Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB 2 receptor agonists for pain management

Derek W. Nelson; Jennifer M. Frost; Karin R. Tietje; Alan S. Florjancic; Keith Ryther; William A. Carroll; Michael J. Dart; Anthony V. Daza; Bradley A. Hooker; George K. Grayson; Yihong Fan; Tiffany R. Garrison; Odile F. El-Kouhen; Betty Yao; Madhavi Pai; Prasant Chandran; Chang Zhu; Gin C. Hsieh; Michael D. Meyer

doi:10.1016/j.bmcl.2012.01.121

Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB ₂ receptor agonists for pain management

Derek W. Nelson^*, Jennifer M. Frost, Karin R. Tietje, Alan S. Florjancic, Keith Ryther, William A. Carroll, Michael J. Dart, Anthony V. Daza, Bradley A. Hooker, George K. Grayson, Yihong Fan, Tiffany R. Garrison, Odile F. El-Kouhen, Betty Yao, Madhavi Pai, Prasant Chandran, Chang Zhu, Gin C. Hsieh, Michael D. Meyer

^*Corresponding author for this work

Chemistry

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

15 Scopus citations

Abstract

SAR studies on a series of thiophene amide derivatives provided CB ₂ receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB ₂ over CB ₁ effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB ₂ antagonist demonstrated the efficacy in the pain models resulted from CB ₂ agonism.

Original language	English (US)
Pages (from-to)	2604-2608
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2012.01.121
State	Published - Apr 1 2012

Keywords

CB2 agonists
Pain management

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmaceutical Science
Organic Chemistry

Access to Document

10.1016/j.bmcl.2012.01.121

Cite this

Nelson, D. W., Frost, J. M., Tietje, K. R., Florjancic, A. S., Ryther, K., Carroll, W. A., Dart, M. J., Daza, A. V., Hooker, B. A., Grayson, G. K., Fan, Y., Garrison, T. R., El-Kouhen, O. F., Yao, B., Pai, M., Chandran, P., Zhu, C., Hsieh, G. C., & Meyer, M. D. (2012). Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB ₂ receptor agonists for pain management. Bioorganic and Medicinal Chemistry Letters, 22(7), 2604-2608. https://doi.org/10.1016/j.bmcl.2012.01.121

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abstract = "SAR studies on a series of thiophene amide derivatives provided CB 2 receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB 2 over CB 1 effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB 2 antagonist demonstrated the efficacy in the pain models resulted from CB 2 agonism.",

keywords = "CB2 agonists, Pain management",

author = "Nelson, {Derek W.} and Frost, {Jennifer M.} and Tietje, {Karin R.} and Florjancic, {Alan S.} and Keith Ryther and Carroll, {William A.} and Dart, {Michael J.} and Daza, {Anthony V.} and Hooker, {Bradley A.} and Grayson, {George K.} and Yihong Fan and Garrison, {Tiffany R.} and El-Kouhen, {Odile F.} and Betty Yao and Madhavi Pai and Prasant Chandran and Chang Zhu and Hsieh, {Gin C.} and Meyer, {Michael D.}",

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Nelson, DW, Frost, JM, Tietje, KR, Florjancic, AS, Ryther, K, Carroll, WA, Dart, MJ, Daza, AV, Hooker, BA, Grayson, GK, Fan, Y, Garrison, TR, El-Kouhen, OF, Yao, B, Pai, M, Chandran, P, Zhu, C, Hsieh, GC & Meyer, MD 2012, 'Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB ₂ receptor agonists for pain management', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 7, pp. 2604-2608. https://doi.org/10.1016/j.bmcl.2012.01.121

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AU - Frost, Jennifer M.

AU - Tietje, Karin R.

AU - Florjancic, Alan S.

AU - Ryther, Keith

AU - Carroll, William A.

AU - Dart, Michael J.

AU - Daza, Anthony V.

AU - Hooker, Bradley A.

AU - Grayson, George K.

AU - Fan, Yihong

AU - Garrison, Tiffany R.

AU - El-Kouhen, Odile F.

AU - Yao, Betty

AU - Pai, Madhavi

AU - Chandran, Prasant

AU - Zhu, Chang

AU - Hsieh, Gin C.

AU - Meyer, Michael D.

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