Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil

J Med Chem. 2001 Nov 8;44(23):4011-4. doi: 10.1021/jm0109356.

Abstract

The design, synthesis, and rapid evaluation of a new class of acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Donepezil
  • Drug Evaluation, Preclinical
  • Indans / chemistry*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Luminescent Measurements
  • Models, Molecular
  • Nootropic Agents / chemical synthesis*
  • Nootropic Agents / chemistry
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry*
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Structure-Activity Relationship

Substances

  • Indans
  • Indoles
  • Nootropic Agents
  • Piperidines
  • Pyrroles
  • Donepezil
  • Acetylcholinesterase