Synthesis and σ receptor affinity of regioisomeric spirocyclic furopyridines.
Eur J Med Chem
; 83: 709-16, 2014 Aug 18.
Article
en En
| MEDLINE
| ID: mdl-25016157
ABSTRACT
In order to investigate systematically the effect of the position of the pyridine N-atom on the σ1 receptor affinity four regioisomeric furopyridines 2a-d were synthesized and pharmacologically evaluated. The key steps of the synthesis comprise bromine/lithium exchange at regioisomeric bromopyridinecarbaldehyde acetals 7a-d, subsequent addition to 1-benzylpiperidin-4-one and cyclization. The regioisomeric acetals 7a-d were obtained either by o-metalation of bromopyridines 5b and 5c or by oxidation of bromopicolines 3a and 3d. In radioligand binding studies the regioisomeric furopyridines 2a-d showed 7- to 12-fold lower σ1 affinity than the benzofuran analog 1. The reduced σ1 affinity of the furopyridines 2a-d is explained with the reduced electron density of the pyridine ring. Since the four regioisomeric furopyridines show almost the same σ1 affinity (Ki = 4.9-10 nM), a directed interaction of the pyridine N-atom with the receptor protein can be excluded.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridinas
/
Compuestos de Espiro
/
Receptores sigma
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón