N-pyridinyl acetamide derivatives as inhibitors of the Wnt signaling pathway
AssigneeRedx Pharma PLC
InventorsInder Bhamra, Matilda Bingham, Richard Testar, Louise Sargent, Craig Donoghue
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Abstract
Disclosed are compounds useful as inhibitors of the Wnt signalling pathway. Specifically, inhibitors of Porcupine (Porcn) are contemplated by the invention. In addition, the invention contemplates processes to prepare the compounds and uses of the compounds. The compounds of the invention may therefore be used in treating conditions mediated by the Wnt signalling pathway, for example, in treating cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia; or enhancing the effectiveness of an anti-cancer treatment.
Claims16
A compound of formula (III):
- wherein
- X1 and X2 are selected from the group consisting of CR6 and N, provided that X1 and X2 are not both CR6;
- het2 is a 5 or 6 membered heterocyclic ring which may be unsubstituted or substituted, and when substituted the ring is substituted with 1, 2 or 3 groups independently selected at each occurrence from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, —ORA1, —NRA1RB1, —CN, —NO2, —NRA1C(O) RB1, —C(O)NRA1RB1, NRA1SO2RB1, —SO2NRA1RB1, —SO2RA1, —C(O)RA1, —C(O)ORA1 and C3-6 cycloalkyl;
- het3 is a 5 or 6 membered heterocyclic ring or a phenyl ring which may be unsubstituted or substituted, and when substituted the ring is substituted with 1, 2 or 3 groups independently selected at each occurrence from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, —ORA1, —NRA1RB1, —CN, —NO2, —NRA1C(O)RB1, —C(O)NRA1RB1, —NRA1SO2RB1, —SO2NRA1RB1, —SO2RA1, —C(O)RA1, —C(O)ORA1 and C3-6 cycloalkyl;
- R1 and R2 are independently selected at each occurrence from the group consisting of H, halo, C1-4 alkyl, C1-4 haloalkyl, —ORA3, —NRA3RB3 and C3-6 cycloalkyl;
- R3 is selected from the group consisting of H, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl;
- R4 is independently selected at each occurrence from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, —CN, ORA4, —NRA4RB4, —SO2RA4, C3-6 cycloalkyl and C3-6 halocycloalkyl;
- R5 and R6 are, at each occurrence, independently selected from the group consisting of H, halo, C1-4 alkyl, C1-4 haloalkyl, —ORA2, —NRA2RB2, —CN, —SO2RA2, and C3-6 cycloalkyl;
- m is 1, 2 or 3;
- n is 0, 1 or 2;
- and
- RA1, RB1, RA2, RB2, RA3, RB3, RA4 and RB4 are at each occurrence independently selected from the group consisting of H, C1-4 alkyl, and C1-4 haloalkyl.
A method of treatment of a condition mediated by the Wnt signaling pathway selected from the group consisting of cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia, wherein the method comprises administering to a patient in need thereof a therapeutic amount of a compound of formula (III):
- wherein
- X1 and X2 are selected from the group consisting of CR6 and N, provided that X1 and X2 are not both CR6;
- het2 is a 5 or 6 membered heterocyclic ring which may be unsubstituted or substituted, and when substituted the ring is substituted with 1, 2 or 3 groups independently selected at each occurrence from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, —ORA1, —NRA1RB1, —CN, —NO2, —NRA1C(O) RB1, —C(O)NRA1RB1, NRA1SO2RB1, —SO2NRA1RB1, —SO2RA1, —C(O)RA1, —C(O)ORA1 and C3-6 cycloalkyl;
- het3 is a 5 or 6 membered heterocyclic ring or a phenyl ring which may be unsubstituted or substituted, and when substituted the ring is substituted with 1, 2 or 3 groups independently selected at each occurrence from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, —ORA1, —NRA1RB1, —CN, —NO2, —NRA1C(O)RB1, —C(O)NRA1RB1, —NRA1SO2RB1, —SO2NRA1RB1, —SO2RA1, —C(O)RA1, —C(O)ORA1 and C3-6 cycloalkyl;
- R1 and R2 are independently selected at each occurrence from the group consisting of H, halo, C1-4 alkyl, C1-4 haloalkyl, —ORA3, —NRA3RB3 and C3-6 cycloalkyl;
- R3 is selected from the group consisting of H, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl;
- R4 is independently selected at each occurrence from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, —CN, ORA4, —NRA4RB4, —SO2RA4, C3-6 cycloalkyl and C3-6 halocycloalkyl;
- R5 and R6 are, at each occurrence, independently selected from the group consisting of H, halo, C1-4 alkyl, C1-4 haloalkyl, —ORA2, —NRA2RB2, —CN, —SO2RA2, and C3-6 cycloalkyl;
- m is 1, 2 or 3;
- n is 0, 1 or 2;
- and
- RA1, RB1, RA2, RB2, RA3, RB3, RA4 and RB4 are at each occurrence independently selected from the group consisting of H, C1-4 alkyl, and C1-4 haloalkyl.
Dependencies are inferred from the claim text.