ALKENYL PYRIMIDINE COMPOUND, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
20230212147 · 2023-07-06
Inventors
- Xianming Deng (Xiamen, CN)
- Wei Huang (Nanjing, CN)
- Zhenhua Wu (Xiamen, CN)
- Yachuang Wu (Beijing, CN)
- Caihong Yun (Beijing, CN)
- Jianming Zhang (Shanghai, CN)
- Xin Huang (Nanjing, CN)
Cpc classification
C07D491/107
CHEMISTRY; METALLURGY
A61K39/3955
HUMAN NECESSITIES
C07F9/5325
CHEMISTRY; METALLURGY
A61K31/675
HUMAN NECESSITIES
A61K31/506
HUMAN NECESSITIES
C07D403/12
CHEMISTRY; METALLURGY
A61K31/55
HUMAN NECESSITIES
International classification
C07F9/53
CHEMISTRY; METALLURGY
A61K31/675
HUMAN NECESSITIES
A61K31/506
HUMAN NECESSITIES
C07D403/12
CHEMISTRY; METALLURGY
A61K31/55
HUMAN NECESSITIES
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.
##STR00001##
Claims
1. A compound having the following general formula: ##STR00424## or a stereoisomer, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, wherein: R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-acetyl-4-piperidyl, N-propionyl-4-piperidyl, N-isopropionyl-4-piperidyl, N-cyclopropylformyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-ethylsulfonyl-4-piperidyl, N-propylsulfonyl-4-piperidyl, N-isopropylsulfonyl-4-piperidyl, N-cyclopropylsulfonyl-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-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-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-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, 1-(N-methyl-4-piperidyl)-4-pyrazolyl, 1-(N-t-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00425## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiomorpholinylethoxy, 2-piperidylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiomorpholinylpropoxy, 3-piperidylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalo-substituted phenylmethoxy, gem-dihalo-substituted phenylmethoxy, hetero-dihalo-substituted phenylmethoxy, (4) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, N-t-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl, (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (7) imidazolyl, 4-methyl-1-imidazolyl, (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(piperazinyl-1-)piperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-acetylpiperazinyl-1-)piperidyl, 4-(N-t-butoxycarbonylpiperazinyl-1-)piperidyl, 4-(N-methylsulfonylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (9) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-acetyl-4-piperidyl, N-t-butoxycarbonyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinylethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (12) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, cyclopropylaminoformyl, cyclobutylaminoformyl, cyclopentylaminoformyl, cyclohexylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylaminoacetyl, cyclobutylaminoacetyl, cyclopentylaminoacetyl, cyclohexylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, iso-propoxyformyl, n-butoxyformyl, iso-butoxyformyl, t-butoxyformyl, (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-sulfonyl, (15) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, cyclopropylaminoformamido, cyclobutylaminoformamido, cyclopentylaminoformamido, piperidyl-1-formamido, 4-hydroxypiperidyl-1-formamido, 4-N,N-dimethylpiperidyl-1-formamido, 4-N,N-diethylpiperidyl-1-formamido, tetrahydropyrrolyl-1-formamido, 3-N,N-dimethyltetrahydropyrrolyl-1-formamido, 3-N,N-diethyltetrahydropyrrolyl-1-formamido, N-methylpiperazinyl-1-formamido, N-ethylpiperazinyl-1-formamido, N-acetylpiperazinyl-1-formamido, N-t-butoxycarbonylpiperazinyl-1-formamido, N-(2-hydroxyethyl)piperazinyl-1-formamido, N-(2-cyanoethyl)piperazinyl-1-formamido, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formamido, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formamido, N-(3-hydroxypropyl)piperazinyl-1-formamido, N-(3-N,N-dimethylpropyl)piperazinyl-1-formamido, N-(3-N,N-diethylpropyl)piperazinyl-1-formamido, morpholinyl-1-formamido, 3,5-dimethylmorpholinyl-1-formamido, 4-(tetrahydropyrrolyl)piperidyl-1-formamido, 4-(N-methyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-acetyl-1-piperazinyl)piperidyl-1-formamido, N-(N-methyl-4-piperidyl)piperazinyl-1-formamido, (16) ##STR00426## ##STR00427## (17) Y.sub.3 and Y.sub.4 may form an oxygen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1, (18) Y.sub.3 and Y.sub.4 may form a nitrogen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1; 5) ##STR00428## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not-hydrogen at the same time; 6) ##STR00429## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00430## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00431## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; preferably, R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-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-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-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, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00432## Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) imidazolyl, 4-methyl-1-imidazolyl, (7) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(piperazinyl-1-)piperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (8) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (9) 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-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (10) 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (11) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, (13) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, (14) ##STR00433## ##STR00434## 5) ##STR00435## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00436## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00437## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00438## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; 9) ##STR00439## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.x is selected from the same substituents as described above for Y.sub.1; 10) ##STR00440## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.y is selected from the same substituents as described above for Y.sub.1; 11) ##STR00441## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.z, R each are independently selected from the same substituents as described above for Y.sub.1; more preferably, R.sup.1 is selected from: 1) ##STR00442## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.6 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) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-(piperazinyl-1-)piperidyl, 4-hydroxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, (7) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, (8) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, 2-(N,N-dimethylamino)acetamido, cyclopropylsulfamido, 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) 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (10) 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, (11) cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, (12) 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, ##STR00443## ##STR00444## 2) ##STR00445## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, or 