Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors.
A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.
Das
Jagabandhu
J
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. jagabandhu.das@bms.com
Furch
Joseph A
JA
Liu
Chunjian
C
Moquin
Robert V
RV
Lin
James
J
Spergel
Steven H
SH
McIntyre
Kim W
KW
Shuster
David J
DJ
O'Day
Kathleen D
KD
Penhallow
Becky
B
Hung
Chen-Yi
CY
Doweyko
Arthur M
AM
Kamath
Amrita
A
Zhang
Hongjian
H
Marathe
Punit
P
Kanner
Steven B
SB
Lin
Tai-An
TA
Dodd
John H
JH
Barrish
Joel C
JC
Wityak
John
J