Nucleoside

Abstract: Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.

Abstract: Oligonucleoside alkyl-- or aryl phosphonates are nonionic analogues of nucleic acid which possess unique physical and biological properties. These properties enable the analogues to enter living cells intact and to bind with specifically selected nucleic acids within the cell. As a result, the analogues can specifically inhibit the function or expression of a preselected nucleic acid sequence. Thus the analogues could be used to specifically inhibit the growth of tumor cells or replication of viruses in infected cells. Four methods are provided for preparing oligonucleoside methylphosphonates: (1) Coupling a protected nucleoside 3'-alkyl or aryl phosphonate with the 5'-hydroxyl group of a protected nucleoside using a condensing agent; (2) Coupling protected nucleoside 3'-alkyl or aryl phosphonic acid derivative with the 5'-hydroxy group of a protected nucleoside with the activated alkyl or aryl phosphonic acid derivative possessing functionalities which are good leaving groups; (3) Coupling a protected nucleoside 3'-alkyl or aryl phosphinate derivative with the 5'-hydroxyl group of a protected nucleoside with the resulting phosphinate derivative being then oxidized to the phosphonate; and (4) Converting a oligonucleoside methoxyphosphite derivative to the alkyl or aryl phosphonate derivative by reaction with an alkyl or aryl iodide. It has been demonstrated that procedures (1) and (2) can be used to prepare oligonucleoside methylphosphonates. Others have shown that procedure (4) can be used to prepare a diribonucleoside methylphosphonate.