Preparation of pyrazolyl urea derivatives as TrkA kinase inhibitors useful in the treatment of cancer.

Abstract

Title compds. I [R1-2 = H, alkyl, halo; A = Ph, pyridine, pyrimidine; B = phenylene, naphthylene; L = O, S, CH2; M = Ph, pyridine, pyrimidine; n = 0-1; X = O, SO2, etc.; Y = alkoxy, oxycarbonyl, amino, etc.] are prepd. For instance, II is prepd. from 4-[3-tert-butyl-5-[N'-[4-(pyridin-4-yloxy)phenyl]ureido]pyrazol-1-yl]benzoic acid Me ester (prepn. given) and 2-(pyrrolidin-1-yl)ethylamine (DCE, AlMe3, 80°, 16 h). Compds. of the invention show significant inhibition of TrkA kinase (IC50 < 1 μM). I are useful for the treatment of cancer. [on SciFinder(R)]