Synthesis and anti-HIV activity of some haloalkyl phosphoramidate derivatives of 3'-azido-3'-deoxythymidine (AZT): potent activity of the trichloroethyl methoxyalaninyl compound.
Phosphate triester derivatives of AZT have been prepared as membrane-soluble pro-drugs of the bio-active nucleotides, and have been evaluated against HIV-1 in vitro. In particular, the phosphorus centre carries a trichloro- or trifluoroethyl group and a carboxyl-protected, amino-linked amino acid. The compounds are prepared using phosphorochloridate chemistry, and are characterized by a range of techniques. They display potent anti-HIV activity and low host toxicity, but surprisingly this activity does not increase on the introduction of the haloalkyl moiety. The trichloroethyl methoxyalaninyl compound is exceptional: here the activity is enhanced 50-fold by the introduction of the trichloroethyl group.
McGuigan
C
C
Department of Chemistry, University of Southampton, Highfield, U.K.
Devine
K G
KG
O'Connor
T J
TJ
Kinchington
D
D
D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D015215:Zidovudine