Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist.
Structure-activity studies on lead cyclobutenedione 3 led to the discovery of 4 (SCH 527123), a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist with excellent cell-based activity. Compound 4 displayed good oral bioavailability in rat and may be a potential therapeutic agent for the treatment of various inflammatory diseases.
Dwyer
Michael P
MP
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. michael.dwyer@spcorp.com
Yu
Younong
Y
Chao
Jianping
J
Aki
Cynthia
C
Chao
Jianhua
J
Biju
Purakkattle
P
Girijavallabhan
Viyyoor
V
Rindgen
Diane
D
Bond
Richard
R
Mayer-Ezel
Rosemary
R
Jakway
James
J
Hipkin
R William
RW
Fossetta
James
J
Gonsiorek
Waldemar
W
Bian
Hong
H
Fan
Xuedong
X
Terminelli
Carol
C
Fine
Jay
J
Lundell
Daniel
D
Merritt
J Robert
JR
Rokosz
Laura L
LL
Kaiser
Bernd
B
Li
Ge
G
Wang
Wei
W
Stauffer
Tara
T
Ozgur
Lynne
L
Baldwin
John
J
Taveras
Arthur G
AG
D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001682:Biological Availability; D003503:Cyclobutanes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C516686:2-hydroxy-N,N-dimethyl-3-(2-((1-(5-methylfuran-2-yl)propyl)amino)-3,4-dioxocyclobut-1-enylamino)benzamide; D001549:Benzamides; D003503:Cyclobutanes; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C037689:benzamide