Selective CB2 receptor agonists. Part 3: the optimization of a piperidine-based series that demonstrated efficacy in an in vivo neuropathic pain model.
Bioorg Med Chem Lett
; 25(3): 587-92, 2015 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-25575658
ABSTRACT
A novel class of potent cannabinoid receptor 2 (CB2) agonists based on a (S)-piperidine scaffold was identified using ligand-based pharmacophore models. Optimization of solubility and metabolic stability led to the identification of several potent CB2 agonists (e.g., 30) that displayed selectivity over cannabinoid receptor 1 (CB1) and acceptable drug like properties. In rats, compound 30 demonstrated a favorable pharmacokinetic profile and efficacy in a Streptozotocin-induced diabetic neuropathy model, with full reversal of mechanical hyperalgesia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Pipecólicos
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Piperidinas
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Tiazinas
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Receptor CB2 de Canabinoide
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article