Design, synthesis, evaluation and QSAR analysis of N(1)-substituted norcymserine derivatives as selective butyrylcholinesterase inhibitors

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1718-20. doi: 10.1016/j.bmcl.2010.01.057. Epub 2010 Jan 20.

Abstract

We synthesized a series of N(1)-substituted norcymserine derivatives 7a-p and evaluated their anti-cholinesterase activities. In vitro evaluation showed that the pyridinylethyl derivatives 7m-o and the piperidinylethyl derivative 7p improved the anti-butyrylcholinesterase activity by approximately threefold compared to N(1)-phenethylnorcymserine (PEC, 2). A quantitative structure-activity relationship (QSAR) study indicated that logS might be a key feature of the improved compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Butyrylcholinesterase / chemistry*
  • Butyrylcholinesterase / metabolism
  • Carbamates / chemical synthesis*
  • Carbamates / chemistry
  • Carbamates / pharmacology
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Drug Design
  • Humans
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Physostigmine / analogs & derivatives*
  • Physostigmine / chemistry
  • Quantitative Structure-Activity Relationship

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Physostigmine
  • Acetylcholinesterase
  • Butyrylcholinesterase