Development of N-4,6-pyrimidine-N-alkyl-N'-phenyl ureas as orally active inhibitors of lymphocyte specific tyrosine kinase.
A new class of lymphocyte specific tyrosine kinase (lck) inhibitors based on an N-4,6-pyrimidine-N-alkyl-N'-phenyl urea scaffold is described. Many of these compounds showed low-nanomolar inhibition of lck kinase activity as well as IL-2 synthesis from Jurkat cells. One of these analogs, 7i, was shown to be orally efficacious by in vivo testing in a rat adjuvant-induced arthritis study.
Maier
Jennifer A
JA
Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd. Mason, OH 45040, USA.
Brugel
Todd A
TA
Sabat
Mark
M
Golebiowski
Adam
A
Laufersweiler
Matthew J
MJ
VanRens
John C
JC
Hopkins
Corey R
CR
De
Biswanath
B
Hsieh
Lily C
LC
Brown
Kimberly K
KK
Easwaran
Vijayasurian
V
Janusz
Michael J
MJ