Abstract
A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d]pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2.
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / toxicity
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Binding Sites
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Catalytic Domain
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Celecoxib
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Cell Line
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Computer Simulation
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Crystallography, X-Ray
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Cyclooxygenase 1 / chemistry
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / chemistry
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / toxicity
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Humans
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Models, Molecular
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry*
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Pyrazoles / toxicity
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Sulfonamides / chemistry
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Sulfonamides / toxicity
Substances
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2-methylbenzylamino 2-oxo-N-(4-cyano-1-phenyl-1H-pyrazol-5-yl)acetamide
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Anti-Inflammatory Agents
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Cyclooxygenase 2 Inhibitors
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N1,N2-bis(4-cyano-1-phenyl-1H-pyrazol-5-yl)oxalamide
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Pyrazoles
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Sulfonamides
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Cyclooxygenase 1
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Cyclooxygenase 2
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Celecoxib