Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain.
Eur J Med Chem
; 97: 245-58, 2015 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-25984841
ABSTRACT
Metabotropic glutamate receptor 1 (mGluR1) has been a prime target for drug discovery due to its heavy involvement in various brain disorders. Recent studies suggested that mGluR1 is associated with chronic pain and can serve as a promising target for the treatment of neuropathic pain. In an effort to develop a novel mGluR1 antagonist, we designed and synthesized a library of compounds with tetrahydrothieno[2,3-c]pyridine scaffold. Among these compounds, compound 9b and 10b showed excellent antagonistic activity in vitro and demonstrated pain-suppressing activity in animal models of pain. Both compounds were orally active, and compound 9b exhibited a favorable pharmacokinetic profile in rats. We believe that these compounds can provide a promising lead compound that is suitable for the potential treatment of neuropathic pain.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Receptores de Glutamato Metabotrópico
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Modelos Animais de Doenças
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Descoberta de Drogas
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Analgésicos
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Neuralgia
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Nitrilas
Tipo de estudo:
Evaluation_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2015
Tipo de documento:
Article