RESUMO
A series of N-[2-(dimethylamino)ethyl]-4-aryl-1-piperazinecarboxamides was synthesized and evaluated for antiallergy activity. Several derivatives had activity in the passive foot anaphylaxis (PFA) assay, an IgE-mediated model useful in the detection of compounds possessing antiallergic activity, but no derivative tested had activity at 10 mg/kg in the guinea pig anaphylaxis (GPA) assay. One analogue, N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)-1-piperazinecarboxamide , had an IC50 = 310 nM for inhibition of tritiated mepyramine binding to H1 histaminic receptors isolated from guinea pig cerebral cortex.
Assuntos
Dimetilaminas/síntese química , Antagonistas dos Receptores Histamínicos H1/síntese química , Piperazinas/síntese química , Anafilaxia , Animais , Dimetilaminas/uso terapêutico , Modelos Animais de Doenças , Cobaias , Imunoglobulina E , Indicadores e Reagentes , Estrutura Molecular , Piperazinas/uso terapêutico , Relação Estrutura-Atividade , Teofilina/uso terapêuticoRESUMO
A series of 4-(diarylhydroxymethyl)-1-[3-(aryloxy)propyl]piperidines was synthesized and evaluated for antiallergy activity. Several analogues had potent activity in the passive foot anaphylaxis (PFA) assay, an IgE-mediated model useful in the detection of compounds possessing antiallergic activity. In particular 1-[4-[3-[4-[bis(4-fluorophenyl)hydroxymethyl]-1-piperidinyl] propoxy]-3-methoxyphenyl]ethanone (1, AHR-5333) was more potent than oxatomide and terfenadine in this assay.
