Synthesis and SAR of novel imidazoquinoxaline-based Lck inhibitors: improvement of cell potency.
A series of anilino(imidazoquinoxaline) analogues bearing solubilizing side chains at the 6- and 7-positions of the fused phenyl ring has been prepared and evaluated for inhibition against Lck enzyme and of T-cell proliferation. Significant improvement of the cellular activity was achieved over the initial lead, compound 2.
Chen
Ping
P
Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. ping.chen@bms.com
Iwanowicz
Edwin J
EJ
Norris
Derek
D
Gu
Henry H
HH
Lin
James
J
Moquin
Robert V
RV
Das
Jagabandhu
J
Wityak
John
J
Spergel
Steven H
SH
de Fex
Henry
H
Pang
Suhong
S
Pitt
Sydney
S
Shen
Ding Ren
DR
Schieven
Gary L
GL
Barrish
Joel C
JC
D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011810:Quinoxalines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)