Structural modification of 5-alkyl-4-phenyl-thiazole-based fatty acid amide hydrolase and soluble epoxide hydrolase inhibitors to alleviate orofacial inflammatory pain in the rat

Highlights • Eleven 5-alkyl-4-phenylthiazole FAAH/sEH inhibitors were synthesized.• 4j showed potent dual inhibition of both enzymes (FAAH 18.7 nM; sEH 25.1 nM).• 4j reversed acute orofacial inflammatory pain in female rats with no motor effects.• This effect in vivo was comparable to the antinociception provided by sumatriptan.• 5-alkyl-4-phenylthiazole FAAH/sEH inhibitors may be useful to treat orofacial pain.