N-(4-chloropyridin-3-yl)-4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)Methyl)piperazine-1-carboxaMide

Description

JNJ-42165279 is a potent, irreversible inhibitor of fatty acid amide hydrolase (FAAH; IC₅₀s = 70 and 313 nM for human and rat forms, respectively). It displays selectivity for FAAH over a panel of other enzymes, receptors, transporters, and ion channels. JNJ-42165279 is active in vivo, blocking FAAH activity in brain and periphery of rats and raising concentrations of anandamide , oleoyl ethanolamide , and palmitoyl ethanolamide . It is also efficacious in the spinal nerve ligation model of neuropathic pain.

in vitro

jnj-42165279 inhibited recombinant human and rat faah with the ic50s of 70 ± 8 nm and 313 ± 28 nm, respectively [1]. jnj-42165279 (10 μm) exhibited high selectivity against a panel of receptors, enzymes, transporters, and ion-channels. jnj-42165279 (10 μm) showed no inhibitory effects against cyps (1a2, 2c8, 2c9, 2c19, 2d6, 3a4) or herg [1].

in vivo

in the rat spinal nerve ligation (snl or chung) model of neuropathic pain, jnj-42165279 exhibited analgesic properties. jnj-42165279 dose-dependently reversed the robust tactile allodynia. the ed90 was 22 mg/kg, which corresponds to a plasma concentration of 2.5 μm at 30 min [1].

References

[1] keith j m, jones w m, tichenor m, et al. preclinical characterization of the faah inhibitor jnj-42165279[j]. acs medicinal chemistry letters, 2015, 6(12): 1204-1208.