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US 2013/0172384 A1Published application
Fatty acid synthase inhibitors
AssigneeGlaxoSmithKline Intellectual Property Development Limited
InventorsNicholas D. Adams, Christopher Joseph Aquino, Jonathan M. Ghergurovich, David Lee Musso, Cynthia A. Parrish
Life of this patent
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Abstract
This invention relates to the use of triazolone and triazolethione derivatives for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of triazolones and triazolethiones in the treatment of cancer.
Claims14
A compound of Formula (I):
- wherein:
- R1 is phenyl, naphthyl, 5- or 6-membered heteroaryl, or 9- or 10-membered heterocyclyl;
- wherein said phenyl, naphthyl, 5- or 6-membered heteroaryl, or 9- or 10-membered heterocyclyl is optionally substituted 1 to 3 times independently by halogen, (C1-C4)alkyl, —CF3, (C3-C7)cycloalkyl, —CO(C1-C4)alkyl, —CO(C3-C7)cycloalkyl, —CO(phenyl), carboxyl, —CO2(C1-C4)alkyl, —CONR5R6, phenyl, —SO2(C1-C4)alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, (C1-C4)alkoxy, (C3-C7)cycloalkoxy, hydroxy(C1-C4)alkyl-, (C1-C4)alkoxy(C1-C4)alkyl-, —OCF3, —NR5R6, R5R6N(C1-C4)alkyl-, —NHCO(C1-C4)alkyl, —NHCONR5R6, —NHSO2(C1-C4)alkyl, —NHSO2NR5R6, or R9;
- when present each R2 is independently selected from the group consisting of halogen, (C1-C6)alkyl, hydroxyl, and (C1-C4)alkoxy;
- R3 is selected from the group consisting of (C1-C6)alkyl, —CF3, (C3-C7)cycloalkyl, (C1-C4)alkoxy, and —NR7R8;
- wherein said (C1-C6)alkyl is optionally substituted by hydroxyl, (C1-C4)alkoxy, —CF3, or cyano, and wherein said (C3-C7)cycloalkyl is optionally substituted 1 or 2 times independently by halogen, (C1-C4)alkyl, hydroxy(C1-C4)alkyl-, (C1-C4)alkoxy(C1-C4)alkyl-, —CF3, or cyano;
- R4 is hydrogen, (C1-C6)alkyl, (C3-C7)cycloalkyl, —CO(C1-C4)alkyl, —CO(C3-C7)cycloalkyl, or —CONR5R6;
- wherein said (C1-C6)alkyl is optionally substituted by —CF3, cyano, phenyl, —CONR5R6, hydroxyl, (C1-C4)alkoxy, or —NR5R6;
- R5 is selected from the group consisting of hydrogen, (C1-C4)alkyl, (C3-C7)cycloalkyl, phenyl, and phenyl(C1-C3)alkyl-;
- R6 is hydrogen, (C1-C4)alkyl, or (C3-C7)cycloalkyl;
- or R5 and R6 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which ring is optionally substituted 1 or 2 times independently by oxo or (C1-C4)alkyl;
- R7 and R8 are each independently hydrogen, (C1-C4)alkyl, or (C3-C7)cycloalkyl;
- or R7 and R8 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which ring is optionally substituted 1 or 2 times independently by oxo or (C1-C4)alkyl;
- R9 is a 5-membered heteroaryl ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, or a 6-membered heteroaryl ring containing 1 to 3 nitrogen atoms, which 5- or 6-membered ring is optionally substituted 1 or 2 times independently by halogen, (C1-C4)alkyl, —CF3, (C1-C4)alkoxy, or —NR5R6;
- X is O or S;
- m is 0-3;
- and
- n is 1 or 2;
- or pharmaceutically acceptable salts thereof.
