1.
Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity.
Bioorg Med Chem Lett
; 22(4): 1546-9, 2012 Feb 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-22297111
RESUMO
Structure-activity relationship on a novel ketone class of H(3)R antagonists/inverse agonists is disclosed. Compound 4 showed excellent target potency, selectivity and brain penetration. Evaluation of antagonist 4 in the rat EEG/EMG model demonstrated robust wake activity thereby establishing preclinical proof of concept.
Assuntos
Agonistas dos Receptores Histamínicos/farmacologia , Cetonas/química , Morfolinas/química , Receptores Histamínicos H3 , Vigília/efeitos dos fármacos , Animais , Eletroencefalografia , Agonistas dos Receptores Histamínicos/química , Humanos , Cetonas/farmacologia , Masculino , Estrutura Molecular , Morfolinas/farmacologia , Ratos , Relação Estrutura-Atividade
2.
Eur J Med Chem
; 54: 949-51, 2012 Aug.
Artigo
em Inglês
| MEDLINE
| ID: mdl-22749190
RESUMO
In search of a next generation molecule to the novel wake promoting agent modafinil, a series of diphenyl ether derived wakefulness enhancing agents (in rat) was developed. From this work, racemic compound 16 was separated into its chiral enantiomers to profile them individually.