Preparation, in vitro screening and molecular modelling of symmetrical 4-tert-butylpyridinium cholinesterase inhibitors--analogues of SAD-128

Bioorg Med Chem Lett. 2011 Jan 1;21(1):150-4. doi: 10.1016/j.bmcl.2010.11.051. Epub 2010 Nov 16.


Carbamate inhibitors (e.g., pyridostimine bromide) are used as a pre-exposure treatment for the prevention of organophosphorus poisoning. They work by blocking acetylcholinesterase's (AChE) native function and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, carbamate inhibitors are known for many undesirable side-effects related to the carbamylation of AChE. In this Letter, 19 analogues of SAD-128 were prepared and evaluated as cholinesterase inhibitors. The screening results showed promising inhibitory ability of four compounds better to used standards (pralidoxime, obidoxime, BW284c51, ethopropazine, SAD-128). Four most promising compounds were selected for further molecular docking studies. The SAR was stated from obtained data. The former receptor studies were reported and discussed. The further in vivo studies were recommended in the view of OP pre-exposure treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Acetylcholinesterase / metabolism
  • Binding Sites
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Computer Simulation
  • Models, Molecular
  • Organophosphates / chemistry
  • Pyridinium Compounds / chemical synthesis
  • Pyridinium Compounds / chemistry*
  • Pyridinium Compounds / pharmacology
  • Structure-Activity Relationship


  • Cholinesterase Inhibitors
  • Organophosphates
  • Pyridinium Compounds
  • SAD-128
  • Acetylcholinesterase