Diamine-based human histamine H3 receptor antagonists: (4-aminobutyn-1-yl)benzylamines.
Eur J Med Chem
; 44(10): 4098-106, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19524331
ABSTRACT
A series of (4-aminobutyn-1-yl)benzylamines were prepared and the SAR around three key areas (1) the amine attached to the butynyl linker (R(3)R(4)N-); (2) the benzylamine moiety (R(1)R(2)N-); and (3) the point of attachment of the benzylamine group (R(1)R(2)N- in the ortho, meta, or para positions) was examined. One compound, 4-[3-(4-piperidin-1-yl-but-1-ynyl)-benzyl]-morpholine (9s) was chosen for further profiling and found to be a selective histamine H(3) antagonist with desirable drug-like properties. Ex vivo receptor occupancy studies established that 9s does occupy H(3) binding sites in the brain of rats after oral administration. Subcutaneous doses of 9s (10mg/kg) given during the natural sleep phase demonstrated robust wake-promoting effects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sono
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Benzilaminas
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Receptores Histamínicos H3
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Antagonistas dos Receptores Histamínicos H3
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article