Bioorganic & Medicinal Chemistry Letters 2008-03-15

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

Michael P Winters, Carl Crysler, Nalin Subasinghe, Declan Ryan, Lynette Leong, Shuyuan Zhao, Robert Donatelli, Edward Yurkow, Marie Mazzulla, Lisa Boczon, Carl L Manthey, Christopher Molloy, Holly Raymond, Lynne Murray, Laura McAlonan, Bruce Tomczuk

Index: Bioorg. Med. Chem. Lett. 18(6) , 1926-30, (2008)

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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.


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