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.

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Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, and 1,3-di-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-3-(4‴-hydroxy-2‴-cyclopenten-1‴-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL). In addition, the thymidylate kinase of M. tuberculosis was evaluated as a possible enzymatic target.