Synthesis of physostigmine analogues and evaluation of their anticholinesterase activities

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1532-4. doi: 10.1016/j.bmcl.2010.01.097. Epub 2010 Jan 25.

Abstract

A series of physostigmine analogues were prepared and evaluated for cholinesterase inhibition activities, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of them showed potent inhibition activities against AChE, in which compound 17 especially exhibited significantly higher selectivity over BChE than phenserine, a compound currently on clinical trial. Discussion about the relationships between structure and activity of these derivatives was also presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Acetylcholinesterase / metabolism
  • Animals
  • Butyrylcholinesterase / chemistry*
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Neurotransmitter Agents / chemical synthesis*
  • Neurotransmitter Agents / chemistry
  • Neurotransmitter Agents / pharmacology
  • Physostigmine / analogs & derivatives
  • Physostigmine / chemical synthesis*
  • Physostigmine / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Indoles
  • Neurotransmitter Agents
  • Physostigmine
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • phenserine