New conformationally locked bicyclic N,O-nucleoside analogues of antiviral drugs

1,3-Dipolar cycloadditions: applications to the synthesis of antiviral agents

“…The particular conformation of 39 reduces the probability of puckering interconversion, which justify strongly the conserved DNAlike shape and therefore they could be considered for optimisation studies for designing more potent HCV reverse 75 transcriptase inhibitors. 55 Phosphonated carboxylic-2'-oxa-3'-azanucleosides 40 were obtained according to the already mentioned thermal 1,3-DC. The nitrone-phosphonate and vinyl acetate followed by the attack of the purine or pyrimidine moiety to the anomeric carbon.…”

“…Compound 45 is in clinical phase due to its notable selectivity and potency against neuraminidase of a wide range of influenza A and B viruses. The strong 55 interaction between 45 and the S2 region of neuraminidase ensures a high inhibition. However, this agent may not confer ideal therapeutic characteristics due to several side effects.…”

“…The present and the future of these antiviral tools has 50 been reported since the pharmacological point of view of pathogenic specific drugs such as amantidine, Tamiflu ® , and Relenza ® or ribavirin and interferons targeted against influenza or hepatitis C viruses, respectively. 3 Unfortunately, extensive data on their efficacy are not available and recent 55 reports of drug resistance in patients infected with, for example, H5N1 raise serious concerns. 4 So, new broadspectrum antivirals must be developed because the cost and the risk to a rapid drug resistance of the antivirals targeted against single viruses are very elevated.…”

“…Although they are not considered antiviral agents, there are another contributions dealing with the synthesis of very interesting useful molecules for the study of biomolecular recognition, binding mecanisms, etc. For example, the 55 synthesis of radiolabelled peptides ( 18 F or 11 C), incorporating 1,2,3-triazole units, have been used as diagnostic agents, for example, as radiopharmaceuticals for several purposes, and also served as a vector to direct a small drug to the virus. 42 As well, azides and alkynes are easily transformed in the 60 corresponding 1,2,3-triazoles in the synthesis of ligands for the preparation of antiviral drugs, 43 in the preparation of sensors on oligo-or poly(ethylene glycol) films on silicon surfaces, which possessed an structural portion capable of being recognised by a biological specimen (included viruses), 44 and finally, in the elaboration of cross-linked polymeric multilayers, interesting for the fields of directed drug delivery towards viruses and tissue engineering.…”

“…These 3-methoxyarylamides had superior solubility properties and lower molecular weights than other precedent antiviral agents. In this occasion, to 55 resolve the racemic mixtures of compound 61, (R)-(−)-1,1'-binaphthyl-2,2'-diyl-hydrogen phosphate was employed providing the required diastereomeric salt in good yield and excellent enantiomeric excess at the end of the process (98.8%). In this work, a comparison of the X-ray structures of 60 dicarboxylic acid 55 and the binding site of the HCV polymerase was surveyed.…”