4-(N-isopropylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 3) ##STR00446## wherein, Y.sub.1 is selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, F, Cl, Br, or C.sub.1-C.sub.6 fluorine-containing alkoxy, Y.sub.2, Y.sub.5 each are independently selected from H, or C.sub.1-C.sub.6 alkyl (preferably H), R.sup.y is selected from C.sub.1-C.sub.6 alkyl; 4) ##STR00447## wherein, Y.sub.1, Y.sub.2, Y.sub.5 each are independently selected from H, or C.sub.1-C.sub.6 alkyl (preferably H), R.sup.Z is selected from C.sub.1-C.sub.6 alkyl, R is selected from H, or C.sub.1-C.sub.6 alkyl (preferably selected from H, or methyl); 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; most preferably, R.sup.1 is selected from: 1) ##STR00448## wherein, Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: H, F, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, iso-propoxy, trifluoromethyl, trifluoromethoxy, vinyl, N-methylpiperazinyl, morpholinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-hydroxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, N-methyl-4-piperidyl, 2-(N,N-dimethylamino)acetamido, cyclopropylsulfamido, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, 4-methyl-1-piperazinylmethylene, benzyl, cyclopropylmethylene, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, cyclopropylaminosulfonyl, N-methylpiperazinyl-1-sulfonyl, 4-(piperazinyl-1-)piperidyl, N-(N-methyl-4-piperidyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, ##STR00449## 2) ##STR00450## wherein, Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, methyl, ethyl, methoxy, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methylpiperazinyl, or 4-(N-methylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 3) ##STR00451## wherein, Y.sub.1 is selected from H, methyl, methoxy, F, C.sub.1, or trifluoromethoxy, Y.sub.2, Y.sub.5 are H, R.sup.y is methyl; 4) ##STR00452## wherein, Y.sub.1, Y.sub.2, Y.sub.5 are H, R.sup.z is methyl, R is selected from H, or methyl; 5) 3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl; R.sup.2 is selected from: 1) ##STR00453## wherein, Z.sub.1, Z.sub.2 each are independently selected from C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; preferably, Z.sub.1, Z.sub.2 each are independently selected from C.sub.1-C.sub.6 alkyl; more preferably, Z.sub.1, Z.sub.2 are methyl; 2) ##STR00454## wherein, Z.sub.3, Z.sub.4 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, or C.sub.3-C.sub.6 fluorine-containing cycloalkyl, and Z.sub.4 is not H; preferably, Z.sub.3, Z.sub.4 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, or C.sub.3-C.sub.6 cycloalkyl; more preferably, Z.sub.3, Z.sub.4 each are independently selected from H, methyl, ethyl, isopropyl, cyclopropyl, or trifluoromethyl; 3) ##STR00455## wherein, Z.sub.5 is selected from C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, or C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; preferably, Z.sub.5 is selected from C.sub.1-C.sub.6 alkyl; more preferably, Z.sub.5 is selected from methyl, or isopropyl; 4) ##STR00456## wherein, Z.sub.6, Z.sub.7 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, or C.sub.3-C.sub.6 fluorine-containing cycloalkyl, or, Z.sub.6, Z.sub.7, together with N, may form a 1 to 2 heteroatom-containing substituted or unsubstituted 4- to 8-membered ring, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; preferably, Z.sub.6, Z.sub.7 each are independently selected from H, or C.sub.1-C.sub.6 alkyl; more preferably, Z.sub.6, Z.sub.7 each are independently selected from H, methyl, or isopropyl, most preferably, in Z.sub.6 and Z.sub.7, one is H, and the other is selected from methyl, or isopropyl; R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 fluorine-containing cycloalkyl, C.sub.3-C.sub.6 oxygen-containing cycloalkyl; 2) substituted or unsubstituted aryl or heteroaryl, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form a substituted or unsubstituted 5- to 7-membered ring, the substituent being selected from halogen, or C.sub.1-C.sub.6 alkyl, R.sup.5 is selected from H, or C.sub.1-C.sub.6 alkyl; preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.6 cycloalkyl; 2) substituted or unsubstituted aryl, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00457## R.sup.5 being selected from H, or C.sub.1-C.sub.6 alkyl; more preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, methyl, ethoxy, cyclopropyl; 2) phenyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00458## R.sup.5 being H; wherein, the compound having the general formula (A) does not include ##STR00459##
2. The compound according to claim 1, having the following general formula: ##STR00460## or a stereoisomer, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, wherein: R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-acetyl-4-piperidyl, N-propionyl-4-piperidyl, N-isopropionyl-4-piperidyl, N-cyclopropylformyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-ethylsulfonyl-4-piperidyl, N-propylsulfonyl-4-piperidyl, N-isopropylsulfonyl-4-piperidyl, N-cyclopropylsulfonyl-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidyl)-4-pyrazolyl, 1-(N-t-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00461## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiomorpholinylethoxy, 2-piperidylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiomorpholinylpropoxy, 3-piperidylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalo-substituted phenylmethoxy, gem-dihalo-substituted phenylmethoxy, hetero-dihalo-substituted phenylmethoxy, (4) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-t-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl, (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (7) imidazolyl, 4-methyl-1-imidazolyl, (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-acetylpiperazinyl-1-)piperidyl, 4-(N-t-butoxycarbonylpiperazinyl-1-)piperidyl, 4-(N-methylsulfonylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (9) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-acetyl-4-piperidyl, N-t-butoxycarbonyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinylethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (12) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, cyclopropylaminoformyl, cyclobutylaminoformyl, cyclopentylaminoformyl, cyclohexylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylaminoacetyl, cyclobutylaminoacetyl, cyclopentylaminoacetyl, cyclohexylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, iso-propoxyformyl, n-butoxyformyl, iso-butoxyformyl, t-butoxyformyl, (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-sulfonyl, (15) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, cyclopropylaminoformamido, cyclobutylaminoformamido, cyclopentylaminoformamido, piperidyl-1-formamido, 4-hydroxypiperidyl-1-formamido, 4-N,N-dimethylpiperidyl-1-formamido, 4-N,N-diethylpiperidyl-1-formamido, tetrahydropyrrolyl-1-formamido, 3-N,N-dimethyltetrahydropyrrolyl-1-formamido, 3-N,N-diethyltetrahydropyrrolyl-1-formamido, N-methylpiperazinyl-1-formamido, N-ethylpiperazinyl-1-formamido, N-acetylpiperazinyl-1-formamido, N-t-butoxycarbonylpiperazinyl-1-formamido, N-(2-hydroxyethyl)piperazinyl-1-formamido, N-(2-cyanoethyl)piperazinyl-1-formamido, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formamido, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formamido, N-(3-hydroxypropyl)piperazinyl-1-formamido, N-(3-N,N-dimethylpropyl)piperazinyl-1-formamido, N-(3-N,N-diethylpropyl)piperazinyl-1-formamido, morpholinyl-1-formamido, 