2-((5-(PHENYL)-PYRROLO2,1-F1,2,4TRIAZIN-4-YL)AMINO)-3-(PHENYL)PROPANOIC ACID DERIVATIVES AND RELATED COMPOUNDS AS MCL-1 ENZYME INHIBITORS FOR TREATING CANCER

摘要

A compound of formula I (the variables are defined in the claims) or a pharmaceutically acceptable salt or solvate thereof, as an MCL-1 enzyme inhibitor for treating colon cancer, breast cancer, small-cell lung cancer, non-small- cell lung cancer, bladder cancer, ovarian cancer, prostate cancer, chronic lymphoid leukemia, lymphoma, myeloma, acute myeloid leukemia, or pancreatic cancer. The present description discloses the synthesis of exemplary compounds as well as biological assays thereof (e.g. pages 55 to 114; paragraphs [00216] to [00304]; examples 1 to 33; tables A and 2). An exemplary compound is e.g. (2R)-2-{[(5Ra)-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-l-yl) ethoxy]phenyl}-6-(4-fluorophenyl) py rrolo[2, l-f][l, 2, 4]triazin-4-yl]am ino}-3-(2-{[2-(2-methoxy phenyl) py rim idin-4-yl]methoxy} phenyl) propanoic acid (example 13) with e.g. 0.7 nM BIM_Ki in an cell free MCL-1 Bim affinity assay.