Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction power, whereas the diazabicyclononane was less effective. Biological data were rationalized through a computational study that allowed the conformational preferences of the compounds to be determined and a correlation between the inhibitory activity, the bridge length of the bicycle, and the rotational barrier around dihedral angle t7 to be hypothesized. A high-field NMR analysis supported the modeling results.

Diazabicyclo analogues of maraviroc: synthesis, modeling, NMR studies and antiviral activity

LEGNANI, LAURA;TOMA, LUCIO;
2017

Abstract

Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction power, whereas the diazabicyclononane was less effective. Biological data were rationalized through a computational study that allowed the conformational preferences of the compounds to be determined and a correlation between the inhibitory activity, the bridge length of the bicycle, and the rotational barrier around dihedral angle t7 to be hypothesized. A high-field NMR analysis supported the modeling results.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1177720
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