Novel series of tunable µOR modulators with enhanced brain penetration for the treatment of opioid use disorder, pain and neuropsychiatric indications.
Bioorg Med Chem Lett
; 92: 129405, 2023 08 15.
Article
em En
| MEDLINE
| ID: mdl-37414346
ABSTRACT
Structural optimization of a previously reported agonist of µOR, PZM21 is described resulting in the discovery of a novel series of amides with at least 4-folds enhanced CNS penetration in rat. Furthermore, these efforts yielded compounds with varying levels of efficacy on the receptor ranging from high efficacy agonists such as compound 20 to antagonists, such as 24. The correlation between in vitro activation of µOR and relative activity in models of analgesia for these compounds is discussed. The compelling results obtained in these studies demonstrate the potential utility of these newly discovered compounds in the treatment of pain and opioid use disorder.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Transtornos Relacionados ao Uso de Opioides
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos