(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

Bioorg Med Chem Lett. 1998 Dec 15;8(24):3621-6. doi: 10.1016/s0960-894x(98)00660-x.

Abstract

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.

MeSH terms

  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology
  • Isomerism
  • Osteoclasts / drug effects*
  • Osteoclasts / enzymology
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Proton-Translocating ATPases / antagonists & inhibitors*
  • Vacuolar Proton-Translocating ATPases*

Substances

  • Enzyme Inhibitors
  • Indoles
  • Piperidines
  • SB 242784
  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases