Dideoxynucleoside precursors

Recently, lamivudine [LAM ih vue deen] or (-)-2 -deoxy-3 -thiacyti-dine (3TC) has been approved for treatment of HIV in combination with zidovudine. This dideoxynucleoside terminates the synthesis of the proviral DNA chain and also inhibits reverse-transcriptase of both HIV and hepatitis B virus (HBV). However, it does not affect mitochondrial DNA synthesis or bone marrow precursor cells. Resistance to zidovudine develops more slowly with the combination. Lamivudine has good bioavailability on oral administration and depends on the kidney for excretion. Though generally well tolerated, pancreatitis develops in a significant number of pediatric... 

The precursor for the synthesis of the anti-HIV inactive compound, 2-iododideoxy-adenosine, 7 (Scheme 4), was the 2-amino-6-chloropurine 2 ,3 -dideoxynucleoside, 5 Compound 5 and its 5 -derivatives 6 (e.g., 5 -acylatcd) exhibit in vitro anti-HIV activity with ECjn values in the range of 5-10 pM. Compound 5 is a substrate for the enzyme, ADA, and the mechanism of its antiviral activity appears to be associated with its cellular conversion by ADA to ddG (Fig. 1). Several other prodrugs of ddG have also been synthesized by us. 

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