Nucleoside analog reverse transcriptase hepatitis

Compounds featuring this typical functionalized cyclopentane unit are the platelet aggregation inhibitor compound (1) of AstraZeneca, the HCV NS3 NS4A protease inhibitor (2) claimed by Tibotec for the treatment of Hepatitis C, and a Neuraminidase (Sialidase) inhibitor (3) discovered by Biocryst for the treatment of influenza (Figure 4.6). Likewise, the widely used nucleoside analog reverse transcriptase inhibitor Abacavir (4), administered against HIV, produced by GlaxoSmithKline, as well as Medivir s beta-secretase 1 (BACE 1) inhibitor (5) for the treatment of Alzheimer s dementia can be probably derived from this hydroformylation protocol. 

Mechanism of Action A guanosine nucleoside analog that inhibits hepatitis B viral polymerase, which blocks reverse transcriptase activity. Therapeutic Effect Interferes with viral DNA synthesis. 

Zalcitabine (2, 3 dideoxycytidine ddC) is a synthetic cytosine analog reverse-transcriptase inhibitor. It is active against HIV-I, HIV-2, and hepatitis B virus (HBV). The in vitro ICjo of zalcitabine against HIV-1 ranges from 2 nM in monocytes-macrophage cell lines to 0.5 pM in human peripheral blood mononuclear cells. Zalcitabine has considerably more antiretroviral activity in monocytes-macrophage cell lines than other nucleoside analogs, but the potential clinical utility of this observation is uncertain. 

Pharmacology Lamivudine is a synthetic nucleoside analog with activity against HIV and hepatitis B virus (HBV). Lamivudine is phosphorylated intracellularly to lamivudine 5 -triphosphate (L-TP). Incorporation of the monophosphate form into viral DMA by HBV polymerase results in DMA chain termination. L-TP also inhibits the RNA- and DNA-dependent DMA polymerase activities of HIV-1 reverse transcriptase. 

An example of the use of a terpene as a chiral auxiliary is provided by the synthesis of the anti-viral reverse transcriptase inhibitor Lamivudine (148). The nucleoside analog is marketed by Biochem Pharma (now Shire Pharmaceuticals) and Glaxo Wellcome (now GlaxoSmithKline) for the treatment of HIV and hepatitis B virus infection. In the... 

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