Discovery of a novel class of benzoxazole derivatives as histamine H3 receptor ligands for the treatment of neuropathic pain

•A series of benzoxazole derivatives were designed and synthesized as H3R ligands.•Compound 8d showed high affinity for H3R, low affinities for ten other off-target receptors, and negligible effects on hERG.•Compound 8d exerted dose-dependent antinociceptive effects in the formalin-induced pain and chronic constriction injury (CCI) models.•Compound 8d exhibited an excellent safety profile in acute toxicity test and had a favorable drug-like pharmacokinetic profile.