Comparison of N,N'-diarylsquaramides and N,N'-diarylureas as antagonists of the CXCR2 chemokine receptor.
N,N'-diarylsquaramides were prepared and evaluated as antagonists of CXCR2. The compounds were found to be potent and selective antagonists of CXCR2. Significant differences in SAR was observed relative to the previously described N,N'-diarylurea series. As was the case in the N,N'-diarylurea series, placing sulfonamide substituent adjacent to the acidic phenol significantly reduced the clearance in rat pharmacokinetic studies.
McCleland
Brent W
BW
GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Davis
Roderick S
RS
Palovich
Michael R
MR
Widdowson
Katherine L
KL
Werner
Michelle L
ML
Burman
Miriam
M
Foley
James J
JJ
Schmidt
Dulcie B
DB
Sarau
Henry M
HM
Rogers
Martin
M
Salyers
Kevin L
KL
Gorycki
Peter D
PD
Roethke
Theresa J
TJ
Stelman
Gary J
GJ
Azzarano
Leonard M
LM
Ward
Keith W
KW
Busch-Petersen
Jakob
J
D000818:Animals; D016466:CHO Cells; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D003412:Cricetulus; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D010636:Phenols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology*
D003503:Cyclobutanes; D007202:Indicators and Reagents; D010636:Phenols; D023063:Receptors, Interleukin-8B; D013449:Sulfonamides; D014508:Urea