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

doi:10.1016/j.bmcl.2004.06.097

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

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4375-8. doi: 10.1016/j.bmcl.2004.06.097.

Authors

Qi Jin¹, 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

Affiliation

¹ GlaxoSmithKline, PO Box 1539, King of Prussia, PA 19406-0939, USA.

PMID: 15357956
DOI: 10.1016/j.bmcl.2004.06.097

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.

MeSH terms

Administration, Oral
Animals
Biological Availability
Humans
Microsomes, Liver / drug effects
Microsomes, Liver / metabolism
Protein Binding / drug effects
Protein Binding / physiology
Rats
Rats, Sprague-Dawley
Receptors, Interleukin-8B / antagonists & inhibitors*
Receptors, Interleukin-8B / metabolism
Sulfonylurea Compounds / chemistry*
Sulfonylurea Compounds / metabolism
Sulfonylurea Compounds / pharmacology

Substances

Receptors, Interleukin-8B
Sulfonylurea Compounds