Identification of biaryl sulfone derivatives as antagonists of the histamine H3 receptor: discovery of (R)-1-(2-(4'-(3-methoxypropylsulfonyl)biphenyl-4-yl)ethyl)-2-methylpyrrolidine (APD916).
Bioorg Med Chem Lett
; 22(1): 71-5, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22172695
ABSTRACT
The design of a new clinical candidate histamine-H(3) receptor antagonist for the potential treatment of excessive daytime sleepiness (EDS) is described. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were modified by replacement of the sulfonamide linkage with a sulfone. One compound from this series, 2j (APD916) increased wakefulness in rodents as measured by polysomnography with a duration of effect consistent with its pharmacokinetic properties. The identification of a suitable salt form of 2j allowed it to be selected for further development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
/
Sulfonas
/
Compostos de Bifenilo
/
Receptores Histamínicos H3
/
Antagonistas dos Receptores Histamínicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article