Antiviral agents nucleoside reverse transcriptase

Hurwitz SJ, Schinazi RF (2002) Development of a pharmacodynamic model for HIV treatment with nucleoside reverse transcriptase and protease inhibitors. Antiviral Res 56 115-127 Hurwitz SJ, Tennant BC, Korba BE, Gerin JL, Schinazi RF (1998) Pharmacodynamics of (—)-beta-2, 3 -dideoxy-3 -thiacytidine in chronically virus-infected woodchucks compared to its pharmacodynamics in humans, Antimicrob Agents Chemother 42 2804-2809 Hurwitz SJ, Otto MJ, Schinazi RF (2005) Comparative pharmacokinetics of Racivir, (+/-)-beta-2, 3 -dideoxy-5-fluoro-3 -thiacytidine in rats, rabbits, dogs, monkeys and HIV-infected humans, Antivir Chem Chemother 16 117-127... 

The replicative cycle of HIV presents many opportunities for the targeting of antiviral agents. The drugs in clinical use are classified as nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NTRTIs), and protease inhibitors (PI). 

The sites at which anti-HIV drugs may. in principle, act, are dealt with in detail under a main heading (see ANTIVIRAL agents). In summary, currently, of the drugs actually in use, a number are reverse transcriptase (enzyme) inhibitors (RTIs). Examples of nucleoside RTIs include zidovudine, didanosine and zalcitabine. Some non-nucleoside RTIs include foscarnet sodium, nevirapine, carbovir and TIBO analogues (some of these are at trial stage only). 

Zagreb antivenom is a non-proprietary antivenom preparation that can be used as an injected ANTIDOTE to the poison from an adder s bite. However, the systemic allergic and other effects of the venom are rarely serious enough to warrant the use of the antivenom, zalcitabine [ban, inn, usan] (ddC DDC Hivid ) is a synthetic nucleoside analogue, a REVERSE TRANSCRIPTASE INHIBITOR which acts as an ANTIVIRAL AGENT. It is active orally as an ANTI-HIV AGENT. 

Nucleoside analogues are widely used as antiviral agents in the treatment in AIDS and AIDS-related complex. The only clinical agent approved in the United States for the treatment of AIDS is 3 -azido-3 -deoxythymidine (AZT) [54,55]. The molecular mechanism of action for this nucleoside includes conversion into its corresponding 5 -monophosphate by the action of cellular nucleoside kinase, followed by stepwise phosphorylation catalyzed by cellular nucleoside kinase to the corresponding 5 -triphosphate. These inhibit proviral DNA synthesis [55-57], catalyzed by HIV reverse transcriptase (RT), and incorporation to the 3 end of the growing DNA chain [55,58]. 

The enantiopure A-Ts cyclopentene carboxamide 35, obtained by a [2+2] cycloaddition and an enzymatic resolution, could also be a platform to synthesize the antiviral agent ( )-abacavir 38 (Scheme 41.8), which is a nucleoside analog reverse transcriptase inhibitor used in combination... 

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