Novel sulfamoyl benzamides as selective CB2 agonists with improved in vitro metabolic stability

Ian Sellitto; Bertrand Le Bourdonnec; Karin Worm; Allan Goodman; Markku A. Savolainen; Guo Hua Chu; Christopher W. Ajello; Christopher T. Saeui; Lara K. Leister; Joel A. Cassel; Robert N. DeHaven; Christopher J. LaBuda; Michael Koblish; Patrick J. Little; Bernice L. Brogdon; Steven A. Smith; Roland E. Dolle

doi:10.1016/j.bmcl.2009.10.062

Novel sulfamoyl benzamides as selective CB₂ agonists with improved in vitro metabolic stability

Ian Sellitto, Bertrand Le Bourdonnec, Karin Worm, Allan Goodman, Markku A. Savolainen, Guo Hua Chu, Christopher W. Ajello, Christopher T. Saeui, Lara K. Leister, Joel A. Cassel, Robert N. DeHaven, Christopher J. LaBuda, Michael Koblish, Patrick J. Little, Bernice L. Brogdon, Steven A. Smith, Roland E. Dolle

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

16 Scopus citations

Abstract

A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB₂ agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB₂ receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB₂ agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.

Original language	English
Pages (from-to)	387-391
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2009.10.062
State	Published - Jan 1 2010

Keywords

Agonists
Analgesics
CB

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10.1016/j.bmcl.2009.10.062

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Sellitto, I., Bourdonnec, B. L., Worm, K., Goodman, A., Savolainen, M. A., Chu, G. H., Ajello, C. W., Saeui, C. T., Leister, L. K., Cassel, J. A., DeHaven, R. N., LaBuda, C. J., Koblish, M., Little, P. J., Brogdon, B. L., Smith, S. A., & Dolle, R. E. (2010). Novel sulfamoyl benzamides as selective CB₂ agonists with improved in vitro metabolic stability. Bioorganic and Medicinal Chemistry Letters, 20(1), 387-391. https://doi.org/10.1016/j.bmcl.2009.10.062

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title = "Novel sulfamoyl benzamides as selective CB2 agonists with improved in vitro metabolic stability",

abstract = "A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB2 agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB2 receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB2 agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.",

keywords = "Agonists, Analgesics, CB",

author = "Ian Sellitto and Bourdonnec, {Bertrand Le} and Karin Worm and Allan Goodman and Savolainen, {Markku A.} and Chu, {Guo Hua} and Ajello, {Christopher W.} and Saeui, {Christopher T.} and Leister, {Lara K.} and Cassel, {Joel A.} and DeHaven, {Robert N.} and LaBuda, {Christopher J.} and Michael Koblish and Little, {Patrick J.} and Brogdon, {Bernice L.} and Smith, {Steven A.} and Dolle, {Roland E.}",

year = "2010",

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doi = "10.1016/j.bmcl.2009.10.062",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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Sellitto, I, Bourdonnec, BL, Worm, K, Goodman, A, Savolainen, MA, Chu, GH, Ajello, CW, Saeui, CT, Leister, LK, Cassel, JA, DeHaven, RN, LaBuda, CJ, Koblish, M, Little, PJ, Brogdon, BL, Smith, SA & Dolle, RE 2010, 'Novel sulfamoyl benzamides as selective CB₂ agonists with improved in vitro metabolic stability', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 1, pp. 387-391. https://doi.org/10.1016/j.bmcl.2009.10.062

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T1 - Novel sulfamoyl benzamides as selective CB2 agonists with improved in vitro metabolic stability

AU - Sellitto, Ian

AU - Bourdonnec, Bertrand Le

AU - Worm, Karin

AU - Goodman, Allan

AU - Savolainen, Markku A.

AU - Chu, Guo Hua

AU - Ajello, Christopher W.

AU - Saeui, Christopher T.

AU - Leister, Lara K.

AU - Cassel, Joel A.

AU - DeHaven, Robert N.

AU - LaBuda, Christopher J.

AU - Koblish, Michael

AU - Little, Patrick J.

AU - Brogdon, Bernice L.

AU - Smith, Steven A.

AU - Dolle, Roland E.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB2 agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB2 receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB2 agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.

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KW - Agonists

KW - Analgesics

KW - CB

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AN - SCOPUS:72049099298

SN - 0960-894X

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SP - 387

EP - 391

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 1

ER -

Novel sulfamoyl benzamides as selective CB₂ agonists with improved in vitro metabolic stability

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Keywords

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