TSAO-T Analogues Bearing Amino Acids at Position N-3 of Thymine: Synthesis and Anti-Human Immunodeficiency Virus Activity

• Published in: Antiviral chemistry & chemotherapy 2000-01, Vol.11 (1), p.61-69
• Main Authors: Chamorro, C, De Clercq, E, Balzarini, J, Camarasa, M-J, San-Félix, A
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino acids; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Carboxylic acids; Cell Line; HIV; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Microbial Sensitivity Tests; Molecular Structure; nucleoside analogs; Pharmacology. Drug treatments; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; Thymidine - analogs & derivatives; Thymidine - chemical synthesis; Thymidine - chemistry; Thymidine - pharmacology; Thymine; Thymine - chemistry; Virus Replication - drug effects
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.1177/095632020001100106

Novel analogues of the anti-HIV-1 lead compound [1-[2‘,5’-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]thymine]-3‘-spiro-5’-(4“-amino-1”,2“-oxathiole-2‘,2’-dioxide) (TSAO-T) bearing different amino acids at position N-3 of thymine were prepared and evaluated as inhibitors of HIV replication. The synthesis of the target compounds was accomplished by coupling of the appropriate TSAO intermediate with a conveniently protected (L) amino acid in the presence of BOP and triethylamine, followed by depro-tection of the amino acid moiety. Several TSAO derivatives, bearing at N-3 position of the thymine base an L-amino acid retaining the free carboxylic acid, acquired activity against HIV-2, in addition to their inhibitory effect on HIV-1.