Example 39
Generally, pharmacophores for FAAH inhibitors, urea and non-urea based, interact by either carbamoylating or forming transition-state mimics with the catalytic serine residue. However, since a large number of hydrolases utilize a similar catalytic serine residue, many FAAH inhibitors have suffered from poor selectivity. Therefore, the potency of t-TUCB, A-14 and A-21 on several other serine hydrolases was tested. Included in this panel were carboxylesterases, hydrolases involved in xenobiotic detoxification, and paraoxonases and esterases involved in the regulation of arterosclerosis. As is shown in Table 5 below, none of these serine hydrolases were inhibited by t-TUCB, A-14, or A-21.
