Details

Autor(en) / Beteiligte

• Basso, Elisa
• Duranti, Andrea
• Mor, Marco
• Piomelli, Daniele
• Tontini, Andrea
• Tarzia, Giorgio
• Traldi, Pietro

Titel

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

Ist Teil von

• Journal of mass spectrometry, 2004-12, Vol.39 (12), p.1450-1455

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (r2 = 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.