3,5-dimethylmorpholinyl-1-formamido, 4-(tetrahydropyrrolyl)piperidyl-1-formamido, 4-(N-methyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-acetyl-1-piperazinyl)piperidyl-1-formamido, N-(N-methyl-4-piperidyl)piperazinyl-1-formamido, (16) Y.sub.3 and Y.sub.4 may form an oxygen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1, (17) Y.sub.3 and Y.sub.4 may form a nitrogen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1; 5) ##STR00462## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00463## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00464## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00465## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; preferably, R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00466## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) imidazolyl, 4-methyl-1-imidazolyl, (7) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (8) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (10) 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (11) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, (13) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido; 5) ##STR00467## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00468## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00469## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00470## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; 9) ##STR00471## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.x is selected from the same substituents as described above for Y.sub.1; 10) ##STR00472## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.y is selected from the same substituents as described above for Y.sub.1; 11) ##STR00473## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.z, R each are independently selected from the same substituents as described above for Y.sub.1; more preferably-R.sup.1 is selected from: 1) ##STR00474## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 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)piperidin-4-yl N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl; 2) ##STR00475## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, or 4-(N-isopropylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 3) ##STR00476## wherein, Y.sub.1 is selected from F, C.sub.1, or Br, Y.sub.2, Y.sub.5 each are independently selected from H, or C.sub.1-C.sub.6 alkyl (preferably H), R.sup.y is selected from C.sub.1-C.sub.6 alkyl; 4) ##STR00477## wherein, Y.sub.1, Y.sub.2, Y.sub.5 each are independently selected from H, or C.sub.1-C.sub.6 alkyl (preferably H), R.sup.Z is selected from C.sub.1-C.sub.6 alkyl, R is selected from H, or C.sub.1-C.sub.6 alkyl (preferably H); most preferably, R.sup.1 is selected from: 1) ##STR00478## wherein: Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 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; preferably, Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 each are independently selected from H, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, or N-methyl-4-piperidyl; Y.sub.3 is selected from H, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, or 4-(N-methylpiperazinyl-1-)piperidyl; 2) ##STR00479## wherein: Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, methyl, ethyl, methoxy, or 4-(N-methylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time, preferably, Y.sub.1, Y.sub.4, Y.sub.5 each are independently selected from H, methyl, ethyl, or methoxy, Y.sub.3 is 4-N-methylpiperazinyl-1-)piperidyl; 3) ##STR00480## wherein, Y.sub.1 is F, Y.sub.2, Y.sub.5 are H, R.sup.y is methyl; 4) ##STR00481## wherein, Y.sub.1, Y.sub.2, Y.sub.5 are H, R.sup.z is methyl, R is H; Z.sub.1, Z.sub.2 each are independently selected from C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; preferably, Z.sub.1, Z.sub.2 each are independently selected from C.sub.1-C.sub.6 alkyl; more preferably, Z.sub.1, Z.sub.2 are methyl; R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 fluorine-containing cycloalkyl, C.sub.3-C.sub.6 oxygen-containing cycloalkyl; 2) substituted or unsubstituted aryl or heteroaryl, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form a substituted or unsubstituted 5- to 7-membered ring, the substituent being selected from halogen, or C.sub.1-C.sub.6 alkyl, R.sup.5 is selected from H, or C.sub.1-C.sub.6 alkyl; preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.6 cycloalkyl; 2) substituted or unsubstituted aryl, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00482## R.sup.5 being selected from H, or C.sub.1-C.sub.6 alkyl; more preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, methyl, ethoxy, cyclopropyl; 2) phenyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00483## R.sup.5 being H; most preferably, R.sup.3 is selected from H, or methyl, R.sup.4 is selected from H, methyl, ethoxy, cyclopropyl, or phenyl, R.sup.5 is selected from H, or methyl; or, R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00484## R.sup.5 being H.
3. The compound according to claim 1, having the following general formula: ##STR00485## or a stereoisomer, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, wherein: R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-acetyl-4-piperidyl, N-propionyl-4-piperidyl, N-isopropionyl-4-piperidyl, N-cyclopropylformyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-ethylsulfonyl-4-piperidyl, N-propylsulfonyl-4-piperidyl, N-isopropylsulfonyl-4-piperidyl, N-cyclopropylsulfonyl-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-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-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-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, 1-(N-methyl-4-piperidyl)-4-pyrazolyl, 1-(N-t-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00486## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiomorpholinylethoxy, 2-piperidylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiomorpholinylpropoxy, 3-piperidylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalo-substituted phenylmethoxy, gem-dihalo-substituted phenylmethoxy, hetero-dihalo-substituted phenylmethoxy, (4) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, N-t-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl, (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (7) imidazolyl, 4-methyl-1-imidazolyl, (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(piperazinyl-1-)piperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-acetylpiperazinyl-1-)piperidyl, 4-(N-t-butoxycarbonylpiperazinyl-1-)piperidyl, 