A rate determining step change in the pre-steady state of acetylcholinesterase inhibitions by 1,n-alkane-di-N-butylcarbamates

Bioorg Med Chem Lett. 2005 Feb 15;15(4):951-5. doi: 10.1016/j.bmcl.2004.12.058.

Abstract

Alkane-1-N-butylcarbamate-n-ols (1-7) and 1,n-alkane-di-N-butylcarbamates (8-14) are potent pseudo-substrate inhibitors of acetylcholinesterase. For inhibitors 1-7, the pre-steady state -logK(s) values and steady state -logK(i), values are linearly correlated with the tether length (N). However, for inhibitors 8-14, correlation of the -logK(s) or -logK(i) values against N deviates from linearity. A discontinuity of the -logK(s) versus N plot, concave downwards, is indicative of a rate determining step change in the pre-steady state of acetylcholinesterase inhibitions by inhibitors 8-14.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism*
  • Carbamates / chemical synthesis*
  • Carbamates / chemistry
  • Carbamates / pharmacology
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Humans
  • Kinetics
  • Models, Chemical

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Acetylcholinesterase