Back to results
US 12,679,822 B2Granted
Alkenyl pyrimidine compound, preparation method therefor, and application thereof
AssigneeHongyun Biotech Co., Ltd.
InventorsXianming Deng, Wei Huang, Zhenhua Wu, Yachuang Wu, Caihong Yun, Jianming Zhang, Xin Huang
Life of this patent
Estimating the term…
Abstract
The present invention relates to an alkenyl pyrimidine compound, a preparation method therefor, and an application thereof. Particularly, the present invention relates to a compound having EGFR inhibitory activity and a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, a preparation method thereof, a pharmaceutical composition containing the compound, and a use of the compound in the preparation of drugs for preventing and/or treating cancer and other diseases mediated by EGFR kinase.
Claims11
A compound having the following general formula:
- or a stereoisomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof,
- wherein:
- R1 is selected from:
- 1)
- Y1, Y2, Y3, Y4, Y5 each are independently selected from the following groups, and Y, Y2, Y3, Y4, Y5 are not hydrogen at the same time:
- (1) H, F, Cl, Br, I, nitro, cyano,
- (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorine-containing alkoxy, C3-C6 cycloalkyl,
- (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N—(N-methyl-4-piperidyl) piperazinyl, N—(N-ethyl-4-piperidyl) piperazinyl, 4-(N-methyl-azetidin-3-yl) piperazinyl,
- (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,
- (5) 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-(piperazinyl-1-) piperidyl, 4-(N-methylpiperazinyl-1-) piperidyl, 4-(N-ethylpiperazinyl-1-) piperidyl, 4-(N-isopropylpiperazinyl-1-) piperidyl,
- (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, benzyl,
- (7) 4-(N-methyl-1-piperazinyl) piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl) piperidyl-1-formyl,
- (8) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,
- (9)
- 2)
- wherein Y1, Y3, Y4, Y5 each are independently selected from H, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazinyl-1-) piperidyl, 4-(N-ethylpiperazinyl-1-) piperidyl, or 4-(N-isopropylpiperazinyl-1-) piperidyl, and Y, Y3, Y4, Y5 are not hydrogen at the same time;
- 3)
- wherein, Y1 is selected from H, C1-C6 alkyl, C1-C6 alkoxy, F, Cl, Br, or C1-C6 fluorine-containing alkoxy, Y2, Y5 are H, Ry is selected from C1-C6 alkyl;
- 4)
- wherein, Y1, Y2, Y5 are H, Rz, R each are independently selected from C1-C6 alkyl;
- 5) 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1,5-diethyl-3-pyrazolyl, 1,5-diisopropyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 1-methyl-5-isopropyl-3-pyrazolyl, 1-ethyl-5-methyl-3-pyrazolyl, 1-ethyl-5-isopropyl-3-pyrazolyl, 1-isopropyl-5-methyl-3-pyrazolyl, 1-isopropyl-5-ethyl-3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1,3-dimethyl-4-pyrazolyl, 1,3-diethyl-4-pyrazolyl, 1,3-diisopropyl-4-pyrazolyl, 1-methyl-3-ethyl-4-pyrazolyl, 1-methyl-3-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl, 1-ethyl-3-isopropyl-4-pyrazolyl, 1-isopropyl-3-methyl-4-pyrazolyl, 1-isopropyl-3-ethyl-4-pyrazolyl;
- Z3, Z4 each are independently selected from H, C1-C6 alkyl, C1-C6 fluorine-containing alkyl, or C3-C6 cycloalkyl;
- R3, R4, R5 each are independently selected from H, C1-C6 alkyl, C3-C6 cycloalkyl, or phenyl;
- or,
- R3, R4 and carbon atoms linked thereto together form
- R5 being selected from H, or C1-C6 alkyl.
23 more elements
A compound having the following general formula:
- or a stereoisomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof,
- wherein:
- R1 is selected from:
- 1)
- wherein, Y1, Y2, Y3, Y4, Y5 each are independently selected from the following groups, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:
- (1) H, F, Cl, Br, I, nitro, cyano,
- (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorine-containing alkoxy, C3-C6 cycloalkyl,
- (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,
- (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,
- (5) 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-(N-methylpiperazinyl-1-) piperidyl, 4-(N-ethylpiperazinyl-1-) piperidyl, 4-(N-isopropylpiperazinyl-1-) piperidyl,
- (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,
- (7) 4-(N-methyl-1-piperazinyl) piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl) piperidyl-1-formyl,
- 2)
- wherein:
- Y1, Y3, Y4, Y5 each are independently selected from H, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazinyl-1-) piperidyl, 4-(N-ethylpiperazinyl-1-) piperidyl, or 4-(N-isopropylpiperazinyl-1-) piperidyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time;
- Z5 is selected from C1-C6 alkyl;
- R3, R4, R5 each are independently selected from H, or C1-C6 alkyl.
