Imidazolylpyrimidine based CXCR2 chemokine receptor antagonists.
An imidazolylpyrimidine was identified in a CXCR2 chemokine receptor antagonist screen and was optimized for potency, in vitro metabolic stability, and oral bioavailability. It was found that subtle structural modification within the series affected the oral bioavailability. Potent and orally available CXCR2 antagonists are herein reported.
Ho
Koc-Kan
KK
Pharmacopeia Drug Discovery, Inc., PO Box 5350, Princeton, NJ 08543-5350, USA. kanho@pcop.com
Auld
Douglas S
DS
Bohnstedt
Adolph C
AC
Conti
Paolo
P
Dokter
Wim
W
Erickson
Shawn
S
Feng
Daming
D
Inglese
Jim
J
Kingsbury
Celia
C
Kultgen
Steven G
SG
Liu
Rong-Qiang
RQ
Masterson
Christopher M
CM
Ohlmeyer
Michael
M
Rong
Yajing
Y
Rooseboom
Martijn
M
Roughton
Andrew
A
Samama
Philippe
P
Smit
Martin-Jan
MJ
Son
Ellen
E
van der Louw
Jaap
J
Vogel
Gerard
G
Webb
Maria
M
Wijkmans
Jac
J
You
Ming
M
D000284:Administration, Oral; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D011743:Pyrimidines; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins