title: 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).
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.
authors.affiliation: Department of Chemistry, Adolor Corporation, Exton, Pennsylvania 19341, USA. blebourdonnec@adolor.com
authors.forename: Bertrand
authors.initials: B
authors.lastname: Le Bourdonnec
authors.forename: Rolf T
authors.initials: RT
authors.lastname: Windh
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ajello
authors.forename: Lara K
authors.initials: LK
authors.lastname: Leister
authors.forename: Minghua
authors.initials: M
authors.lastname: Gu
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Chu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tuthill
authors.forename: William M
authors.initials: WM
authors.lastname: Barker
authors.forename: Michael
authors.initials: M
authors.lastname: Koblish
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Wiant
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Graczyk
authors.forename: Serge
authors.initials: S
authors.lastname: Belanger
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cassel
authors.forename: Marina S
authors.initials: MS
authors.lastname: Feschenko
authors.forename: Bernice L
authors.initials: BL
authors.lastname: Brogdon
authors.forename: Steven A
authors.initials: SA
authors.lastname: Smith
authors.forename: David D
authors.initials: DD
authors.lastname: Christ
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Derelanko
authors.forename: Steve
authors.initials: S
authors.lastname: Kutz
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Little
authors.forename: Robert N
authors.initials: RN
authors.lastname: DeHaven
authors.forename: Diane L
authors.initials: DL
authors.lastname: DeHaven-Hudkins
authors.forename: Roland E
authors.initials: RE
authors.lastname: Dolle
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D001578:Benzopyrans / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D001682:Biological Availability; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D006801:Humans; D020714:Maximum Tolerated Dose; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists*; D018675:Toxicity Tests
chemical_list: D000700:Analgesics; D001549:Benzamides; D001578:Benzopyrans; D051638:Ether-A-Go-Go Potassium Channels; C532570:N,N-diethyl-4-(5-hydroxyspiro(chromene-2,4'-piperidine)-4-yl)benzamide; D017465:Receptors, Opioid, delta