Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists

Karin Worm; Damian G. Weaver; Rosalyn C. Green; Christopher T. Saeui; Doreen Marie S. Dulay; William M. Barker; Joel A. Cassel; Gabriel J. Stabley; Robert N. DeHaven; Christopher J. LaBuda; Michael Koblish; Bernice L. Brogdon; Steven A. Smith; Roland E. Dolle

doi:10.1016/j.bmcl.2009.07.057

Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB₂ agonists

Karin Worm
, Damian G. Weaver
, Rosalyn C. Green
, Christopher T. Saeui
, Doreen Marie S. Dulay
, William M. Barker
, Joel A. Cassel
, Gabriel J. Stabley
, Robert N. DeHaven
, Christopher J. LaBuda
, Michael Koblish
, Bernice L. Brogdon
, Steven A. Smith
, Roland E. Dolle

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

11 Scopus citations

Abstract

Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB₂ agonists. Selective CB₂ agonist 31 (K_i = 2.7; CB₁/CB₂ = 190) displayed robust activity in a rodent model of postoperative pain.

Original language	English
Pages (from-to)	5004-5008
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2009.07.057
State	Published - Sep 1 2009

Keywords

Antiallodynic activity
Cannabinoid CB receptor agonist
Metabolic stability
Selectivity
Structure-activity relationship

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10.1016/j.bmcl.2009.07.057

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Worm, K., Weaver, D. G., Green, R. C., Saeui, C. T., Dulay, D. M. S., Barker, W. M., Cassel, J. A., Stabley, G. J., DeHaven, R. N., LaBuda, C. J., Koblish, M., Brogdon, B. L., Smith, S. A., & Dolle, R. E. (2009). Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB₂ agonists. Bioorganic and Medicinal Chemistry Letters, 19(17), 5004-5008. https://doi.org/10.1016/j.bmcl.2009.07.057

@article{1165f064ea2e4da381aa19bb07cbaa0e,

title = "Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists",

abstract = "Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists. Selective CB2 agonist 31 (Ki = 2.7; CB1/CB2 = 190) displayed robust activity in a rodent model of postoperative pain.",

keywords = "Antiallodynic activity, Cannabinoid CB receptor agonist, Metabolic stability, Selectivity, Structure-activity relationship",

author = "Karin Worm and Weaver, \{Damian G.\} and Green, \{Rosalyn C.\} and Saeui, \{Christopher T.\} and Dulay, \{Doreen Marie S.\} and Barker, \{William M.\} and Cassel, \{Joel A.\} and Stabley, \{Gabriel J.\} and DeHaven, \{Robert N.\} and LaBuda, \{Christopher J.\} and Michael Koblish and Brogdon, \{Bernice L.\} and Smith, \{Steven A.\} and Dolle, \{Roland E.\}",

year = "2009",

month = sep,

day = "1",

doi = "10.1016/j.bmcl.2009.07.057",

language = "English",

volume = "19",

pages = "5004--5008",

journal = "Bioorganic and Medicinal Chemistry Letters",

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}

Worm, K, Weaver, DG, Green, RC, Saeui, CT, Dulay, DMS, Barker, WM, Cassel, JA, Stabley, GJ, DeHaven, RN, LaBuda, CJ, Koblish, M, Brogdon, BL, Smith, SA & Dolle, RE 2009, 'Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB₂ agonists', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 17, pp. 5004-5008. https://doi.org/10.1016/j.bmcl.2009.07.057

TY - JOUR

T1 - Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists

AU - Worm, Karin

AU - Weaver, Damian G.

AU - Green, Rosalyn C.

AU - Saeui, Christopher T.

AU - Dulay, Doreen Marie S.

AU - Barker, William M.

AU - Cassel, Joel A.

AU - Stabley, Gabriel J.

AU - DeHaven, Robert N.

AU - LaBuda, Christopher J.

AU - Koblish, Michael

AU - Brogdon, Bernice L.

AU - Smith, Steven A.

AU - Dolle, Roland E.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists. Selective CB2 agonist 31 (Ki = 2.7; CB1/CB2 = 190) displayed robust activity in a rodent model of postoperative pain.

AB - Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists. Selective CB2 agonist 31 (Ki = 2.7; CB1/CB2 = 190) displayed robust activity in a rodent model of postoperative pain.

KW - Antiallodynic activity

KW - Cannabinoid CB receptor agonist

KW - Metabolic stability

KW - Selectivity

KW - Structure-activity relationship

UR - https://www.scopus.com/pages/publications/68349133322

U2 - 10.1016/j.bmcl.2009.07.057

DO - 10.1016/j.bmcl.2009.07.057

M3 - Article

C2 - 19646869

AN - SCOPUS:68349133322

SN - 0960-894X

VL - 19

SP - 5004

EP - 5008

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 17

ER -

Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB₂ agonists

Abstract

Keywords

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