Derivatives of imidazotriazine and pyrrolotriazine C-nucleosides as potential new anti-HCV agents.

Previous investigations identified 2'-C-Me-branched ribo-C-nucleoside adenosine analogues, 1, which contains a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base, and 2, which contains an imidazo[2,1-f][1,2,4]triazin-4-amine heterocyclic base as two compounds with promising anti-HCV in vitro activity. This Letter describes the synthesis and evaluation of a series of novel analogues of these compounds substituted at the 2-, 7-, and 8-positions of the heterocyclic bases. A number of active new HCV inhibitors were identified but most compounds also demonstrated unacceptable cytotoxicity.

Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents.

Nucleoside analogues have long been recognized as prospects for the discovery of direct acting antivirals (DAAs) to treat hepatitis C virus because they have generally exhibited cross-genotype activity and a high barrier to resistance. C-Nucleosides have the potential for improved metabolism and pharmacokinetic properties over their N-nucleoside counterparts due to the presence of a strong carbon-carbon glycosidic bond and a non-natural heterocyclic base. Three 2'CMe-C-adenosine analogues and two 2'CMe-guanosine analogues were synthesized and evaluated for their anti-HCV efficacy.

Antiviral agents 3. Discovery of a novel small molecule non-nucleoside inhibitor of hepatitis B virus (HBV).

The discovery of a small molecule non-nucleoside inhibitor of Hepatitis B Virus is described. During our work on conocurvone derived naphthoquinone 'trimers' for the treatment of HIV, we discovered a potent inhibitor 9 of Hepatitis B Virus in an antiviral screen. During attempts to resynthesis 9 for proof of concept studies, we altered the synthesis in order to attempt to reduced side reactions and difficult to remove by-products.

Translational isomerism and dynamics in multi-hydroquinone derived porphyrin [2]- and [3]-catenanes.

A series of porphyrins strapped with polyether chains containing two or three 1,4-dioxybenzene units has been synthesised with a view to the production of porphyrin-containing [2] and [3]catenanes, where the porphyrin is strapped between ortho-positions of 5,15-(meso)-diaryl groups, and is interlinked with the bipyridinium macrocycle cyclobis(paraquat-4,4'-biphenylene). The porphyrins were isolated as mixtures of atropisomers, where the linking strap spans across the face of the porphyrin (alpha,alpha-isomer), or 'twisted' around its side (alpha,beta-isomer). Their structures were determined by detailed 1H NMR spectroscopy.

Photoinduced electron transfer between the interlocked components of porphyrin catenanes: effect of the presence of nonequivalent reduction sites on the charge recombination rate.

[2]Catenanes made up of several polyether-strapped porphyrin macrocycles interlinked with the cyclic electron acceptor cyclobis(paraquat-p-phenylene) were spectroscopically, photophysically, and electrochemically characterized. The catenanes exhibit very rich redox behavior due to the presence of several different and interacting electro-active subunits. The redox patterns represent useful "fingerprints" that provide detailed information on the electronic interactions and the chemical environments that the electroactive subunits experience in the supramolecular arrays.