Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3.
A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been synthesized and their affinity for the receptor evaluated. Compounds were evaluated in a (125)I-IP10 displacement assay and in in vitro cell migration assays to IP10, ITAC, and MIG using human peripheral blood mononuclear cells.
Johnson
Michael
M
Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
Li
An-Rong
AR
Liu
Jiwen
J
Fu
Zice
Z
Zhu
Liusheng
L
Miao
Shichang
S
Wang
Xuemei
X
Xu
Qingge
Q
Huang
Alan
A
Marcus
Andrew
A
Xu
Feng
F
Ebsworth
Karen
K
Sablan
Emmanuel
E
Danao
Jay
J
Kumer
Jeff
J
Dairaghi
Dan
D
Lawrence
Chris
C
Sullivan
Tim
T
Tonn
George
G
Schall
Thomas
T
Collins
Tassie
T
Medina
Julio
J
D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007457:Iodine Radioisotopes; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D009842:Oligopeptides / Q000378:metabolism; D052999:Quinazolinones / Q000138:chemical synthesis / Q000494:pharmacology*; D011869:Radioligand Assay; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D018121:Receptors, Cytokine / Q000378:metabolism; D013329:Structure-Activity Relationship
C515187:CXCR3 protein, human; C515188:Cxcr3 protein, mouse; C104577:IP10-Mig receptor; C519300:ITAC peptide; D036341:Intercellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D052999:Quinazolinones; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine