Potent acetylcholinesterase inhibitors: design, synthesis, and structure-activity relationships of bis-interacting ligands in the galanthamine series

Bioorg Med Chem. 1998 Oct;6(10):1835-50. doi: 10.1016/s0968-0896(98)00133-3.

Abstract

New galanthamine derivatives, especially bis-interacting ligands 3-5 and 7-9 were prepared in order to interact with the catalytic and the peripheral sites of acetylcholinesterase (AChE). The synthesis, the anticholinesterase activities, and the structure-activity relationships of bis-interacting ligands are reported. Compounds 4d-e were found to be more potent than galanthamine and tacrine in inhibiting AChE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects*
  • Acetylcholinesterase / metabolism
  • Benzazepines / chemistry*
  • Benzazepines / metabolism
  • Benzazepines / pharmacology*
  • Binding Sites
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Design
  • Galantamine / chemistry*
  • Phthalimides / chemistry*
  • Phthalimides / metabolism
  • Phthalimides / pharmacology*
  • Structure-Activity Relationship

Substances

  • 9-dehydro-10-N-demethyl--10-N-(10'-phthalimidodecyl)galanthaminium
  • 9-dehydro-10-N-demethyl-10-N-(8'-phthalimidooctyl)galanthaminium
  • Benzazepines
  • Cholinesterase Inhibitors
  • Phthalimides
  • Galantamine
  • Acetylcholinesterase