4-(N-methylsulfonylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (9) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-acetyl-4-piperidyl, N-t-butoxycarbonyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinylethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (12) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, cyclopropylaminoformyl, cyclobutylaminoformyl, cyclopentylaminoformyl, cyclohexylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylaminoacetyl, cyclobutylaminoacetyl, cyclopentylaminoacetyl, cyclohexylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, iso-propoxyformyl, n-butoxyformyl, iso-butoxyformyl, t-butoxyformyl, (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-sulfonyl, (15) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, cyclopropylaminoformamido, cyclobutylaminoformamido, cyclopentylaminoformamido, piperidyl-1-formamido, 4-hydroxypiperidyl-1-formamido, 4-N,N-dimethylpiperidyl-1-formamido, 4-N,N-diethylpiperidyl-1-formamido, tetrahydropyrrolyl-1-formamido, 3-N,N-dimethyltetrahydropyrrolyl-1-formamido, 3-N,N-diethyltetrahydropyrrolyl-1-formamido, N-methylpiperazinyl-1-formamido, N-ethylpiperazinyl-1-formamido, N-acetylpiperazinyl-1-formamido, N-t-butoxycarbonylpiperazinyl-1-formamido, N-(2-hydroxyethyl)piperazinyl-1-formamido, N-(2-cyanoethyl)piperazinyl-1-formamido, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formamido, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formamido, N-(3-hydroxypropyl)piperazinyl-1-formamido, N-(3-N,N-dimethylpropyl)piperazinyl-1-formamido, N-(3-N,N-diethylpropyl)piperazinyl-1-formamido, morpholinyl-1-formamido, 3,5-dimethylmorpholinyl-1-formamido, 4-(tetrahydropyrrolyl)piperidyl-1-formamido, 4-(N-methyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-acetyl-1-piperazinyl)piperidyl-1-formamido, N-(N-methyl-4-piperidyl)piperazinyl-1-formamido, (16) ##STR00487## ##STR00488## (17) Y.sub.3 and Y.sub.4 may form an oxygen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1, (18) Y.sub.3 and Y.sub.4 may form a nitrogen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1; 5) ##STR00489## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00490## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00491## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00492## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; preferably, R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-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-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-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, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00493## Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) imidazolyl, 4-methyl-1-imidazolyl, (7) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(piperazinyl-1-)piperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (8) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (9) 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-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (10) 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (11) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, (13) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, (14) ##STR00494## ##STR00495## 5) ##STR00496## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00497## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00498## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00499## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; 9) ##STR00500## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.x is selected from the same substituents as described above for Y.sub.1; 10) ##STR00501## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.y is selected from the same substituents as described above for Y.sub.1; 11) ##STR00502## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.z, R each are independently selected from the same substituents as described above for Y.sub.1; more preferably, R.sup.1 is selected from: 1) ##STR00503## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 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) ##STR00504## ##STR00505## 2) ##STR00506## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, or 4-(N-isopropylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 3) ##STR00507## wherein, Y.sub.1 is selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, F, Cl, Br, or C.sub.1-C.sub.6 fluorine-containing alkoxy, Y.sub.2, Y.sub.5 are H, R.sup.y is selected from C.sub.1-C.sub.6 alkyl; 4) ##STR00508## wherein, Y.sub.1, Y.sub.2, Y.sub.5 are H, R.sup.z, R each are independently selected from C.sub.1-C.sub.6 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; most preferably, R.sup.1 is selected from: 1) ##STR00509## wherein: Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: H, F, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, benzyl, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, 4-(piperazinyl-1-)piperidyl, N-(N-methyl-4-piperidyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, ##STR00510## preferably, Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 each are independently selected from H, F, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, or benzyl; Y.sub.3 is selected from F, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, 4-(piperazinyl-1-)piperidyl, N-(N-methyl-4-piperidyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, ##STR00511## 2) ##STR00512## wherein: Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, ethyl, methoxy, or 4-(N-methylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time, preferably, Y.sub.1, Y.sub.4, Y.sub.5 each are independently selected from H, ethyl, or methoxy, Y.sub.3 is 4-(N-methylpiperazinyl-1-)piperidyl; 3) ##STR00513## wherein, Y.sub.1 is selected from H, methyl, methoxy, F, C.sub.1, or trifluoromethoxy, Y.sub.2, Y.sub.5 are H, R.sup.y is methyl; 4) ##STR00514## wherein, Y.sub.1, Y.sub.2, Y.sub.5 are H, R.sup.z, R are methyl; 5) 3-pyrazoyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl; Z.sub.3, Z.sub.4 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, or C.sub.3-C.sub.6 fluorine-containing cycloalkyl, and Z.sub.4 is not H; preferably, Z.sub.3, Z.sub.4 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, or C.sub.3-C.sub.6 cycloalkyl; more preferably, Z.sub.3, Z.sub.4 each are independently selected from H, methyl, ethyl, isopropyl, cyclopropyl, or trifluoromethyl; most preferably, Z.sub.3 is selected from H, methyl, ethyl, isopropyl, or cyclopropyl, Z.sub.4 is selected from methyl, ethyl, isopropyl, cyclopropyl, or trifluoromethyl; R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 fluorine-containing cycloalkyl, C.sub.3-C.sub.6 oxygen-containing cycloalkyl; 2) substituted or unsubstituted aryl or heteroaryl, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form a substituted or unsubstituted 5- to 7-membered ring, the substituent being selected from halogen, or C.sub.1-C.sub.6 alkyl, R.sup.5 is selected from H, or C.sub.1-C.sub.6 alkyl; preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, or phenyl; or, R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00515## R.sup.5 being selected from H, or C.sub.1-C.sub.6 alkyl; more preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from H, methyl, cyclopropyl, or phenyl; or, R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00516## R.sup.5 being H; most preferably, R.sup.3 is selected from H, or methyl, R.sup.4 is selected from H, methyl, cyclopropyl, or phenyl, R.sup.5 is selected from H, or methyl; or, R.sup.3, R.sup.4 and carbon atoms linked thereto together form ##STR00517## R.sup.5 being H.
