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 Locationhttps://doi.org/10.1002/jms.729
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.
Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.