adl-5859 and Pain
adl-5859 has been researched along with Pain* in 2 studies
Other Studies
2 other study(ies) available for adl-5859 and Pain
| Article | Year |
|---|---|
Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl) benzamide (ADL5747).
Selective, nonpeptidic delta opioid receptor agonists have been the subject of great interest as potential novel analgesic agents. The discoveries of BW373U86 (1) and SNC80 (2) contributed to the rapid expansion of research in this field. However, poor drug-like properties and low therapeutic indices have prevented clinical evaluation of these agents. Doses of 1 and 2 similar to those required for analgesic activity produce convulsions in rodents and nonhuman primates. Recently, we described a novel series of potent, selective, and orally bioavailable delta opioid receptor agonists. The lead derivative, ADL5859 (4), is currently in phase II proof-of-concept studies for the management of pain. Further structure activity relationship exploration has led to the discovery of ADL5747 (36), which is approximately 50-fold more potent than 4 in an animal model of inflammatory pain. On the basis of its favorable efficacy, safety, and pharmacokinetic profile, 36 was selected as a clinical candidate for the treatment of pain. Topics: Analgesics; Animals; Benzamides; Benzopyrans; CHO Cells; Clinical Trials as Topic; Cricetinae; Cricetulus; Crystallography, X-Ray; Cytochrome P-450 CYP2D6 Inhibitors; Dogs; Dose-Response Relationship, Drug; Drug Discovery; Ether-A-Go-Go Potassium Channels; Humans; Hyperalgesia; Male; Pain; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Spiro Compounds | 2009 |
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).
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. Topics: Administration, Oral; Analgesics; Animals; Benzamides; Benzopyrans; Biological Availability; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Ether-A-Go-Go Potassium Channels; Humans; Maximum Tolerated Dose; Mice; Molecular Structure; Motor Activity; Pain; Pain Measurement; Rats; Receptors, Opioid, delta; Toxicity Tests | 2008 |