FLUORINATED QUINOLINE, QUINOXALINE AND BENZOB1,4OXAZINE DERIVATIVES AS DIHYDROOROTATE DEHYDROGENASE (DHODH) INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNE AND INFLAMMATORY DISEASES

摘要

The present invention discloses compounds formula (I): (I) wherein X is CH; R2 is (AA) R3 is (BB) The present compounds of formula (I) are dihydroorotate dehydrogenase (DHODH) inhibitors, and are useful for the treatment of inflammatory disorders, autoimmune disorders and cancer, such as e.g. lymphomas, leukemias, carcinomas, and sarcomas. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 61 to 101; examples 1 to 24; tables 1 and 2). An exemplary compound is e.g. 7-(4-ethyl-3-(hydroxymethyl)-5- oxo-4,5-dihydro-1H-1,2,4-triazol-l-yl)-6-fluoro-3-(3-fluorophenyl) -1-isopropylquinolin-4(1H)-one (example 1): (CC)