Lamivudine antiviral agents

In their synthesis of the antiviral agent lamivudine 82, Rayner et al. employed the Pummerer rearrangement to form the a-acetoxysulphide 80. Treating 80 with HCl in dry ethanol then instigated transesterification thus causing removal of the acetate and subsequent in situ cyclization to the oxathialane 81, The authors note that heating the sulphoxide (120 °C) in the absence of NaOAc led to the formation of an enol ether by loss of ethanol. 

Lamivudine (also known as Epivir and 3TC) is a potent antiviral drug used in the treatment of HIV and hepatitis B virus (HBV) infections. Although both enantiomers are equipotent antiviral agents, the unnatural enantiomer (with respect to natural nucleosides) is far less cytotoxic, and so a method of selectively accessing the single enantiomer was required. 

Interferon alfa should typically be used in combination with antiviral agents such as lamivudine or adefovir dipivoxil (refer to BNF), the first-line treatment... 

Relapse Reactivation is often associated with the presence of wildtype HBV (80-85%) or the occurrence of precore mutants (15-20%). This event (increase of transaminases, evidence of replication markers such as HBeAg and HBV DNA, positive IgM anti-HBC, pronounced interface hepatitis) develops in 15-20% of cases 1-3 years after IFNa therapy has been stopped. In such cases the question then arises of whether to apply lamivudine. This antiviral agent is administered in cases with an unfavourable constellation or contraindication regarding IFNa, or if the patient refuses IFN. 

Lamlvudlne [an antiviral agent with potent activity against AIDS and hepatitis B virus] based MIPs were prepared and applied as sorbent in MISPE of Lamivudine in the biological fluids [human... 

MECHANISMS OE ACTION AND RESISTANCE Lamivudine triphosphate potently inhibits the DNA polymerase/reverse transcriptase of HBV. Lamivudine has enhanced antiviral activity against hepadnaviruses when combined with adefovir or penciclovir. Point mutations in the HBV DNA polymerase markedly reduce sensitivity. Lamivudine resistance confers cross-resistance to agents such as emtricitabine and is often associated with an additional mutation that confers cross-resistance to famciclovir. Lamivudine-resistant HBV retains susceptibility to adefovir and partially to entecavir. Viruses bearing certain mutations are less replication competent than wild-type HBV, but lamivudine resistance is associated with elevated HBV DNA levels, decreased likelihood of HbeAg loss or seroconversion, hepatitis exacerbations, and progressive fibrosis and graft loss in transplant recipients. 

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