Synthesis of pentacyclic iminosugars with constrained butterfly-like conformation and their HIV-RT inhibitory activity.
Bioorg Med Chem Lett
; 28(3): 425-428, 2018 02 01.
Article
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| MEDLINE
| ID: mdl-29269212
ABSTRACT
Novel pentacyclic iminosugars 1 and 2 with the constrained butterfly-like conformation were first synthesized by the key intramolecular click reaction from the tricyclic iminosugars fused benzo[e][1,3]thiazin-4-one 3 and 4. The pentacyclic iminosugar was constructed by fusing both benzo[e][1,3]thiazin-4-one and triazolo[5,1-c][1,4]oxazepine scaffolds. Their structures were determined by their 1H, 13C NMR, and HRMS (ESI) spectra and X-ray. The pentacyclic iminosugars 1(a-c), 2(a-b) and their corresponding protected precursors 13(a-c) and 14(a-b) were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that all compounds could effectively inhibit RT activity. Among them, compound 13c was the best one with the IC50 value of RT inhibitory activity of 0.69⯵M. Structure-activity relationship analysis suggested that the improvement of the hydrophilicity of the pentacycles was of benefit to their anti-HIV RT activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de la Transcriptasa Inversa
/
Iminoazúcares
/
Transcriptasa Inversa del VIH
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China