Novel benzothiophene H1-antihistamines for the treatment of insomnia.
Bioorg Med Chem Lett
; 20(7): 2316-20, 2010 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-20188547
SAR of lead benzothiophene H(1)-antihistamine 2 was explored to identify backup candidates with suitable pharmacokinetic profiles for an insomnia program. Several potent and selective H(1)-antihistamines with a range of projected half-lives in humans were identified. Compound 16d had a suitable human half-life as demonstrated in a human microdose study, but variability in pharmacokinetic profile, attributed to metabolic clearance, prevented further development of this compound. Compound 28b demonstrated lower predicted clearance in preclinical studies, and may represent a more suitable backup compound.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tiofenos
/
Antagonistas de los Receptores Histamínicos H1
/
Trastornos del Inicio y del Mantenimiento del Sueño
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos