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Tandem mass spectrometric data-FAAH inhibitory activity relationships of some carbamic acid O-aryl esters

  • Author(s): Basso, E
  • Duranti, A
  • Mor, M
  • Piomelli, D
  • Tontini, A
  • Tarzia, G
  • Traldi, P
  • et al.

Published Web Location

https://doi.org/10.1002/jms.729Creative Commons Attribution 4.0 International Public License
Abstract

We have recently described a class of systemically active inhibitors of the intracellular activity of fatty acid amide hydrolase (FAAH) and traced extensive structure-activity relationships. These compounds, characterized by an N-alkyl carbamic acid O-aryl ester structure, exert potent anxiolytic-like effects in animal models. In the present study, possible relationships between mass spectrometric parameters (related to the propensity of the C(O)-O bond to be cleaved) and FAAH-inhibitory potency were tested. With this aim, a set of our products was analyzed by electrospray ionization mass spectrometry and the protonated molecules were decomposed by low-energy collisions. The experiments were performed by ion trap mass spectrometry, which led to a step-by-step energy deposition, thus favouring the lowest critical energy decomposition channels. For all compounds, breakdown curves relative to [MH]+ ions and to the fragment implying C(O)-O bond cleavage were obtained. The crossing point between these curves was related to the energetics of decomposition and the values found for the investigated compounds were linearly correlated (r 2 = 0.797) with their FAAH-inhibitory activity. This indicates that the energetics of the C(O)-O bond cleavage may be relevant in explaining FAAH inhibition. Copyright © 2004 John Wiley & Sons, Ltd.

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