Disubstituted pyrimidines as Lck inhibitors.
We have developed a family of 4-benzimidazolyl-N-piperazinethyl-pyrimidin-2-amines that are subnanomolar inhibitors of Lck. A subset of these Lck inhibitors, with heterocyclic substituents at the benzimidazole C5, are also low-nanomolar inhibitors of cellular IL2 release.
Hunt
Julianne A
JA
Merck Research Laboratories, Merck & Co., PO Box 2000, Rahway, NJ 07065, United States. julianne_hunt@merck.com
Beresis
Richard T
RT
Goulet
Joung L
JL
Holmes
Mark A
MA
Hong
Xinfang J
XJ
Kovacs
Ernest
E
Mills
Sander G
SG
Ruzek
Rowena D
RD
Wong
Frederick
F
Hermes
Jeffrey D
JD
Park
Young-Whan
YW
Salowe
Scott P
SP
Sonatore
Lisa M
LM
Wu
Lin
L
Woods
Andrea
A
Zaller
Dennis M
DM
Sinclair
Peter J
PJ
D020128:Inhibitory Concentration 50; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)