16 more elements
A compound of Formula (I)(A):
- wherein:
- R1 is phenyl, naphthyl, 5- or 6-membered heteroaryl, or 9- or 10-membered heterocyclyl;
- wherein said phenyl, naphthyl, 5- or 6-membered heteroaryl, or 9- or 10-membered heterocyclyl is optionally substituted 1 to 3 times independently by halogen, (C1-C4)alkyl, —CF3, (C3-C7)cycloalkyl, —CO(C1-C4)alkyl, —CO(C3-C7)cycloalkyl, —CO(phenyl), carboxyl, —CO2(C1-C4)alkyl, —CONR5R6, phenyl, —SO2(C1-C4)alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, (C1-C4)alkoxy, (C3-C7)cycloalkoxy, hydroxy(C1-C4)alkyl-, (C1-C4)alkoxy(C1-C4)alkyl-, —OCF3, —NR5R6, R5R6N(C1-C4)alkyl-, —NHCO(C1-C4)alkyl, —NHCONR5R6, —NHSO2(C1-C4)alkyl, —NHSO2NR5R6, or R9;
- when present each R2 is independently selected from the group consisting of halogen, (C1-C6)alkyl, hydroxyl, and (C1-C4)alkoxy;
- R3 is selected from the group consisting of (C1-C6)alkyl, —CF3, (C3-C7)cycloalkyl, (C1-C4)alkoxy, and —NR7R8;
- wherein said (C1-C6)alkyl is optionally substituted by hydroxyl, (C1-C4)alkoxy, —CF3, or cyano, and wherein said (C3-C7)cycloalkyl is optionally substituted 1 or 2 times independently by halogen, (C1-C4)alkyl, hydroxy(C1-C4)alkyl-, (C1-C4)alkoxy(C1-C4)alkyl-, —CF3, or cyano;
- R4 is hydrogen, (C1-C6)alkyl, (C3-C7)cycloalkyl, —CO(C1-C4)alkyl, —CO(C3-C7)cycloalkyl, or —CONR5R6;
- wherein said (C1-C6)alkyl is optionally substituted by —CF3, cyano, phenyl, —CONR5R6, hydroxyl, (C1-C4)alkoxy, or —NR5R6;
- R5 is selected from the group consisting of hydrogen, (C1-C4)alkyl, (C3-C7)cycloalkyl, phenyl, and phenyl(C1-C3)alkyl-;
- R6 is hydrogen, (C1-C4)alkyl, or (C3-C7)cycloalkyl;
- or R5 and R6 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which ring is optionally substituted 1 or 2 times independently by oxo or (C1-C4)alkyl;
- R7 and R8 are each independently hydrogen, (C1-C4)alkyl, or (C3-C7)cycloalkyl;
- or R7 and R8 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which ring is optionally substituted 1 or 2 times independently by oxo or (C1-C4)alkyl;
- R9 is a 5-membered heteroaryl ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, or a 6-membered heteroaryl ring containing 1 to 3 nitrogen atoms, which 5- or 6-membered ring is optionally substituted 1 or 2 times independently by halogen, (C1-C4)alkyl, —CF3, (C1-C4)alkoxy, or —NR5R6;
- X is O or S;
- and
- m is 0-3;
- or pharmaceutically acceptable salts thereof.
15 more elements
A compound of Formula (I)(B):
- wherein:
- R1 is phenyl, naphthyl, 5- or 6-membered heteroaryl, or 9- or 10-membered heterocyclyl;
- wherein said phenyl, naphthyl, 5- or 6-membered heteroaryl, or 9- or 10-membered heterocyclyl is optionally substituted 1 to 3 times independently by halogen, (C1-C4)alkyl, —CF3, (C3-C7)cycloalkyl, —CO(C1-C4)alkyl, —CO(C3-C7)cycloalkyl, —CO(phenyl), carboxyl, —CO2(C1-C4)alkyl, —CONR5R6, phenyl, —SO2(C1-C4)alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, (C1-C4)alkoxy, (C3-C7)cycloalkoxy, hydroxy(C1-C4)alkyl-, (C1-C4)alkoxy(C1-C4)alkyl-, —OCF3, —NR5R6, R5R6N(C1-C4)alkyl-, —NHCO(C1-C4)alkyl, —NHCONR5R6, —NHSO2(C1-C4)alkyl, —NHSO2NR5R6, or R9;
- when present each R2 is independently selected from the group consisting of halogen, (C1-C6)alkyl, hydroxyl, and (C1-C4)alkoxy;
- R3 is selected from the group consisting of (C1-C6)alkyl, —CF3, (C3-C7)cycloalkyl, (C1-C4)alkoxy, and —NR7R8;
- wherein said (C1-C6)alkyl is optionally substituted by hydroxyl, (C1-C4)alkoxy, —CF3, or cyano, and wherein said (C3-C7)cycloalkyl is optionally substituted 1 or 2 times independently by halogen, (C1-C4)alkyl, hydroxy(C1-C4)alkyl-, (C1-C4)alkoxy(C1-C4)alkyl-, —CF3, or cyano;
- R4 is hydrogen, (C1-C6)alkyl, (C3-C7)cycloalkyl, —CO(C1-C4)alkyl, —CO(C3-C7)cycloalkyl, or —CONR5R6;
- wherein said (C1-C6)alkyl is optionally substituted by —CF3, cyano, phenyl, —CONR5R6, hydroxyl, (C1-C4)alkoxy, or —NR5R6;
- R5 is selected from the group consisting of hydrogen, (C1-C4)alkyl, (C3-C7)cycloalkyl, phenyl, and phenyl(C1-C3)alkyl-;
- R6 is hydrogen, (C1-C4)alkyl, or (C3-C7)cycloalkyl;
- or R5 and R6 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which ring is optionally substituted 1 or 2 times independently by oxo or (C1-C4)alkyl;
- R7 and R8 are each independently hydrogen, (C1-C4)alkyl, or (C3-C7)cycloalkyl;
- or R7 and R8 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which ring is optionally substituted 1 or 2 times independently by oxo or (C1-C4)alkyl;
- R9 is a 5-membered heteroaryl ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, or a 6-membered heteroaryl ring containing 1 to 3 nitrogen atoms, which 5- or 6-membered ring is optionally substituted 1 or 2 times independently by halogen, (C1-C4)alkyl, —CF3, (C1-C4)alkoxy, or —NR5R6;
- X is O or S;
- and
- m is 0-3;
- or pharmaceutically acceptable salts thereof.
15 more elements
Dependencies are inferred from the claim text.