The most effective influence of 17-(3-ethoxypropyl) substituent on the binding affinity and the agonistic activity in KNT-127 derivatives, δ opioid receptor agonists.
Bioorg Med Chem
; 21(24): 7628-47, 2013 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-24262888
ABSTRACT
We investigated the structure-activity relationship of KNT-127 (opioid δ agonist) derivatives with various 17-substituents which are different in length and size. The 17-substituent in KNT-127 derivatives exerted a great influence on the affinity and agonistic activity for the δ receptor. While the compounds with electron-donating 17-substituents showed higher affinities for the δ receptor than those with electron-withdrawing groups, KNT-127 derivatives with 17-fluoroalkyl groups (the high electron-withdrawing groups) showed high selectivities for the δ receptor among evaluated compounds. In addition, the basicity of nitrogen as well as the structure of the 17-N substituent such as the length and configuration at an asymmetric carbon atom contributed to agonist properties for the δ receptor. Thus, the analog with a 17-(3-ethoxypropyl) group showed the best selectively and potent agonistic activity for the δ receptor among KNT-127 derivatives. These findings should be useful for designing novel δ selective agonists.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Opioides delta
/
Morfinanos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón