Norbenzomorphan Framework as a Novel Scaffold for Generating Sigmaâ
2 Receptor/PGRMC1 Subtype-Selective Ligands.
ChemMedChem
; 11(6): 556-61, 2016 Mar 17.
Article
en En
| MEDLINE
| ID: mdl-26915462
ABSTRACT
A novel structural class with high affinity and subtype selectivity for the sigma 2 receptor has been discovered. Preliminary structure-affinity relationship data are presented showing that 8-substituted 1,3,4,5-tetrahydro-1,5-methanobenzazepine (norbenzomorphan) derivatives elicit modest to high selectivity for the sigma 2 over the sigma 1 receptor subtype. Indeed, piperazine analogue 8-(4-(3-ethoxy-3-oxopropyl)piperazin-1-yl)-1,3,4,5-tetrahydro-1,5-methanobenzazepine-2-carboxylate (SAS-1121) is 574-fold selective for the sigma 2 over the sigma 1 receptor, thereby establishing it as one of the more subtype-selective sigma 2 binding ligands reported to date. Emerging evidence has implicated the sigma 2 receptor in multiple health disorders, so the drug-like characteristics of many of the selective sigma 2 receptor ligands disclosed herein, coupled with their structural similarity to frameworks found in known drugs, suggest that norbenzomorphan analogues may be promising candidates for further development into drug leads.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Benzazepinas
/
Benzomorfanos
/
Receptores de Progesterona
/
Receptores sigma
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos