Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands.
J Med Chem
; 48(6): 1781-95, 2005 Mar 24.
Article
en En
| MEDLINE
| ID: mdl-15771424
ABSTRACT
Based on a medicinal chemistry guided hypothetical pharmacophore model, novel series of indolyl sulfonamides have been designed and prepared as selective and high-affinity serotonin 5-HT(6) receptor ligands. Furthermore, based on a screening approach of a discovery library, a series of benzoxazinepiperidinyl sulfonamides were identified as selective 5-HT(6) ligands. Many of the compounds described in this paper possess excellent affinities, displaying pK(i) values greater than 8 (some even >9) and high selectivities against a wide range (>50) of other CNS relevant receptors. First, structure-affinity relationships of these ligands are discussed. In terms of functionality, high-affinity antagonists, as well as agonists and even partial agonists, were prepared. Compounds 19c and 19g represent the highest-affinity 5-HT(6) agonists ever reported in the literature. These valuable tool compounds should allow for the detailed study of the role of the 5-HT(6) receptor in relevant animal models of disorders such as cognition deficits, depression, anxiety, or obesity.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antagonistas de la Serotonina
/
Sulfonamidas
/
Receptores de Serotonina
/
Agonistas de Receptores de Serotonina
/
Indoles
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
España