4. The compound according to claim 1, having the following general formula: ##STR00518## or a stereoisomer, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, wherein: R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-acetyl-4-piperidyl, N-propionyl-4-piperidyl, N-isopropionyl-4-piperidyl, N-cyclopropylformyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-ethylsulfonyl-4-piperidyl, N-propylsulfonyl-4-piperidyl, N-isopropylsulfonyl-4-piperidyl, N-cyclopropylsulfonyl-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidyl)-4-pyrazolyl, 1-(N-t-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00519## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiomorpholinylethoxy, 2-piperidylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiomorpholinylpropoxy, 3-piperidylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalo-substituted phenylmethoxy, gem-dihalo-substituted phenylmethoxy, hetero-dihalo-substituted phenylmethoxy, (4) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-t-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl, (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (7) imidazolyl, 4-methyl-1-imidazolyl, (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-acetylpiperazinyl-1-)piperidyl, 4-(N-t-butoxycarbonylpiperazinyl-1-)piperidyl, 4-(N-methylsulfonylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (9) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-acetyl-4-piperidyl, N-t-butoxycarbonyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinylethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (12) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, cyclopropylaminoformyl, cyclobutylaminoformyl, cyclopentylaminoformyl, cyclohexylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylaminoacetyl, cyclobutylaminoacetyl, cyclopentylaminoacetyl, cyclohexylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, iso-propoxyformyl, n-butoxyformyl, iso-butoxyformyl, t-butoxyformyl, (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-sulfonyl, (15) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, cyclopropylaminoformamido, cyclobutylaminoformamido, cyclopentylaminoformamido, piperidyl-1-formamido, 4-hydroxypiperidyl-1-formamido, 4-N,N-dimethylpiperidyl-1-formamido, 4-N,N-diethylpiperidyl-1-formamido, tetrahydropyrrolyl-1-formamido, 3-N,N-dimethyltetrahydropyrrolyl-1-formamido, 3-N,N-diethyltetrahydropyrrolyl-1-formamido, N-methylpiperazinyl-1-formamido, N-ethylpiperazinyl-1-formamido, N-acetylpiperazinyl-1-formamido, N-t-butoxycarbonylpiperazinyl-1-formamido, N-(2-hydroxyethyl)piperazinyl-1-formamido, N-(2-cyanoethyl)piperazinyl-1-formamido, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formamido, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formamido, N-(3-hydroxypropyl)piperazinyl-1-formamido, N-(3-N,N-dimethylpropyl)piperazinyl-1-formamido, N-(3-N,N-diethylpropyl)piperazinyl-1-formamido, morpholinyl-1-formamido, 3,5-dimethylmorpholinyl-1-formamido, 4-(tetrahydropyrrolyl)piperidyl-1-formamido, 4-(N-methyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-acetyl-1-piperazinyl)piperidyl-1-formamido, N-(N-methyl-4-piperidyl)piperazinyl-1-formamido, (16) Y.sub.3 and Y.sub.4 may form an oxygen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1, (17) Y.sub.3 and Y.sub.4 may form a nitrogen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1; 5) ##STR00520## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00521## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00522## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00523## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; preferably, R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00524## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) imidazolyl, 4-methyl-1-imidazolyl, (7) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (8) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (10) 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (11) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, (13) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido; 5) ##STR00525## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00526## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00527## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00528## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; 9) ##STR00529## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.x is selected from the same substituents as described above for Y.sub.1; 10) ##STR00530## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.y is selected from the same substituents as described above for Y.sub.1; 11) ##STR00531## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.z, R each are independently selected from the same substituents as described above for Y.sub.1; more preferably, R.sup.1 is selected from: 1) ##STR00532## wherein, Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 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) ##STR00533## wherein: Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, or 4-(N-isopropylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; most preferably, R.sup.1 is selected from: 1) ##STR00534## wherein, Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: H, F, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, or 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl; preferably, Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 each are independently selected from H, F, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, or cyclopropylmethylene; Y.sub.3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, or 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl; 2) ##STR00535## wherein: Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, ethyl, methoxy, or 4-(N-methylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time, preferably, Y.sub.1, Y.sub.4, Y.sub.5 each are independently selected from H, ethyl, or methoxy, Y.sub.3 is 4-(N-methylpiperazinyl-1-)piperidyl; Z.sub.5 is selected from C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, or C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; preferably, Z.sub.5 is selected from C.sub.1-C.sub.6 alkyl; more preferably, Z.sub.5 is selected from methyl, or isopropyl; R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 fluorine-containing cycloalkyl, C.sub.3-C.sub.6 oxygen-containing cycloalkyl; 2) substituted or unsubstituted aryl or heteroaryl, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form a substituted or unsubstituted 5- to 7-membered ring, the substituent being selected from halogen, or C.sub.1-C.sub.6 alkyl, R.sup.5 is selected from H, or C.sub.1-C.sub.6 alkyl; preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from H, or C.sub.1-C.sub.6 alkyl; more preferably, R.sup.3, R.sup.4, R.sup.5 are H.
5. The compound according to claim 1, having the following general formula: ##STR00536## or a stereoisomer, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, wherein: R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-acetyl-4-piperidyl, N-propionyl-4-piperidyl, N-isopropionyl-4-piperidyl, N-cyclopropylformyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-ethylsulfonyl-4-piperidyl, N-propylsulfonyl-4-piperidyl, N-isopropylsulfonyl-4-piperidyl, N-cyclopropylsulfonyl-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidyl)-4-pyrazolyl, 1-(N-t-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00537## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiomorpholinylethoxy, 2-piperidylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiomorpholinylpropoxy, 3-piperidylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalo-substituted phenylmethoxy, gem-dihalo-substituted phenylmethoxy, hetero-dihalo-substituted phenylmethoxy, (4) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-t-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl, (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (7) imidazolyl, 4-methyl-1-imidazolyl, (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-acetylpiperazinyl-1-)piperidyl, 4-(N-t-butoxycarbonylpiperazinyl-1-)piperidyl, 4-(N-methylsulfonylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (9) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-acetyl-4-piperidyl, N-t-butoxycarbonyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinylethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (12) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, cyclopropylaminoformyl, cyclobutylaminoformyl, cyclopentylaminoformyl, cyclohexylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylaminoacetyl, cyclobutylaminoacetyl, cyclopentylaminoacetyl, cyclohexylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, iso-propoxyformyl, n-butoxyformyl, iso-butoxyformyl, t-butoxyformyl, (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-sulfonyl, (15) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido, cyclopropylaminoformamido, cyclobutylaminoformamido, cyclopentylaminoformamido, piperidyl-1-formamido, 