Revisiting a receptor-based pharmacophore hypothesis for human A(2A) adenosine receptor antagonists
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 A(2A) 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Journal of chemical information and modeling - 53(2013), 7 vom: 22. Juli, Seite 1620-37 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bacilieri, Magdalena [VerfasserIn] |
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| Links: |
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| Themen: |
Adenosine A2 Receptor Antagonists |
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| Anmerkungen: |
Date Completed 20.02.2014 Date Revised 22.07.2013 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/ci300615u |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM227773853 |
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| 520 | |a 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 A(2A) 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 | ||
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| 650 | 7 | |a Adenosine A2 Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Receptor, Adenosine A2A |2 NLM | |
| 650 | 7 | |a Triazines |2 NLM | |
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| 700 | 1 | |a Ciancetta, Antonella |e verfasserin |4 aut | |
| 700 | 1 | |a Paoletta, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Federico, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Cosconati, Sandro |e verfasserin |4 aut | |
| 700 | 1 | |a Cacciari, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Taliani, Sabrina |e verfasserin |4 aut | |
| 700 | 1 | |a Da Settimo, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Novellino, Ettore |e verfasserin |4 aut | |
| 700 | 1 | |a Klotz, Karl Norbert |e verfasserin |4 aut | |
| 700 | 1 | |a Spalluto, Giampiero |e verfasserin |4 aut | |
| 700 | 1 | |a Moro, Stefano |e verfasserin |4 aut | |
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