Synthesis and antiviral activity of amino acid carbamate derivatives of AZT

Lipophilic amino acid methyl ester and methyl amide carbamates of 3'-azido- 3'-deoxythymidine (AZT) were synthesized and their anti-HIV-l activity in P BMCs was determined. The methyl amides were more potent (EC(50)s = 1.8 - 4. 0 mu M) than the methyl esters (EC(50)s = 2.0 - 20 mu M). Carbamate hydroly sis by cell lysates and liberation of AZT was not observed for representati ve methyl ester or methyl amide AZT carbamates. No evidence of direct inhib ition of HIV reverse transcriptase or integrase was observed.