4-hydroxypiperidyl-1-formamido, 4-N,N-dimethylpiperidyl-1-formamido, 4-N,N-diethylpiperidyl-1-formamido, tetrahydropyrrolyl-1-formamido, 3-N,N-dimethyltetrahydropyrrolyl-1-formamido, 3-N,N-diethyltetrahydropyrrolyl-1-formamido, N-methylpiperazinyl-1-formamido, N-ethylpiperazinyl-1-formamido, N-acetylpiperazinyl-1-formamido, N-t-butoxycarbonylpiperazinyl-1-formamido, N-(2-hydroxyethyl)piperazinyl-1-formamido, N-(2-cyanoethyl)piperazinyl-1-formamido, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formamido, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formamido, N-(3-hydroxypropyl)piperazinyl-1-formamido, N-(3-N,N-dimethylpropyl)piperazinyl-1-formamido, N-(3-N,N-diethylpropyl)piperazinyl-1-formamido, morpholinyl-1-formamido, 3,5-dimethylmorpholinyl-1-formamido, 4-(tetrahydropyrrolyl)piperidyl-1-formamido, 4-(N-methyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formamido, 4-(N-acetyl-1-piperazinyl)piperidyl-1-formamido, N-(N-methyl-4-piperidyl)piperazinyl-1-formamido, (16) Y.sub.3 and Y.sub.4 may form an oxygen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1, (17) Y.sub.3 and Y.sub.4 may form a nitrogen-containing substituted or unsubstituted 5- to 7-membered ring; the substituent may be selected from the same substituents as described above for Y.sub.1; 5) ##STR00538## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00539## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00540## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00541## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; preferably, R.sup.1 is selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.1-C.sub.6 heteroatom-containing alkyl, C.sub.3-C.sub.8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-iso-propoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) ##STR00542## Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) imidazolyl, 4-methyl-1-imidazolyl, (7) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, 4-(N-isopropylpiperazinyl-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazinyl-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazinyl-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazinyl-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazinyl-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazinyl-1-)piperidyl, 4-(tetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl-1-)piperidyl, 4-(3-N,N-diethylaminotetrahydropyrrolyl-1-)piperidyl, (8) piperidin-4-yl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-isopropyl-4-piperidyl, N-(2-hydroxyethyl)-4-piperidyl, N-(2-N,N-dimethylaminoethyl)-4-piperidyl, N-(2-N,N-diethylaminoethyl)-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-(3-hydroxypropyl)-4-piperidyl, N-(3-N,N-dimethylaminopropyl)-4-piperidyl, N-(3-N,N-diethylaminopropyl)-4-piperidyl, N-(3-cyanopropyl)-4-piperidyl, N-cyanomethylene-4-piperidyl, (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidyl-4-amino, N-ethylpiperidyl-4-amino, N-n-propylpiperidyl-4-amino, N-isopropylpiperidyl-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methylsulfamido, ethylsulfamido, n-propylsulfamido, isopropylsulfamido, cyclopropylsulfamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (10) 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidyl-1-methylene, 4-(N,N-dimethylamino)-1-piperidylmethylene, 4-hydroxypiperidyl-1-methylene, tetrahydropyrrolyl-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrolylmethylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, (11) aminoformyl, methylaminoformyl, N,N-dimethylaminoformyl, ethylaminoformyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, tetrahydropyrrolyl-1-formyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-formyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-formyl, morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, piperidyl-1-formyl, 4-hydroxypiperidyl-1-formyl, 4-(N,N-dimethylamino)piperidyl-1-formyl, 4-(N,N-diethylamino)piperidyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidyl-1-formyl, N-methylpiperazinyl-1-formyl, N-ethylpiperazinyl-1-formyl, N-isopropylpiperazinyl-1-formyl, N-(2-hydroxyethyl)piperazinyl-1-formyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formyl, 4-(N-methyl-4-piperidyl)piperazinyl-1-formyl, 4-(N-ethyl-4-piperidyl)piperazinyl-1-formyl, (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrolyl-1-sulfonyl, morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, piperidyl-1-sulfonyl, 4-hydroxypiperidyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidyl-1-sulfonyl, 4-(N,N-diethylamino)piperidyl-1-sulfonyl, N-methylpiperazinyl-1-sulfonyl, N-ethylpiperazinyl-1-sulfonyl, N-isopropylpiperazinyl-1-sulfonyl, N-(2-hydroxyethyl)piperazinyl-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazinyl-1-sulfonyl, (13) aminoformamido, methylaminoformamido, ethylaminoformamido, propylaminoformamido, isopropylaminoformamido; 5) ##STR00543## wherein Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 6) ##STR00544## wherein Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; 7) ##STR00545## wherein Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 may be hydrogen at the same time; 8) ##STR00546## wherein Y.sub.1, Y.sub.3, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.3, Y.sub.5 are not hydrogen at the same time; 9) ##STR00547## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.x is selected from the same substituents as described above for Y.sub.1; 10) ##STR00548## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.y is selected from the same substituents as described above for Y.sub.1; 11) ##STR00549## wherein Y.sub.1, Y.sub.2, Y.sub.5 are the same as defined in 4), and Y.sub.1, Y.sub.2, Y.sub.5 may be hydrogen at the same time, R.sup.z, R each are independently selected from the same substituents as described above for Y.sub.1; more preferably R.sup.1 is selected from: 1) ##STR00550## wherein, Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: (1) H, F, Cl, Br, I, nitro, cyano, (2) C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkoxy, C.sub.3-C.sub.6 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) ##STR00551## wherein: Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, 4-(N-methylpiperazinyl-1-)piperidyl, 4-(N-ethylpiperazinyl-1-)piperidyl, or 4-(N-isopropylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time; most preferably, R.sup.1 is selected from: 1) ##STR00552## wherein, Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from the following groups, and Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time: H, F, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, or 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl; preferably, Y.sub.1, Y.sub.2, Y.sub.4, Y.sub.5 each are independently selected from H, F, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, or cyclopropylmethylene; Y.sub.3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidyl, 4-(N-methylpiperazinyl-1-)piperidyl, or 4-(N-methyl-1-piperazinyl)piperidyl-1-formyl; 2) ##STR00553## wherein: Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 each are independently selected from H, ethyl, methoxy, or 4-(N-methylpiperazinyl-1-)piperidyl, and Y.sub.1, Y.sub.3, Y.sub.4, Y.sub.5 are not hydrogen at the same time, preferably, Y.sub.1, Y.sub.4, Y.sub.5 each are independently selected from H, ethyl, or methoxy, Y.sub.3 is 4-(N-methylpiperazinyl-1-)piperidyl; Z.sub.6 is selected from C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluorine-containing alkyl, or C.sub.3-C.sub.6 cycloalkyl; preferably, Z.sub.6 is selected from C.sub.1-C.sub.6 alkyl; more preferably, Z.sub.6 is selected from methyl, or isopropyl; R.sup.3, R.sup.4, R.sup.5 each are independently selected from: 1) H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluorine-containing alkyl, C.sub.1-C.sub.6 oxygen-containing alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 fluorine-containing cycloalkyl, C.sub.3-C.sub.6 oxygen-containing cycloalkyl; 2) substituted or unsubstituted aryl or heteroaryl, the substituents being selected from halogen, C.sub.1-C.sub.6 alkyl, or C.sub.3-C.sub.8 cycloalkyl; 3) R.sup.3, R.sup.4 and carbon atoms linked thereto together form a substituted or unsubstituted 5- to 7-membered ring, the substituent being selected from halogen, or C.sub.1-C.sub.6 alkyl, R.sup.5 is selected from H, or C.sub.1-C.sub.6 alkyl; preferably, R.sup.3, R.sup.4, R.sup.5 each are independently selected from H, or C.sub.1-C.sub.6 alkyl; more preferably, R.sup.3, R.sup.4, R.sup.5 are H.
