2-pyrazole anilines and related analogs for inhibiting YAP/TAZ-TEAD
The present disclosure relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of YAP/TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds.
1 . A compound selected from 1-(3-(6-(4-fluorophenyl)-4-(1-methyl-1H-pyrazol-3-yl) pyridazin-3-yl) pyrrolidin-1-yl) prop-2-en-1-one and pharmaceutically acceptable salts thereof.
2 . The compound of claim 1 , wherein the compound is (R)-1-(3-(6-(4-fluorophenyl)-4-(1-methyl-1H-pyrazol-3-yl) pyridazin-3-yl) pyrrolidin-1-yl) prop-2-en-1-one or a pharmaceutically acceptable salt thereof.
3 . The compound of claim 1 , wherein the compound is (S)-1-(3-(6-(4-fluorophenyl)-4-(1-methyl-1H-pyrazol-3-yl) pyridazin-3-yl) pyrrolidin-1-yl) prop-2-en-1-one or a pharmaceutically acceptable salt thereof.
4 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
5 . A method of treating a YAP/TAZ-TEAD activation mediated disorder in a patient in need thereof comprising administering to the patient an effective amount of a compound of claim 1 .
6 . The method of claim 5 , further comprising administering to the patient one or more additional active agents selected from the group consisting of EGFR inhibitors, MEK inhibitors, AXL inhibitors, B-RAF inhibitors, RAS inhibitors, and any combination of any of the foregoing.
7 . A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
8 . A method of treating a YAP/TAZ-TEAD activation mediated disorder in a patient in need thereof comprising administering to the patient an effective amount of a compound of claim 2 .
9 . The method of claim 8 , further comprising administering to the patient one or more additional active agents selected from the group consisting of EGFR inhibitors, MEK inhibitors, AXL inhibitors, B-RAF inhibitors, RAS inhibitors, and any combination of any of the foregoing.
10 . A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier.
11 . A method of treating a YAP/TAZ-TEAD activation mediated disorder in a patient in need thereof comprising administering to the patient an effective amount of a compound of claim 3 .
12 . The method of claim 11 , further comprising administering to the patient one or more additional active agents selected from the group consisting of EGFR inhibitors, MEK inhibitors, AXL inhibitors, B-RAF inhibitors, RAS inhibitors, and any combination of any of the foregoing.