Optimization of the heterocyclic core of the quinazolinone-derived CXCR3 antagonists.
A series of six-six and six-five fused heterocyclic CXCR3 antagonists has been synthesized and their activities evaluated in an [(125)I]-IP-10 displacement assay and an ITAC mediated in vitro cell migration assay. The pharmacokinetic properties of several top compounds have also been studied. This effort led to the discovery of compounds with increased potency and improved pharmacokinetic properties that could serve as useful tools to study the role of the CXCR3 receptor in vivo.
Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
An-Rong
AR
Li
Michael G
MG
Johnson
Jiwen
J
Liu
Xiaoqi
X
Chen
Xiaohui
X
Du
Jeffrey T
JT
Mihalic
Jeffrey
J
Deignan
Darin J
DJ
Gustin
Jason
J
Duquette
Zice
Z
Fu
Liusheng
L
Zhu
Andrew P
AP
Marcus
Phillipe
P
Bergeron
Lawrence R
LR
McGee
Jay
J
Danao
Bryan
B
Lemon
Teresa
T
Carabeo
Timothy
T
Sullivan
Ji
J
Ma
Liang
L
Tang
George
G
Tonn
Tassie L
TL
Collins
Julio C
JC
Medina
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D052999:Quinazolinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
C515187:CXCR3 protein, human; D006571:Heterocyclic Compounds; D052999:Quinazolinones; D054367:Receptors, CXCR3