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US 2019/0315756 A1Published application
Brk inhibitory compound
AssigneeOno Pharmaceutical Co., Ltd.
InventorsShingo YAMAMOTO, Hiroshi TOKURA, Masakuni KURONO, Yoshinori NOMURA, Shingo HOTTA
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Abstract
The present invention relates to a compound represented by general formula (I) (wherein, all symbols represent the same meanings as the symbols set forth in the specification), a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug of any of these. Since the compound has a Brk inhibitory activity, the compound is useful as a drug ingredient for the prevention and/or treatment of Brk-related diseases such as cancer, for example.
Claims18
A compound represented by general formula (I):
- wherein:
- represents
- Ring 1 represents a 3- to 15-membered ring;
- R1 represents a halogen, an oxo group, a hydroxyl group, a cyano group, NR4R5, a C1-4 alkyl group, or a C1-4 alkoxy group, said C1-4 alkyl group or C1-4 alkoxy group may be substituted with a halogen;
- R4 and R5 each independently represent a hydrogen atom, a C1-4 alkyl group, or a C1-4 acyl group;
- p represents an integer of 0 to 7;
- R3 represents a C1-4 alkyl group, a C2-4 alkenyl group, a C2-4 alkynyl group, a (C3-6 cycloalkyl)-(CH2)r— group, or a (3- to 6-membered saturated heterocycle)-(CH2)s— group, said R3 may be substituted with a halogen;
- r represents an integer of 0 to 4;
- s represents an integer of 0 to 4;
- Ring 2 represents a 3- to 15-membered ring;
- R2 represents a halogen, an oxo group, a hydroxyl group, a cyano group, C(O)R6, SO2R7, a C1-4 alkyl group, or a C1-4 alkoxy group,
- said C1-4 alkyl group or C1-4 alkoxy group may be substituted with a substituent selected from the group consisting of a halogen, a hydroxyl group, a cyano group, C(O)R8, NR9R10, and SO2R11;
- R6 represents a hydroxyl group, a C1-4 alkyl group, a C1-4 alkoxy group, or NR12R13;
- R7 and R11 each independently represent a hydroxyl group, a C1-4 alkyl group, or a C3-6 cycloalkyl group, said C1-4 alkyl group may be substituted with a halogen or CO2R14;
- R8 represents a hydroxyl group, a C1-4 alkoxy group, or NR15R16;
- R9, R10, R12, and R13 each independently represent a hydrogen atom, a C1-4 acyl group, or a C1-4 alkyl group that may be substituted with NR15R16;
- R9 and R10, as well as R12 and R13, taken together with the nitrogen atom to which they are attached, may form a 5- to 6-membered saturated cyclic amine;
- R14 represents a hydrogen atom or a C1-4 alkyl group;
- R15 or R16 each independently represents a hydrogen atom, a C1-4 alkyl, or a C1-4 acyl group;
- R15 and R16, taken together with the nitrogen atom to which they are attached, may form a 5- to 6-membered saturated cyclic amine;
- q represents an integer of 0 to 7;
- provided that when p and q each represent an integer of 2 or more, R1 and R2 each independently may be the same or different;
- a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug of any of these.
20 more elements
A compound, which is:
- (1) N6-(1,3-dimethyl-1H-pyrazol-4-yl)-3-(1H-indol-5-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (2) N6-(1,3-dimethyl-1H-pyrazol-4-yl)-3-(7-fluoro-1H-indazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (3) 3-(7-chloro-1H-indazol-4-yl)-N6-[2-fluoro-4-(methylsulfonyl)phenyl]-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (4) N6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-(1H-indazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (5) 3-(7-fluoro-1H-indazol-4-yl)-N6-[2-fluoro-4-(methylsulfonyl)phenyl]-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- or
- (6) 4-(4-amino-2-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-1H-indazole-7-carbonitrile.
4 more elements
A compound, which is:
- (1) N6-(1,3-dimethyl-1H-pyrazol-4-yl)-3-(1H-indol-5-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (2) N6-(1,3-dimethyl-1H-pyrazol-4-yl)-3-(7-fluoro-1H-indazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (3) 3-(7-chloro-1H-indazol-4-yl)-N6-[2-fluoro-4-(methylsulfonyl)phenyl]-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (4) N6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-(1H-indazol-4-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- (5) 3-(7-fluoro-1H-indazol-4-yl)-N6-[2-fluoro-4-(methylsulfonyl)phenyl]-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine;
- or
- (6) 4-(4-amino-2-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-1H-indazole-7-carbonitrile;
- a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug of any of these.
5 more elements
Dependencies are inferred from the claim text.