Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4).
ACS Chem Neurosci
; 7(9): 1192-200, 2016 09 21.
Article
em En
| MEDLINE
| ID: mdl-27075300
ABSTRACT
The efficacy of positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 4 (mGlu4) in preclinical rodent models of Parkinson's disease has been established by a number of groups. Here, we report an advanced preclinically characterized mGlu4 PAM, N-(3-chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506). We detail the discovery of VU0418506 starting from a common picolinamide core scaffold and evaluation of a number of amide bioisosteres leading to the novel pyrazolo[4,3-b]pyridine head group. VU0418506 has been characterized as a potent and selective mGlu4 PAM with suitable in vivo pharmacokinetic properties in three preclinical safety species.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ácidos Picolínicos
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Pirazóis
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Piridinas
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Receptores de Glutamato Metabotrópico
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Fármacos Atuantes sobre Aminoácidos Excitatórios
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article