody-based therapy, which raises concerns about the development of new antiviral drugs with a high spectrum of activity against VOCs. We synthesized new analogs of uracil derivatives where uracil was substituted at the N1 and N3 positions. Antiviral activity was studied in Vero E6 cells against VOC, including currently widely circulating SARS-CoV-2 Omicron. All synthesized compounds of the panel showed a wide antiviral effect. In addition, we determined that these compounds inhibit the activity of recombinant SARS-CoV-2 RdRp. Our study suggests that these non-nucleoside uracil-based analogs may be of future use as a treatment for patients infected with circulating SARS-CoV-2 variants.

А series of uracil derivatives containing a 4-oxoquinazoline fragment bound to the nitrogen atom N3 of the pyrimidine ring by a short methylene bridge was synthesized to search for new antiviral agents. Some compounds in this series are shown to exhibit high inhibitory activity against human cytomegalovirus and the varicella zoster virus in a HEL cell culture.

a b s t r a c tA series of heterocyclic compounds were designed as potential nonnucleoside HIV reverse transcriptase inhibitors. Although the compounds ultimately proved inactive against HIV, during the course of the synthesis, a new and highly facile method to realize N-phenylacetamides was developed. Notably, the new route avoids the intractable workups and byproducts previously reported procedures have been associated with, thereby making this approach highly attractive to adaptation with other heterocyclics.Ó 2012 Elsevier Ltd. All rights reserved.As a part of our ongoing efforts to synthesize aryl and heteroaromatic nonnucleoside HIV reverse transcriptase inhibitors (NNRTIs), we sought to construct a new series of N-3 phenylacetamides for use in alkylating various uracils. The amide unit is one of the most important and widely occurring functional groups; it is present in many natural products and is a key feature of many important drugs. Among the more notable examples of amidecontaining compounds, those found in conjunction with N-heterocycles exhibit diverse and marked pharmacological activities. In particular, the HIV-1 NNRTIs, 1 dihydrofolate reductase (DHFR) inhibitors, 2 and histone deacetylase (HDAC) inhibitors stand out. 3 It is not surprising therefore that there are numerous papers in which amide bond formation has been described. 4 Despite the plethora of available routes, most are plagued with problems, in particular, low yields and difficult workups. As a result, a new and more facile route was sought.A preliminary search of the literature revealed several known methods for the formation of 2-chloroacetanilides. The most commonly used methodology involves condensation of chloroacetyl chloride with various anilines in aprotic solvents (e.g. ether, dioxane, chloroform, dichloromethane, ethyl acetate, or DMF) in the presence of anhydrous K 2 CO 3 , 5 triethylamine 6 or pyridine 7 as the base. Another variant utilizes methylethylketone and CaCO 3 8 while other references describe condensation promoted by triethylamine in acetic acid. 9 Examples of aniline acylation in acetate buffer 10 and aqueous K 2 CO 3 11 are also known, while another approach proposes the synthesis of 2-chloroacetanilides in base-free conditions. In the latter case, the reaction takes place in nonpolar solvent 12 or in a mixed solvent system. 13 Although there are many options available, it is important to note that most of these methods suffer from numerous side reactions arising from either N-quaternization of the organic base or hydrolysis, which lead to low yields and tedious work-up procedures. It has however, been shown that amide bond formation could be achieved by the cleavage of the silicon-nitrogen bonds in TMS-protected alkylamines and anilines by acid halides. 14 The absence of a base renders the silyl method very attractive for the synthesis of 2-chloroacetanilides, as this serves to bypass the problems with side reactions such as quaternization and hydrolysis that are common with the aforementioned routes. Surpri...