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)

Bertrand Le Bourdonnec; 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

doi:10.1021/jm8008986

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)

Bertrand Le Bourdonnec
, 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

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

Abstract

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

Original language	English
Pages (from-to)	5893-5896
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	19
DOIs	https://doi.org/10.1021/jm8008986
State	Published - Oct 9 2008

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Le Bourdonnec, B., Windh, R. T., Ajello, C. W., Leister, L. K., Gu, M., Chu, G. H., Tuthill, P. A., Barker, W. M., Koblish, M., Wiant, D. D., Graczyk, T. M., Belanger, S., Cassel, J. A., Feschenko, M. S., Brogdon, B. L., Smith, S. A., Christ, D. D., Derelanko, M. J., Kutz, S., ... Dolle, R. E. (2008). 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). Journal of Medicinal Chemistry, 51(19), 5893-5896. https://doi.org/10.1021/jm8008986

@article{429cadbd05364a8d97a9628436250f9b,

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 δ 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 δ agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.",

author = "\{Le Bourdonnec\}, Bertrand and Windh, \{Rolf T.\} and Ajello, \{Christopher W.\} and Leister, \{Lara K.\} and Minghua Gu and Chu, \{Guo Hua\} and Tuthill, \{Paul A.\} and Barker, \{William M.\} and Michael Koblish and Wiant, \{Daniel D.\} and Graczyk, \{Thomas M.\} and Serge Belanger and Cassel, \{Joel A.\} and Feschenko, \{Marina S.\} and Brogdon, \{Bernice L.\} and Smith, \{Steven A.\} and Christ, \{David D.\} and Derelanko, \{Michael J.\} and Steve Kutz and Little, \{Patrick J.\} and DeHaven, \{Robert N.\} and DeHaven-Hudkins, \{Diane L.\} and Dolle, \{Roland E.\}",

year = "2008",

month = oct,

day = "9",

doi = "10.1021/jm8008986",

language = "English",

volume = "51",

pages = "5893--5896",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

number = "19",

}

Le Bourdonnec, B, Windh, RT, Ajello, CW, Leister, LK, Gu, M, Chu, GH, Tuthill, PA, Barker, WM, Koblish, M, Wiant, DD, Graczyk, TM, Belanger, S, Cassel, JA, Feschenko, MS, Brogdon, BL, Smith, SA, Christ, DD, Derelanko, MJ, Kutz, S, Little, PJ, DeHaven, RN, DeHaven-Hudkins, DL & Dolle, RE 2008, '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)', Journal of Medicinal Chemistry, vol. 51, no. 19, pp. 5893-5896. https://doi.org/10.1021/jm8008986

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). / Le Bourdonnec, Bertrand; Windh, Rolf T.; Ajello, Christopher W. et al.
In: Journal of Medicinal Chemistry, Vol. 51, No. 19, 09.10.2008, p. 5893-5896.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain

T2 - Discovery of N,N-diethyl-4-(5-hydroxyspiro-[chromene-2, 4′-piperidine]-4-yl)benzamide (ADL5859)

AU - Le Bourdonnec, Bertrand

AU - Windh, Rolf T.

AU - Ajello, Christopher W.

AU - Leister, Lara K.

AU - Gu, Minghua

AU - Chu, Guo Hua

AU - Tuthill, Paul A.

AU - Barker, William M.

AU - Koblish, Michael

AU - Wiant, Daniel D.

AU - Graczyk, Thomas M.

AU - Belanger, Serge

AU - Cassel, Joel A.

AU - Feschenko, Marina S.

AU - Brogdon, Bernice L.

AU - Smith, Steven A.

AU - Christ, David D.

AU - Derelanko, Michael J.

AU - Kutz, Steve

AU - Little, Patrick J.

AU - DeHaven, Robert N.

AU - DeHaven-Hudkins, Diane L.

AU - Dolle, Roland E.

PY - 2008/10/9

Y1 - 2008/10/9

N2 - Selective δ 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 δ agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.

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

UR - https://www.scopus.com/pages/publications/53549092761

U2 - 10.1021/jm8008986

DO - 10.1021/jm8008986

M3 - Article

C2 - 18788723

AN - SCOPUS:53549092761

SN - 0022-2623

VL - 51

SP - 5893

EP - 5896

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 19

ER -

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)

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