Abstract
Indole-5-carboxylic acids and -carboxamides with 3-aryloxy-2-oxopropyl residues in position 1 were previously reported to be potent inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) isolated from human platelets. In continuation of our attempts to develop novel cPLA(2)alpha inhibitors, a number of derivatives of these substances characterized by bioisosteric replacement of the carboxylic acid and carboxamide functionality, respectively, were prepared. The results of the biological evaluation of the obtained compounds enabled us to gain further insight into structural features critical for cPLA(2)alpha inhibition.
MeSH terms
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Blood Platelets / drug effects
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Blood Platelets / enzymology
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Carboxylic Acids / chemical synthesis*
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Carboxylic Acids / pharmacology*
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Cytosol / drug effects
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Cytosol / enzymology
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Group IV Phospholipases A2
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Humans
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Indicators and Reagents
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Indoles / chemical synthesis*
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Indoles / pharmacology*
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Magnetic Resonance Spectroscopy
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Phospholipases A / antagonists & inhibitors*
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Propane / analogs & derivatives*
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Propane / chemical synthesis*
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Propane / pharmacology*
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Spectrometry, Mass, Electrospray Ionization
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Spectrophotometry, Ultraviolet
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Carboxylic Acids
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Enzyme Inhibitors
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Indicators and Reagents
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Indoles
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Phospholipases A
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Group IV Phospholipases A2
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Propane