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 τ7 to be hypothesized. A high-field NMR analysis supported the modeling results.

Diazabicyclo analogues of maraviroc : synthesis, modeling, NMR studies and antiviral activity / L. Legnani, D. Colombo, A. Venuti, C. Pastori, L. Lopalco, L. Toma, M. Mori, G. Grazioso, S. Villa. - In: MEDCHEMCOMM. - ISSN 2040-2503. - 8:2(2017 Feb), pp. 422-433. [10.1039/C6MD00575F]

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

D. Colombo;M. Mori;G. Grazioso;S. Villa
2017-02

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 τ7 to be hypothesized. A high-field NMR analysis supported the modeling results.
Settore CHIM/08 - Chimica Farmaceutica
16-dic-2016
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/463622
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