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Titolo:
New 3 '-azido-3 '-deoxythymidin-5 '-yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs: Synthesis and anti-HIV evaluation
Autore:
Vlieghe, P; Clerc, T; Pannecouque, C; Witvrouw, M; De Clercq, E; Salles, JP; Kraus, JL;
Indirizzi:
Fac Sci Luminy, Lab Chim Biomol, F-13288 Marseille 9, France Fac Sci Luminy Marseille France 9 im Biomol, F-13288 Marseille 9, France Labs LAPHAL, F-13718 Allauch, France Labs LAPHAL Allauch France F-13718Labs LAPHAL, F-13718 Allauch, France Katholieke Univ Leuven, Med Res Inst, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 t, B-3000 Louvain, Belgium
Titolo Testata:
JOURNAL OF MEDICINAL CHEMISTRY
fascicolo: 18, volume: 44, anno: 2001,
pagine: 3014 - 3021
SICI:
0022-2623(20010830)44:18<3014:N3'''O>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; REVERSE-TRANSCRIPTASE INHIBITOR; IMMUNE-DEFICIENCY SYNDROME; PHOSPHOTRIESTER DERIVATIVES; AZIDOTHYMIDINE AZT; DOUBLE-BLIND; ZIDOVUDINE; INVITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Kraus, JL Fac Sci Luminy, Lab Chim Biomol, 163 Ave Luminy,Case 901, F-13288 Marseille 9, France Fac Sci Luminy 163 Ave Luminy,Case 901 Marseille France 9 rance
Citazione:
P. Vlieghe et al., "New 3 '-azido-3 '-deoxythymidin-5 '-yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs: Synthesis and anti-HIV evaluation", J MED CHEM, 44(18), 2001, pp. 3014-3021

Abstract

New 5 ' -O-carbonate prodrugs of zidovudine (AZT) have been synthesized inorder to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement processrelated to the 5 ' -O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement was confirmed by comparison of the serum half-lives of the 3 ' -azido-3 ' -deoxythymidin-5 ' -yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs with our thermodynamic predictions. Interestingly, these 5 ' -O-carbonate prodrug series show increased anti-HIV potencies in conjunction with, or without, reduced cytotoxicity as compared to AZT that lead to a gain in selectivity indexes. The cytotocity of AZT could be reduced with these 5 ' -O-carbonate prodrug series by delaying the 5' -O-glucuronidation of AZT, which is one of the major limitations of AZT.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 13:20:28