N1,N3-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase

Abstract

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.

Synthesis, anti-varicella-zoster virus and anti-cytomegalovirus activity of quinazoline-2,4-diones containing isoxazolidine and phosphonate substructures

“…2) has been discovered in recent years [19]. A 3-benzylquinazolin-2,4-dione derivative 1 was reported to posses the anti-HIV-1 activity in MT-4 cells and inhibited the recombinant RT in vitro [20]. A quinazolinone-2,4dione 2 was a potent inhibitor of RSV-induced cytopathic effect (EC 50 ¼ 2.14 mM) [21].…”

Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof

“…Specifically, the anti-HIV and anti-HCMV activity for a series of 9-[2-(phenoxy)ethyl]-and 9-[2-(benzyloxy)ethyl]-derivatives of adenine have been described. 39 As a result, these observations provided strong impetus to further explore the antiviral activity spectrum of 1-[x-(phenoxy)alkyl]uracils, as well as to investigate the structural requirements for the linker between the aromatic moieties, since this scaffold is common to many known inhibitors of HCMV polymerase. 38 In addition, several derivatives of 3-benzyl-1-(cinnamyl)uracil demonstrated significant activity against HIV and HCMV replication in cell culture.…”

Synthesis of Some New Benzisothiazolone and Benzenesulfonamide Derivatives of Biological Interest Starting from Saccharin Sodium

“…The treatment of viral infections still remains an important and challenging problem because of the emergence of new viral strains resistant to clinically used antiviral agents . In the search for antiviral agents, numerous nonnucleoside derivatives have received considerable attention ; among them, thiazole scaffold has been gaining prominence due to the fact that its derivatives such as compound BILS 179 BS (A) and the clinically used drug ritonavir (B) have been known to possess antiviral activity against HSV and HIV, respectively (Fig. ).…”