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)

J Med Chem. 2008 Oct 9;51(19):5893-6. doi: 10.1021/jm8008986. Epub 2008 Sep 13.

Abstract

Selective delta 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 delta agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Analgesics / administration & dosage*
  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Animals
  • Benzamides / administration & dosage*
  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzopyrans / administration & dosage*
  • Benzopyrans / chemical synthesis
  • Benzopyrans / chemistry
  • Biological Availability
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug-Related Side Effects and Adverse Reactions
  • Ether-A-Go-Go Potassium Channels / drug effects
  • Humans
  • Maximum Tolerated Dose
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects
  • Pain / drug therapy*
  • Pain Measurement / drug effects
  • Rats
  • Receptors, Opioid, delta / agonists*
  • Toxicity Tests

Substances

  • Analgesics
  • Benzamides
  • Benzopyrans
  • Ether-A-Go-Go Potassium Channels
  • N,N-diethyl-4-(5-hydroxyspiro(chromene-2,4'-piperidine)-4-yl)benzamide
  • Receptors, Opioid, delta