RESUMO
A structure-activity relationship study of the lead piperazinylcarbonylpiperidine compound 3 resulted in the identification of 4-benzimidazolyl-piperidinylcarbonyl-piperidine 6h as a histamine-3 (H(3)) receptor antagonist. Additional optimization of 6h led to the identification of compounds 11i-k with K(i) Assuntos
Antagonistas dos Receptores Histamínicos H3/síntese química
, Antagonistas dos Receptores Histamínicos H3/farmacologia
, Piperidinas/síntese química
, Piperidinas/farmacologia
, Relação Estrutura-Atividade
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.