6. The compound according to claim 1, which is selected from: TABLE-US-00003 No. Structure I-1
7. A method of preparing the compound according to claim 1, comprising the following steps: ##STR00696## wherein, the definitions of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as described in claim 1, X is halogen, reaction conditions are as follows: (a) a nucleophilic substitution reaction under acidic or alkaline condition; (b) a coupling reaction catalyzed by metal palladium, or a nucleophilic substitution reaction under acidic condition; (c) a coupling reaction catalyzed by metal palladium; wherein: the metal palladium catalyst is selected from palladium acetate, tetrakis(triphenylphosphine) palladium, bistriphenylphosphine palladium dichloride, [1,1′-bis(diphenylphosphino)ferrocene] palladium dichloride or tris(dibenzylideneacetone) dipalladium; the alkaline condition refers to a condition in which any of the following substances exists: triethylamine, diisopropylethylamine, pyridine, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydride, or potassium hydride; the acidic condition refers to a condition in which any of the following substances exists: acetic acid, trifluoroacetic acid, hydrochloric acid, methanesulfonic acid, p-toluene sulfonic acid, or camphorsulfonic acid.
8. A pharmaceutical composition comprising the compound according to claim 1 or a stereoisomer, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof and optionally a pharmaceutically acceptable excipient, preferably, the pharmaceutical composition further comprises a EGFR monoclonal antibody; preferably, the EGFR monoclonal antibody is Cetuximab or biosimilars thereof.
9. (canceled)
10. A method of preventing and/or treating EGFR kinase-mediated cancers and other diseases, comprising administering a preventively effective amount and/or a therapeutically effective amount of the compound according to claim 1, or a stereoisomer thereof, a prodrug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof to a subject in need, preferably, the method is for preventing and/or treating lung cancer (preferably non-small cell lung cancer); more preferably, the method is for preventing and/or treating mutation-type lung cancer (preferably non-small cell lung cancer) with 19Del, L858R, T790M, or C797S mutation or a combination thereof of EGFR kinase; most preferably, the method is for preventing and/or treating lung cancer (preferably non-small cell lung cancer) with 19Del single mutation, L858R single mutation, 19Del/T790M dual mutation, L858R/T790M dual mutation, 19Del/T790M/C797S triple mutation or L858R/T790M/C797S triple mutation of EGFR kinase.
11. (canceled)
12. A method of preventing and/or treating EGFR kinase-mediated cancers and other diseases, comprising administering a preventively effective amount and/or a therapeutically effective amount of the pharmaceutical composition according to claim 8 to a subject in need, preferably, the method is for preventing and/or treating lung cancer (preferably non-small cell lung cancer); more preferably, the method is for preventing and/or treating mutation-type lung cancer (preferably non-small cell lung cancer) with 19Del, L858R, T790M, or C797S mutation or a combination thereof of EGFR kinase; most preferably, the method is for preventing and/or treating lung cancer (preferably non-small cell lung cancer) with 19Del single mutation, L858R single mutation, 19Del/T790M dual mutation, L858R/T790M dual mutation, 19Del/T790M/C797S triple mutation or L858R/T790M/C797S triple mutation of EGFR kinase.
Description
MODE OF CARRYING OUT THE INVENTION
[0891] The embodiments of the present invention are described in detail below by way of specific examples, but in any case they cannot be construed as limiting the present invention.
[0892] Compounds may be divided into the following four classes:
##STR00215##
[0893] wherein, R.sup.1, R.sup.3, R.sup.4, R.sup.5, Z.sub.1, Z.sub.2, Z.sub.3, Z.sub.4, Z.sub.5 are as above described.
[0894] Some of the raw materials and intermediates involved in the synthesis process are described below:
[0895] 1.
##STR00216##
was obtained by the following steps: reacting 5-fluoro-2-nitroanisole (cas:448-19-1, Bidepharm, Shanghai) with 1-methyl-4-(4-piperidyl)piperazine (cas:53617-36-0, Aikonchem, Jiangsu) to obtain
##STR00217##
and then reducing the nitro.
[0896] The following intermediates were obtained in a similar manner:
##STR00218##
[0897] The involved raw materials were: 1-fluoro-5-methoxy-2-methyl-4-nitrobenzene (cas:314298-13-0, Bidepharm, Shanghai), 3,4,5-trifluoronitrobenzene (cas:66684-58-0, Bidepharm, Shanghai), 2,3,4-trifluoronitrobenzene (cas:771-69-7, Bidepharm, Shanghai), 1-methyl-4-(4-piperidyl)piperazine (cas:53617-36-0, Aikonchem, Jiangsu).
[0898] 2.
##STR00219##
was obtained by the following steps: reducing 2-fluoro-4-hydroxyacetophenone (cas: 98619-07-9, Bidepharm, Shanghai) with palladium carbon and hydrogen gas to obtain 3-fluoro-4-ethylphenol, nitrifying the above reduction product to obtain 3-fluoro-4-ethyl-6-nitrophenol, reacting the above nitrification product with iodomethane (cas: 74-88-4, Xiya Reagent, Shandong) to obtain 3-fluoro-4-ethyl-6-nitroanisole, then reacting the above reaction product with N-methylpiperazine (cas: 109-01-3, Energy, Shanghai) to obtain 3-(N-methylpiperazinyl)-4-ethyl-6-nitroanisole, and finally, reducing the nitro.
##STR00220##
was obtained by reducing the nitro in 3-fluoro-4-ethyl-6-nitroanisole.
