Discovery of potent and orally bioavailable N,N'-diarylurea antagonists for the CXCR2 chemokine receptor.

Qi Jin, Hong Nie, Brent W McCleland, Katherine L Widdowson, Michael R Palovich, John D Elliott, Richard M Goodman, Miriam Burman, Henry M Sarau, Keith W Ward, Melanie Nord, Bonnie M Orr, Peter D Gorycki, Jakob Busch-Petersen

Index: Bioorg. Med. Chem. Lett. 14(17) , 4375-8, (2004)

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Abstract

A series of 3-substituted N,N'-diarylureas was prepared and the structure-activity relationship relative to CXCR2 receptor affinity as well as their pharmacokinetic properties were examined. In vitro microsomal metabolism studies indicated that the lower clearance rates of the 3-sulfonamido-substituted compounds were most likely due to the suppression of glucuronidation.