Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design

[Image: see text] Potent, ligand efficient, selective, and orally efficacious 1,2,4-triazine derivatives have been identified using structure based drug design approaches as antagonists of the adenosine A(2A) receptor. The X-ray crystal structures of compounds 4e and 4g bound to the GPCR illustrate...

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Autores principales: Congreve, Miles, Andrews, Stephen P., Doré, Andrew S., Hollenstein, Kaspar, Hurrell, Edward, Langmead, Christopher J., Mason, Jonathan S., Ng, Irene W., Tehan, Benjamin, Zhukov, Andrei, Weir, Malcolm, Marshall, Fiona H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2012
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308197/
https://www.ncbi.nlm.nih.gov/pubmed/22220592
http://dx.doi.org/10.1021/jm201376w
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author Congreve, Miles
Andrews, Stephen P.
Doré, Andrew S.
Hollenstein, Kaspar
Hurrell, Edward
Langmead, Christopher J.
Mason, Jonathan S.
Ng, Irene W.
Tehan, Benjamin
Zhukov, Andrei
Weir, Malcolm
Marshall, Fiona H.
author_facet Congreve, Miles
Andrews, Stephen P.
Doré, Andrew S.
Hollenstein, Kaspar
Hurrell, Edward
Langmead, Christopher J.
Mason, Jonathan S.
Ng, Irene W.
Tehan, Benjamin
Zhukov, Andrei
Weir, Malcolm
Marshall, Fiona H.
author_sort Congreve, Miles
collection PubMed
description [Image: see text] Potent, ligand efficient, selective, and orally efficacious 1,2,4-triazine derivatives have been identified using structure based drug design approaches as antagonists of the adenosine A(2A) receptor. The X-ray crystal structures of compounds 4e and 4g bound to the GPCR illustrate that the molecules bind deeply inside the orthosteric binding cavity. In vivo pharmacokinetic and efficacy data for compound 4k are presented, demonstrating the potential of this series of compounds for the treatment of Parkinson’s disease.
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spelling pubmed-33081972012-03-20 Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design Congreve, Miles Andrews, Stephen P. Doré, Andrew S. Hollenstein, Kaspar Hurrell, Edward Langmead, Christopher J. Mason, Jonathan S. Ng, Irene W. Tehan, Benjamin Zhukov, Andrei Weir, Malcolm Marshall, Fiona H. J Med Chem [Image: see text] Potent, ligand efficient, selective, and orally efficacious 1,2,4-triazine derivatives have been identified using structure based drug design approaches as antagonists of the adenosine A(2A) receptor. The X-ray crystal structures of compounds 4e and 4g bound to the GPCR illustrate that the molecules bind deeply inside the orthosteric binding cavity. In vivo pharmacokinetic and efficacy data for compound 4k are presented, demonstrating the potential of this series of compounds for the treatment of Parkinson’s disease. American Chemical Society 2012-01-05 2012-03-08 /pmc/articles/PMC3308197/ /pubmed/22220592 http://dx.doi.org/10.1021/jm201376w Text en Copyright © 2012 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Congreve, Miles
Andrews, Stephen P.
Doré, Andrew S.
Hollenstein, Kaspar
Hurrell, Edward
Langmead, Christopher J.
Mason, Jonathan S.
Ng, Irene W.
Tehan, Benjamin
Zhukov, Andrei
Weir, Malcolm
Marshall, Fiona H.
Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design
title Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design
title_full Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design
title_fullStr Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design
title_full_unstemmed Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design
title_short Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design
title_sort discovery of 1,2,4-triazine derivatives as adenosine a(2a) antagonists using structure based drug design
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308197/
https://www.ncbi.nlm.nih.gov/pubmed/22220592
http://dx.doi.org/10.1021/jm201376w
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