Discovery of polar spirocyclic orally bioavailable urea inhibitors of soluble epoxide hydrolase.

•Inhibition of soluble epoxide hydrolase can offer therapy for in many diseases.•A novel spirocyclic diamine scaffold was explored in the design of sEH inhibitors.•Low nanomolar lead inhibitor was identified which is chiral and non-racemic.•The lead compound is distinctly polar, water-soluble and orally bioavailable.•Crystal structure of the lead inhibitor with sEH was obtained.