Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: Discovery of N,N-diethyl-4-(5-hydroxyspiro-[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859)

摘要

Selective 6 opioid receptor agonists are promising potential therapeutic agents for the treatment of various types of pain conditions. A spirocyclic derivative was identified as a promising hit through screening. Subsequent lead optimization identified compound 20 (ADL5859) as a potent, selective, and orally bioavailable 6 agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.