A variety of substituted 5′-N-phthaloyl-3′-azido-2′,3′-dideoxythymidine derivatives has been evaluated for their activity against HIV-1, HIV-2 and Moloney murine sarcoma virus (MSV) in cell culture. Most of the 3′-azido-2′,3′-dideoxythymidine (AZT, zidovudine) derivatives showed antiviral activity in the lower micromolar concentration range and there was a close correlation between their anti-HIV and anti-MSV activity (r=0.99). The adamantyl phthaloyl derivative was active at sub-micromolar concentrations. None of the compounds showed marked cytostatic activity. They did not inhibit recombinant HIV-1 reverse transcriptase. All compounds were inactive against HIV in thymidine kinase-deficient cells, pointing to the compounds' requirement to release free AZT to afford antiviral efficacy.
BalzariniJHerdewijnPPauwelsRBroderSDe ClercqE (1988) α,β- and β,γ-methylene 5′-phosphonate derivatives of 3′-azido-2′,3′-dideoxythymidine-5′-triphosphate. Biochemical Pharmacology37: 2395–2403.
2.
BalzariniJNaesensLSlachmuyldersJNiphuisHRosenbergIHolyASchellekensHDe ClercqE (1991) 9-(2-Phosphonyl-methoxyethyl)adenine (PMEA) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys. AIDS5: 21–28.
3.
De ClercqE (2002) Strategies in the design of antiviral drugs. Nature Reviews Drug Discovery1: 13–25.
4.
De ClercqEMeriganTC (1971) Moloney sarcoma virus-induced tumors in mice: Inhibition or stimulation by (poly rI).poly(rC). Proceedings of the Society for Experimental Biology and Medicine137: 590–594.
5.
HashimotoY (1998) Novel biological response modifiers derived from thalidomide. Current Medicinal Chemistry5: 163–178.
6.
KolocourisNKolocourisAFoscolosGBFytasGNeytsJPadalkoEBalzariniJSnoeckRGracielaADe ClercqE (1996) Synthesis and antiviral activity evaluation of some new aminoadamantane derivatives 2. Journal of Medicinal Chemistry39: 3307–3318.
7.
LanglerDWeiszK (2001) Novel phthalimide nucleosides for specific recognition of CG Watson-Crick base pair. Tetrahedron Letters42: 1479–1481.
8.
MeierC (1998) Pro-nucleotides — Recent advances in the design of efficient tools for the delivery of biologically active nucleoside monophosphates. Synletters, 233–242.
9.
MitsunobuO (1981) The use of diethyl azodicarboxylate and triph-enylphosphine in synthesis and transformation of natural products. Synthesis1–28.
10.
MiyachiHOgasawaraAAzumaAHasimotoY (1997) Tumor necrosis factor-alpha production-inhibiting activity of phthalimide analogues on human leukemia THP-1 cells and structure activity relationship study. Bioorganical & Medicinal Chemistry5: 2095–2102.
11.
OrzeszkoAKaminskaBOrzeszkoGStarosciakBJ (2000) Synthesis and antibacterial activity of new adamantane derivatives II. Il Farmaco55: 619.
12.
OrzeszkoAMaurinJKMelon-KsytaD (2001) Investigation of the thionation reaction of cyclic imides. Zeitschrift für Naturforschung56b: 1035–1040.
13.
OrzeszkoAKaminskaBStarosciakBJ (2002) Synthesis and antibacterial activity of new adamantane derivatives III. Il Farmaco57: 619.
14.
ParangKWiebeLIKnausEE (2000) Novel approaches for designing 5′-O-ester prodrugs of AZT. Current Medicinal Chemistry7: 995–1039.
15.
PelemansHEsnoufRMinK-LParniakMDe ClerqEBalzariniJ (2001) Mutations at amino acid positions 63, 189, and 396 of human immunodeficiency virus type 1 reverse transcriptase (RT) partially restore the DNA polymerase activity of a TRP229TYR mutant RT. Virology287: 143–250.
16.
SamantaSPainADuttaSSanyalU (2001) Synthesis and evaluation of 2-chloroethylnitrosoureas of substituted naphthalimides as mixed function anticancer compounds. Acta Poloniae Pharmaceutica-Drug Research58: 351–358.
17.
ShibataYSasakiKHashimotoYIwasakiS (1998) Tumor necrosis factor alpha production enhancers with a phenylphthalimide skeleton. Biochemical and Biophysical Research Communications205: 1992–1997.
