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.
Bertrand Le Bourdonnec  1 ,  Rolf T Windh ,  Christopher W Ajello ,  Lara K Leister ,  Minghua Gu ,  Guo-Hua Chu ,  Paul A Tuthill ,  William M Barker ,  Michael Koblish ,  Daniel D Wiant ,  Thomas M Graczyk ,  Serge Belanger ,  Joel A Cassel ,  Marina S Feschenko ,  Bernice L Brogdon ,  Steven A Smith ,  David D Christ ,  Michael J Derelanko ,  Steve Kutz ,  Patrick J Little ,  Robert N DeHaven ,  Diane L DeHaven-Hudkins ,  Roland E Dolle
Affiliations
  • 1. Department of Chemistry, Adolor Corporation, Exton, Pennsylvania 19341, USA. [email protected]
PMID: 18788723 DOI: 10.1021/jm8008986
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.

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