Carboxylic acid bioisosteres acylsulfonamides, acylsulfamides, and sulfonylureas as novel antagonists of the CXCR2 receptor

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.

Graphical abstractA series of novel acylsulfamide 1, acylsulfonamide 2, and sulfonylurea 3 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.Figure optionsDownload full-size imageDownload as PowerPoint slide