Synthesis and anti-HIV evaluation of hybrid-type prodrugs conjugating HIV integrase inhibitors with d4t by self-cleavable spacers containing an amino acid residue.
J Enzyme Inhib Med Chem
; 22(5): 608-19, 2007 Oct.
Article
en En
| MEDLINE
| ID: mdl-18035829
ABSTRACT
In an attempt to combine the anti-HIV inhibitory capacity of reverse transcriptase (RT) inhibitors (NRTIs) and integrase (IN) inhibitors (INIs), several heterodimer analogues of the previously reported [d4T]-PABC-[INI] and [d4T]-OABC-[INI] prototypes have been prepared. In these novel series, we wished to extend our results to conjugates which incorporated an enzymatically labile aminoacid unit (L-alanine) connected to d4T through a self-immolative para- or ortho-aminobenzyl carbonate (PABC or OABC) spacer. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable to that of the [L-708,906]-PABC-[d4T] Heterodimer A prototype. However, although the compounds proved inhibitory to HIV-1, they were less potent than the parent compounds from which they were derived.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Profármacos
/
VIH
/
Estavudina
/
Inhibidores de la Transcriptasa Inversa
/
Inhibidores de Integrasa VIH
/
Fármacos Anti-VIH
/
Alanina
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Francia