Development of N-4, 6-pyrimidine-N-alkyl-N′-phenyl ureas as orally active inhibitors of lymphocyte specific tyrosine kinase

…, A Golebiowski, MJ Laufersweiler, JC VanRens…

Index: Maier, Jennifer A.; Brugel, Todd A.; Sabat, Mark; Golebiowski, Adam; Laufersweiler, Matthew J.; VanRens, John C.; Hopkins, Corey R.; De, Biswanath; Hsieh, Lily C.; Brown, Kimberly K.; Easwaran, Vijayasurian; Janusz, Michael J. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 14 p. 3646 - 3650

Full Text: HTML

Citation Number: 19

Abstract

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.