RESUMO
Asymmetric and symmetric spiro(imidazo[1,2-a]pyrano[2,3-c]pyridine-9-indenes) were prepared using a synthetic approach that comprised a cross-metathesis reaction and an acid-catalyzed cycloisomerisation as key steps. The target compounds constitute potent inhibitors of the gastric proton pump enzyme with inhibitory activity comparable to potassium-competitive acid blockers (P-CABs) belonging to the known 9-aryl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine series. Spiro(imidazo[1,2-a]pyrano[2,3-c]pyridine-9,2'-indenes) represent the first example for P-CABs, in which the distance between the heterocyclic scaffold and the aryl residue has been modified, and are promising candidates for further development as anti-ulcer drugs.
Assuntos
Antiulcerosos/síntese química , Ácido Gástrico/metabolismo , Imidazóis/síntese química , Imidazóis/farmacologia , Inibidores da Bomba de Prótons , Humanos , Indenos/síntese química , Indenos/farmacologia , Compostos de Espiro/síntese química , Compostos de Espiro/farmacologia , Relação Estrutura-AtividadeRESUMO
A series of novel 1H-pyrrolo[3,2-b]pyridines was prepared relying on a copper iodide catalyzed cyclization of 2-prop-1-ynylpyridin-3-amines. A structure-activity relationship was established focusing on the influence of the substitution pattern in position 1, 3, and 5 of the heterocycle on anti-secretory activity, lipophilicity, and pK(a) value. Some of the compounds proved to be potent inhibitors of the gastric acid pump.
Assuntos
Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Piridinas/síntese química , Piridinas/farmacologia , Pirróis/química , Animais , Estrutura Molecular , Piridinas/química , Coelhos , Relação Estrutura-AtividadeRESUMO
A series of novel 6-substituted imidazo[1,2-a]pyrazines were synthesized via palladium catalyzed amino- or alkoxycarbonylation as key step. The anti-secretory activity of these compounds has been assessed in a binding assay against H(+)/K(+)-ATPase from hog gastric mucosa. Some of the compounds proved to be potent inhibitors of the gastric acid pump.
Assuntos
Inibidores da Bomba de Prótons , Pirazinas/síntese química , Estômago/enzimologia , Animais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Pirazinas/farmacologia , SuínosRESUMO
A series of novel tetrahydroimidazo[2,1-a]isoquinolines was prepared based on a hetero Diels-Alder reaction between an enamine and 1,2,4-triazine as key step. A structure-activity relationship was established focussing on the influence of the substitution pattern in position 3 and 6 of the heterocycle on antisecretory activity, lipophilicity, and pK(a) value. Potent inhibitors of the gastric acid pump were identified.
Assuntos
Ácido Gástrico/metabolismo , Fármacos Gastrointestinais/síntese química , Fármacos Gastrointestinais/farmacologia , Isoquinolinas/síntese química , Inibidores da Bomba de Prótons , Avaliação Pré-Clínica de Medicamentos , Fármacos Gastrointestinais/química , Imidazóis , Isoquinolinas/química , Isoquinolinas/farmacologia , Estrutura Molecular , Bombas de Próton/efeitos dos fármacos , Estômago/efeitos dos fármacos , Relação Estrutura-Atividade , Triazinas/químicaRESUMO
A series of novel 8-indanylamino- and 8-indanyloxy-substituted imidazo[1,2-a]pyridines with reduced lipophilicity was synthesized from easily accessible starting compounds. The anti-secretory activity of these compounds has been assessed in a competitive binding assay against H(+)/K(+)-ATPase from hog gastric mucosa. Some of the compounds proved to be potent inhibitors of the gastric acid pump.