Abstract
A series of novel acylsulfonamide, acylsulfamide, and sulfonylurea bioisosteres of carboxylic acids were prepared as CXCR2 antagonists. Structure-activity relationships are reported for these series. One potent orally bioavailable inhibitor had excellent PK properties and was active in a lung injury model in hyperoxia-exposed newborn rats.
MeSH terms
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Administration, Oral
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Animals
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Animals, Newborn
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Biological Availability
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Bronchoalveolar Lavage
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Carboxylic Acids / chemistry*
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Carboxylic Acids / pharmacokinetics
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Carboxylic Acids / pharmacology*
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Chemotaxis / drug effects
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Cytochrome P-450 Enzyme System / metabolism
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Humans
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Hyperoxia
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Lung / drug effects*
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Lung / metabolism
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Lung Injury
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Molecular Structure
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Neutrophils / metabolism
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Rabbits
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Rats
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Receptors, Interleukin-8B / antagonists & inhibitors*
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Structure-Activity Relationship
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Sulfonamides / chemistry*
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Sulfonic Acids / chemistry*
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Sulfonylurea Compounds / chemistry*
Substances
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Carboxylic Acids
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Receptors, Interleukin-8B
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Sulfonamides
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Sulfonic Acids
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Sulfonylurea Compounds
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Cytochrome P-450 Enzyme System
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sulfamic acid