14 more elements
A compound having the following general formula:
- or a stereoisomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof,
- wherein:
- R1 is selected from:
- 1)
- wherein, Y1, Y2, Y3, Y4, Y5 each are independently selected from the following groups, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:
- (1) H, F, Cl, Br, I, nitro, cyano,
- (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorine-containing alkoxy, C3-C6 cycloalkyl,
- (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,
- (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,
- (5) 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-(N-methylpiperazinyl-1-) piperidyl, 4-(N-ethylpiperazinyl-1-) piperidyl, 4-(N-isopropylpiperazinyl-1-) piperidyl,
- (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,
- (7) 4-(N-methyl-1-piperazinyl) piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl) piperidyl-1-formyl,
- 2)
- wherein:
- Y1, Y3, Y4, Y5 each are independently selected from H, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazinyl-1-) piperidyl, 4-(N-ethylpiperazinyl-1-) piperidyl, or 4-(N-isopropylpiperazinyl-1-) piperidyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time;
- Z6 is selected from C1-C6 alkyl;
- R3, R4, R5 each are independently selected from H, or C1-C6 alkyl.
14 more elements
A compound selected from:
- No.
- Structure
- I-1
- I-2
- I-3
- I-4
- I-5
- I-6
- I-7
- I-8
- I-9
- I-10
- I-11
- I-12
- I-13
- I-14
- II-1
- II-2
- II-3
- II-4
- I-15
- I-16
- I-17
- I-18
- I-19
- I-20
- I-21
- I-22
- I-23
- I-24
- II-16
- II-17
- II-18
- II-19
- II-20
- II-21
- II-22
- II-23
- II-24
- II-25
- II-26
- II-27
- II-28
- II-29
- II-30
- II-31
- II-32
- II-33
- II-34
- II-35
- II-36
- II-37
- II-38
- II-39
- II-40
- II-41
- II-42
- II-43
- II-44
- II-45
- II-46
- II-47
- II-48
- II-49
- II-50
- II-51
- II-52
- II-53
- II-54
- II-55
- II-56
- II-57
- II-58
- II-5
- II-6
- II-7
- II-8
- II-9
- II-10
- II-11
- II-12
- II-13
- II-14
- II-15
- III-1
- III-2
- III-3
- III-4
- III-5
- III-6
- III-7
- II-59
- II-60
- II-61
- II-62
- II-63
- II-64
- II-65
- II-66
- II-67
- II-68
- II-69
- II-70
- II-71
- II-72
- II-73
- II-74
- II-75
- II-76
- II-77
- II-78
- III-8
- III-9
- III-10
- III-11
- III-12
- III-13
- III-14
- III-15
- III-16
- III-17
- III-18
- III-19
- III-20
- III-21
- IV-1
- IV-2
- IV-3
- IV-4
- IV-5
- IV-6
- IV-7
- IV-8
- IV-9
- IV-10
- IV-11
- IV-12
- IV-13
- IV-14
- IV-15
- IV-16
- IV-17
- IV-18
- I-25
- or stereoisomers, pharmaceutically acceptable salts or pharmaceutically acceptable solvates of the above compounds.
142 more elements
A compound having the following general formula or a stereoisomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof:
- wherein:
- R1 is selected from:
- 1)
- wherein:
- Y1, Y2, Y3, Y4, Y5 each are independently selected from the following groups, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:
- H, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-(N-methylpiperazinyl-1-) piperidyl, or N-methyl-4-piperidyl;
- 2)
- wherein:
- Y1, Y3, Y4, Y5 each are independently selected from H, methyl, ethyl, methoxy, or 4-(N-methylpiperazinyl-1-) piperidyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time,
- 3)
- wherein, Y1 is F, Y2, Y5 are H, Ry is methyl;
- wherein, Y1, Y2, Y5 are H, Rz is methyl, R is H;
- Z1, Z2 each are independently selected from C1-C6 alkyl;
- R3, R4, R5 each are independently selected from:
- 1) H, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl;
- 2) substituted or unsubstituted aryl, the substituents being selected from halogen, C1-C6 alkyl, or C3-C8 cycloalkyl;
- 3) R3, R4 and carbon atoms linked thereto together form
- R5 being selected from H, or C1-C6 alkyl;
- and wherein the compound having the general formula (I) does not include
16 more elements
Dependencies are inferred from the claim text.