(2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide, a novel, potent and selective inhibitor of the osteoclast V-ATPase

Optimisation of a novel series of osteoclast ATPase inhibitors led to (2Z,4 E)-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 vit ro osteoclast ATPase assay and in human bone resorption assays. Two of the possible geometric isomers have also been prepared and shown to be signific antly less potent than 1. (C) 1998 Elsevier Science Ltd. All rights reserve d.