- TSAO derivatives: Highly specific inhibitors of human immunodeficiency virus type-1 (HIV-1) replication
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TSAO derivatives represent a unique class of nucleosides that are specifically targeted at HIV-1 RT. This overview is focussed on the chemical synthesis, the conformational studies, the antiviral and metabolic properties of TSAO derivatives, as well as th
- Camarasa,Perez-Perez,Velazquez,San-Felix,Alvarez,Ingate,Jimeno,Karlsson,De Clercq,Balzarini
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p. 585 - 594
(2007/10/02)
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- 3'-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: Synthesis and antiviral activity of [2',5'-bis-O-(tert- butyldimethylsilyl)-β-D-xylo- and -ribofuranose]-3'-spiro-5''-[4''-amino- 1'',2''-oxathiole 2'',2''-dioxide] (TSAO) pyrimidine nucleosides
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A series of 3'-spiro nucleosides have been synthesized and evaluated as anti-HIV-1 agents. Reaction of O-mesyl-cyanohydrins of furanos-3'-ulosyl nucleosides with base afforded [1,[2',5'-bis-O-(tert-butyldimethylsilyl)-β- D-xylo- and -ribofuranosyl]]-3'-spiro-5''-[4''-amino-1'',2''-oxathiole 2'',2''-dioxide] derivatives of thymine, uracil and 4-N-acetylcytosine 11 and 12. Desilylation of 11 and 12 gave the full deprotected 3'-spiro xylo- and ribofuranosyl nucleosides 13 and 14 or the partially 5'-O-deprotected-3'- spiro β-D-xylo- and -ribo-nucleosides 15 and 16, or 2'-O-deprotected-3'- spiro β-D-ribo-nucleoside 17. 2'-Deoxygenation of 17 afforded 2'-deoxy-3'- spiro β-D-erythro-pentofuranosyl derivative 18. These 3'-spiro derivatives were evaluated for their anti-HIV-1 activity. All 3'-spiro nucleosides having a xylo configuration did not show any anti-HIV-1 activity. 3'-Spiro ribo- nucleosides with none or only one silyl group at C-2' or C-5' or the 2'-deoxy derivative were also inactive at subtoxic concentrations. However, 3'-spiro ribo-nucleosides having two silyl groups at C-2' and C-5' were potent and selective inhibitors of HIV-1. None of the nucleoside analogues that showed anti-HIV-1 activity proved inhibitory to the replication of HIV-2 or SIV.
- Camarasa,Perez-Perez,San-Felix,Balzarini,De Clercq
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p. 2721 - 2727
(2007/10/02)
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- Synthesis of {1-[2',5'-bis-O-(t-butyldimethylsilyl)-β-D-xylo- and β-D-ribofuranosyl]Thymine}-3'-spiro-5''-{4''-amino-1'',2''-oxathiol e-2'',2''-dioxide} (TSAO). A novel type of specific anti-HIV agents
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Reaction of O-mesylcyanohydrins of furanos-3'-ulosyl thymine with bases afforded β-D-xylo- and ribo-3'-substituted nucleosides. 2'-Deoxygenation of the selectively 5'-O-protected nucleoside gave the ribofuranosyl derivative of thymidine.
- Perez-Perez,San-Felix,Camarasa,Balzarini,De Clercq
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p. 3029 - 3032
(2007/10/02)
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