The application of both structure- and ligand-based design approaches represents to date one of the most useful strategies in the discovery of new drug candidates. In the present paper, we investigated how the application of docking-driven conformational analysis can improve the predictive ability of 3D-QSAR statistical models. With the use of the crystallographic structure in complex with the high affinity antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol), we revisited a general pharmacophore hypothesis for the human A2A adenosine receptor of a set of 751 known antagonists, by applying an integrated ligand- and structure-based approach. Our novel pharmacophore hypothesis has been validated by using an external test set of 29 newly synthesized human adenosine receptor antagonists.

Revisiting a Receptor-Based Pharmacophore Hypothesis for Human A2A Adenosine Receptor Antagonists

TALIANI, SABRINA;DA SETTIMO PASSETTI, FEDERICO;
2013

Abstract

The application of both structure- and ligand-based design approaches represents to date one of the most useful strategies in the discovery of new drug candidates. In the present paper, we investigated how the application of docking-driven conformational analysis can improve the predictive ability of 3D-QSAR statistical models. With the use of the crystallographic structure in complex with the high affinity antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol), we revisited a general pharmacophore hypothesis for the human A2A adenosine receptor of a set of 751 known antagonists, by applying an integrated ligand- and structure-based approach. Our novel pharmacophore hypothesis has been validated by using an external test set of 29 newly synthesized human adenosine receptor antagonists.
Magdalena, Bacilieri; Antonella, Ciancetta; Silvia, Paoletta; Stephanie, Federico; Sandro, Cosconati; Barbara, Cacciari; Taliani, Sabrina; DA SETTIMO PASSETTI, Federico; Ettore, Novellino; Karl Norbert, Klotz; Giampiero, Spalluto; Stefano, Moro
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/218526
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