1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine. A highly potent and selective anti-HIV agent
| Autor: | M M, Mansuri, J E, Starrett, I, Ghazzouli, M J, Hitchcock, R Z, Sterzycki, V, Brankovan, T S, Lin, E M, August, W H, Prusoff, J P, Sommadossi |
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| Rok vydání: | 1989 |
| Předmět: |
Nucleoside analogue
Stereochemistry HIV Antiviral Agents In vitro Reverse transcriptase Dideoxynucleosides Thymine chemistry.chemical_compound Stavudine chemistry Bone Marrow parasitic diseases Drug Discovery Toxicity medicine Molecular Medicine Anti-HIV Agent Primer (molecular biology) Beta-D Zidovudine medicine.drug Thymidine |
| Zdroj: | Journal of medicinal chemistry. 32(2) |
| ISSN: | 0022-2623 |
| Popis: | The nucleoside analogue 1-(2,3-dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine (d4T, 1) was prepared by ring opening of the 3',5'-anhydro compound 5. This method has been refined such that it can be used to prepare d4T on a large scale. The triphosphate of d4T was also synthesized from 1 in order to examine the mode of action. The in vitro inhibitory activity of d4T was found to be comparable to that of AZT in HIV-infected CEM cells. The triphosphate of d4T (8) and that of AZT inhibited the HIV reverse transcriptase with poly(rA):oligo(dT) as the template:primer with Ki values of 0.032 and 0.007 microM, respectively. The in vitro toxicity of d4T against normal human hematopoietic progenitor cells (CFU-GM) was measured in comparison to AZT. While d4T reduces colony-forming units by 50% at a concentration of 100 microM, it takes only 1 microM AZT to have a similar toxic effect. With erythrocyte burst forming units (BFU-E) the in vitro toxicities for d4T and AZT have comparable ID50 values of 10 and 6.7 microM, respectively. |
| Databáze: | OpenAIRE |
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