1.
Bioorg Med Chem Lett
; 23(21): 6001-3, 2013 Nov 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-24050887
RESUMO
A novel series of benzimidazolone-containing histamine H3-receptor antagonists were prepared and their structure-activity relationship was explored. These benzimidazolone analogs demonstrate potent H3-receptor binding affinities, no P450 enzyme inhibition, and strong H3 functional activity. Compound 1o exhibits the best overall profile with H3Ki=0.95nM and rat AUC=12.9µMh.
Assuntos
Benzimidazóis/química , Benzimidazóis/farmacologia , Antagonistas dos Receptores Histamínicos H3/química , Antagonistas dos Receptores Histamínicos H3/farmacologia , Animais , Benzimidazóis/síntese química , Benzimidazóis/farmacocinética , Sistema Enzimático do Citocromo P-450/metabolismo , Cobaias , Antagonistas dos Receptores Histamínicos H3/síntese química , Antagonistas dos Receptores Histamínicos H3/farmacocinética , Humanos , Ratos , Receptores Histamínicos H3/metabolismo , Relação Estrutura-Atividade
2.
Bioorg Med Chem Lett
; 16(4): 989-94, 2006 Feb 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-16297617
RESUMO
A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory profiles has been identified. Structural features responsible for the reduction of P450 activity, a typical liability of 4-substituted imidazoles, have been established.
