In a previous medicinal chemistry program aiming at improving PF-3845 for the treatment of inflammatory pain and other nervous system disorders, the kinetic parameter kinact/Ki for covalent inhibition of human FAAH increased from 12,600 M−1s−1 (PF-3845) to 40,300 M−1s−1 (PF-004457845) (41). Here, FAAH is linked to nervous system disorder.