Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2.
Bioorg Med Chem Lett
; 23(13): 3857-63, 2013 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-23719231
ABSTRACT
Replacement of the dimethoxyphenyl moiety in the core skeleton of almorexant by appropriately substituted imidazoles afforded novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as potent dual orexin receptor antagonists. We describe in this Letter our efforts to further optimize the potency and brain penetration of these derivatives by fine-tuning of the pivotal phenethyl motif, and we comment on the sleep-promoting activity of selected compounds in a rat electroencephalographic (EEG) model.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrazines
/
Orexin Receptor Antagonists
/
Imidazoles
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Year:
2013
Document type:
Article