Pyrazole compounds that modulate the activity of CDK, GSK and aurora kinases

摘要

Disclosed are benzimidazole derivatives as represented by the general formula (III) and pharmaceutical salts thereof (particularly the acetate, mesylate, ethanesulphonate, DL-Iactate, adipate, D-glucuronate, D-gluconate and hydrochloride salts); wherein E is a bond; R2 is H; R1 is a cycloalkyl group of 3 to 6 ring members, or a group CR6R7R8; R6 and R7 are each methyl; and R8 is selected from hydrogen, and methyl. Of particular importance is the compound 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea. Also disclosed are processes for the preparation of the above compounds, as well as their crystalline forms. Further disclosed is a pharmaceutical composition or a lyophilised formulation for use in the treatment of leukemia and particularly cancers such as breast cancer, ovarian cancer, colon cancer, prostate cancer, oesophageal cancer, squamous cancer, and non-small cell lung carcinomas.