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-1 activity in PBMCs was determined. The methyl amides were more potent (EC50s = 1.8-4.0 microM) than the methyl esters (EC50s = 2.0-20 microM). Carbamate hydrolysis by cell lysates and liberation of AZT was not observed for representative methyl ester or methyl amide AZT carbamates. No evidence of direct inhibition of HIV reverse transcriptase or integrase was observed.
Chang
S L
SL
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
Griesgraber
G
G
Abraham
T W
TW
Garg
T
T
Song
H
H
Zimmerman
C L
CL
Wagner
C R
CR
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004355:Drug Stability; D015497:HIV-1; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D002219:Carbamates; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine