TEAD inhibitors
AssigneeOrion Corporation
InventorsMarko Ahlmark, David Din Belle, Dimitris Noutsias, Pekka Pietikäinen, Petteri Rummakko, Julius Sipilä, Gerd Wohlfahrt
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Abstract
The present invention relates to a compound of formula (I) wherein A, Z, L, R1, R2, R3, R4, R5 and R33 are as defined in claim 1, or a pharmaceutically acceptable salt thereof. The compounds of formula (I) possess utility as inhibitors of TEAD. The compounds are useful as medicaments in the treatment of diseases or conditions wherein inhibition of TEAD is desired, such as cancer and chronic pain.
Claims47
A compound of formula (I) or a pharmaceutically acceptable salt thereof
- wherein
- A is phenyl or pyridyl;
- L is —O—;
- R1 is C1-7 alkoxy;
- R2 is hydrogen;
- R3 is hydrogen;
- R4 is halogen C1-7 alkyl;
- R5 is hydrogen;
- R33 and R42 are hydrogen;
- Z is ring (1a) or (12)
- R6 is hydrogen, C1-7 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-7 alkyl, —C(O)—RX, C1-7 alkoxy C1-7 alkyl, C1-7 alkoxycarbonyl C1-7 alkyl, —SO2C1-7 alkyl, —C1-7 alkyl-C(O)—NR23R24, or an optionally substituted 4-6 membered ring having 0-3 heteroatoms as ring atoms independently selected from O, S, and N;
- RX is C1-7 alkyl, C3-7 cycloalkyl, C1-7 alkoxy C1-7 alkyl, C1-7 alkyl-NR36R37, or an optionally substituted 4-6 membered ring having 0-3 heteroatoms as ring atoms independently selected from O, S, and N;
- R7, R8, R18, R20, R21, and R22 are, independently, hydrogen, C1-7 alkyl, C3-7 cycloalkyl, hydroxyl, C1-7 alkoxy, or C1-7 alkylcarbonyl;
- R23, R24, R36, and R37 are, independently, hydrogen or C1-7 alkyl;
- wherein optional substitution, in each occurrence, is 1-2 substituents independently selected from C1-7 alkyl, halogen, halogen C1-7 alkyl, C1-7 alkoxy, and oxo.
A method for the treatment of cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof
- wherein
- A is phenyl or pyridyl;
- L is —O—;
- R1 is C1-7 alkoxy;
- R2 is hydrogen;
- R3 is hydrogen;
- R4 is halogen C1-7 alkyl;
- R5 is hydrogen;
- R33 and R42 are hydrogen;
- Z is ring (1a) or (12)
- R6 is hydrogen, C1-7 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-7 alkyl, —C(O)—RX, C1-7 alkoxy C1-7 alkyl, C1-7 alkoxycarbonyl C1-7 alkyl, —SO2C1-7 alkyl, —C1-7 alkyl-C(O)—NR23R24 or an optionally substituted 4-6 membered ring having 0-3 heteroatoms as ring atoms independently selected from O, S, and N;
- RX is C1-7 alkyl, C3-7 cycloalkyl, C1-7 alkoxy C1-7 alkyl, C1-7 alkyl-NR36R37, or an optionally substituted 4-6 membered ring having 0-3 heteroatoms as ring atoms independently selected from O, S, and N;
- R7, R8, R18, R20, R21, and R22 are, independently, hydrogen, C1-7 alkyl, C3-7 cycloalkyl, hydroxyl, C1-7 alkoxy or C1-7 alkylcarbonyl;
- R23, R24, R36, and R37 are, independently, hydrogen, or C1-7 alkyl;
- wherein optional substitution, in each occurrence, is 1-2 substituents independently selected from C1-7 alkyl, halogen, halogen C1-7 alkyl, C1-7 alkoxy, and oxo.
Dependencies are inferred from the claim text.