Structure-activity relationship studies on N′-aryl carbohydrazide P2X7 antagonists

Derek W. Nelson; Kathy Sarris; Douglas M. Kalvin; Marian T. Namovic; George Grayson; Diana L. Donnelly-Roberts; Richard Harris; Prisca Honore; Michael F. Jarvis; Connie R. Faltynek; William A. Carroll

doi:10.1021/jm701516f

Structure-activity relationship studies on N′-aryl carbohydrazide P2X₇ antagonists

Derek W. Nelson, Kathy Sarris, Douglas M. Kalvin, Marian T. Namovic, George Grayson, Diana L. Donnelly-Roberts, Richard Harris, Prisca Honore, Michael F. Jarvis, Connie R. Faltynek, William A. Carroll

Chemistry

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

33 Scopus citations

Abstract

N′-Aryl acyl hydrazides were identified as P2X₇ receptor antagonists. Structure-activity relationship (SAR) studies evaluated functional activity by monitoring calcium flux inhibition in cell lines expressing recombinant human and rat P2X₇ receptors. Selected analogs were assayed in vitro for their capacity to inhibit release of cytokine IL-1β. Compounds with potent antagonist function were evaluated in vivo using the zymosan-induced peritonitis model. A representative compound effectively attenuated mechanical allodynia in a rat model of neuropathic pain.

Original language	English (US)
Pages (from-to)	3030-3034
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	10
DOIs	https://doi.org/10.1021/jm701516f
State	Published - May 22 2008

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Structure-activity relationship studies on N′-aryl carbohydrazide P2X7 antagonists",

abstract = "N′-Aryl acyl hydrazides were identified as P2X7 receptor antagonists. Structure-activity relationship (SAR) studies evaluated functional activity by monitoring calcium flux inhibition in cell lines expressing recombinant human and rat P2X7 receptors. Selected analogs were assayed in vitro for their capacity to inhibit release of cytokine IL-1β. Compounds with potent antagonist function were evaluated in vivo using the zymosan-induced peritonitis model. A representative compound effectively attenuated mechanical allodynia in a rat model of neuropathic pain.",

author = "Nelson, {Derek W.} and Kathy Sarris and Kalvin, {Douglas M.} and Namovic, {Marian T.} and George Grayson and Donnelly-Roberts, {Diana L.} and Richard Harris and Prisca Honore and Jarvis, {Michael F.} and Faltynek, {Connie R.} and Carroll, {William A.}",

year = "2008",

month = may,

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doi = "10.1021/jm701516f",

language = "English (US)",

volume = "51",

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journal = "Journal of Medicinal Chemistry",

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T1 - Structure-activity relationship studies on N′-aryl carbohydrazide P2X7 antagonists

AU - Nelson, Derek W.

AU - Sarris, Kathy

AU - Kalvin, Douglas M.

AU - Namovic, Marian T.

AU - Grayson, George

AU - Donnelly-Roberts, Diana L.

AU - Harris, Richard

AU - Honore, Prisca

AU - Jarvis, Michael F.

AU - Faltynek, Connie R.

AU - Carroll, William A.

PY - 2008/5/22

Y1 - 2008/5/22

N2 - N′-Aryl acyl hydrazides were identified as P2X7 receptor antagonists. Structure-activity relationship (SAR) studies evaluated functional activity by monitoring calcium flux inhibition in cell lines expressing recombinant human and rat P2X7 receptors. Selected analogs were assayed in vitro for their capacity to inhibit release of cytokine IL-1β. Compounds with potent antagonist function were evaluated in vivo using the zymosan-induced peritonitis model. A representative compound effectively attenuated mechanical allodynia in a rat model of neuropathic pain.

AB - N′-Aryl acyl hydrazides were identified as P2X7 receptor antagonists. Structure-activity relationship (SAR) studies evaluated functional activity by monitoring calcium flux inhibition in cell lines expressing recombinant human and rat P2X7 receptors. Selected analogs were assayed in vitro for their capacity to inhibit release of cytokine IL-1β. Compounds with potent antagonist function were evaluated in vivo using the zymosan-induced peritonitis model. A representative compound effectively attenuated mechanical allodynia in a rat model of neuropathic pain.

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JO - Journal of Medicinal Chemistry

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Structure-activity relationship studies on N′-aryl carbohydrazide P2X₇ antagonists

Abstract

ASJC Scopus subject areas

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