RESUMEN

Optimisation of a novel series of osteoclast ATPase inhibitors led to (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6- pentamethylpiperidin-4-yl)-2,4-pentadienamide (1) that was the most potent compound in an in vitro osteoclast ATPase assay and in human bone resorption assays. Two of the possible geometric isomers have also been prepared and shown to be significantly less potent than 1.

Asunto(s)

Inhibidores Enzimáticos/farmacología , Osteoclastos/efectos de los fármacos , ATPasas de Translocación de Protón/antagonistas & inhibidores , ATPasas de Translocación de Protón Vacuolares , Inhibidores Enzimáticos/química , Humanos , Indoles/química , Indoles/farmacología , Isomerismo , Osteoclastos/enzimología , Piperidinas/química , Piperidinas/farmacología