[0899] The following intermediates were obtained in a similar manner:
##STR00221## ##STR00222##
[0900] The involved raw materials were: 3-N,N-dimethylaminopyrrolidine (cas: 64021-83-6, TCI, Shanghai), 4-dimethylaminopiperidine (cas: 50533-97-6, Accela ChemBio, Shanghai), ethanolamine (cas: 141-43-5, Aladdin, Shanghai), N,N-dimethylethylenediamine (cas: 108-00-9, Bidepharm, Shanghai), N,N,N′-trimethylethylenediamine (cas: 142-25-6, Bidepharm, Shanghai), 2-oxa-6-azaspiro[3.3]heptane (cas: 174-78-7, Bidepharm, Shanghai), 2-methyl-2,6-diazaspiro[3.3]heptane (cas: 1203567-11-6, Bidepharm, Shanghai), 1-methyl-4-(4-piperidyl)piperazine (cas:53617-36-0, Aikonchem, Jiangsu), t-butyl 4-(piperidin-4-yl)piperazinyl-1-carboxylate (cas: 205059-24-1, Bidepharm, Shanghai), 1-(1-methylpiperidin-4-yl)piperazine (cas: 23995-88-2, J&K, Shanghai), 2-methyl-2,7-diazaspiro[3.5]nonane dihydrochloride (cas: 1610028-42-6, Bidepharm, Shanghai), 1-(1-methylazetidin-3-yl)piperazine (cas: 864350-81-2, J&K, Shanghai).
[0901] 3.
##STR00223##
was obtained by the following steps: reacting t-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate (cas:203661-69-2, Bidepharm, Shanghai) with dimethylamine (cas: 124-40-3, Aladdin, Shanghai) to obtain
##STR00224##
after removing t-butoxycarbonyl, reacting the above reaction product with 3-fluoro-4-ethyl-6-nitroanisole in (2) to obtain
##STR00225##
and then reducing the nitro.
[0902] 4.
##STR00226##
was obtained by the following steps: reacting 2,6-dichloro-3-nitropyridine with sodium methoxide (cas: 124-41-4, Energy, Shanghai) to obtain 2-methoxy-3-nitro-6-chloropyridine, reacting the above reaction product with 1-methyl-4-(4-piperidyl)piperazine (cas: 53617-36-0, Aikonchem, Jiangsu) to obtain
##STR00227##
and further reducing the amino.
##STR00228##
was obtained from 2,6-dichloro-3-nitro-5-methylpyridine according to a similar method.
[0903] 5.
##STR00229##
was obtained by the following steps: reacting
##STR00230##
in (3) with liquid bromine (cas: 7726-95-6, Sinopharm, Shanghai) to obtain
##STR00231##
then reacting the above reaction product with pinacol vinylboronate (cas: 75927-49-0, Bidepharm, Shanghai) to obtain
##STR00232##
and further reducing the nitro and the double bond.
[0904] 6.
##STR00233##
was obtained by the following steps: nitrifying 1-bromo-2-fluoro-4-trifluoromethoxybenzene (cas: 168971-68-4, Bidepharm, Shanghai) to obtain 2-trifluoromethoxy-4-fluoro-5-bromonitrobenzene, then reacting the above nitrification product with 1-methyl-4-(4-piperidyl)piperazine (cas: 53617-36-0, Aikonchem, Jiangsu) to obtain
##STR00234##
which was further reacted with pinacol vinylboronate (cas: 75927-49-0, Bidepharm, Shanghai) to obtain
##STR00235##
and further reducing the nitro and the double bond.
[0905] 7.
##STR00236##
was obtained by the following steps: reacting 1-bromo-2-fluoro-4-methoxy-5-nitrobenzene (cas:1352244-77-9, Bidepharm, Shanghai) with 1-methyl-4-(4-piperidyl)piperazine (cas:53617-36-0, Aikonchem, Jiangsu) to obtain
##STR00237##
coupling the above product with isopropenylboronic acid pinacol ester (cas: 126726-62-3, Bidepharm, Shanghai) to obtain
##STR00238##
and further performing a reduction. The following intermediates were obtained in a similar manner:
##STR00239##
[0906] The involved raw materials were: 3-bromo-4-fluoronitrobenzene (cas: 701-45-1, Bidepharm, Shanghai), cyclopropylboronic acid pinacol ester (cas: 126689-01-8, Bidepharm, Shanghai), pinacol vinylboronate (cas: 75927-49-0, Bidepharm, Shanghai).
[0907] 8.
##STR00240##
was obtained by the following steps: nitrifying 2-fluoro-4-methoxybenzaldehyde (cas: 331-64-6) to obtain 2-fluoro-4-methoxy-5-nitrobenzaldehyde, reducing the above nitrification product to obtain 2-fluoro-4-methoxy-5-nitrobenzyl alcohol, further bromating the above reduction product to obtain 2-fluoro-4-methoxy-5-nitrobenzyl bromide, reacting the above bromation product with cyclopropylboronic acid (cas:411235-57-9, Bidepharm, Shanghai) to obtain
##STR00241##
reacting the above reaction product with 1-methyl-4-(4-piperidyl)piperazine (cas: 53617-36-0, Aikonchem, Jiangsu) to obtain
##STR00242##
and finally reducing the nitro.
##STR00243##
was obtained according to a similar method by replacing the cyclopropylboronic acid with phenylboronic acid (cas: 98-80-6, Energy, Shanghai).
[0908] 9.
##STR00244##
was obtained by the following steps: oxidizing 1-bromo-2-methyl-4-methoxy-5-nitrobenzene (cas: 89978-56-3, Jiuding chem, Shanghai) into 2-bromo-4-nitro-5-methoxybenzoic acid, which was suffered from condensation reaction with 1-methyl-4-(4-piperidyl)piperazine (cas: 53617-36-0, Aikonchem, Jiangsu) to obtain
##STR00245##
coupling the above reaction product with potassium vinyltrifluoroborate cas: 13682-77-4, Bidepharm, Shanghai) to obtain
##STR00246##
and performing a reduction.
[0909] 10.
##STR00247##
was obtained by the following steps: reacting m-bromonitrobenzene (cas:585-79-5, Aladdin, Shanghai) with pyridine-4-boronic acid (cas: 1692-15-5, Shuya, Shanghai) to obtain
##STR00248##
further reacting the above reaction product with iodomethane (cas:74-88-4, Xiya Reagent, Shandong) to obtain
##STR00249##
finally, reducing the nitro and the pyridine ring.
was obtained from 4-bromo-2-nitroanisole (cas:33696-00-3, Bidepharm, Shanghai) according to a similar method.
[0910] 11.
##STR00250##
was obtained by the following steps: reacting 6-aminoquinoxaline (cas:6298-37-9, Bidepharm, Shanghai) with iodine monochloride (cas:7790-99-0, Aladdin, Shanghai) to obtain
##STR00251##
and further reacting the above reaction product with dimethylphosphine oxide (cas:7211-39-4, Bidepharm, Shanghai).
[0911] 12.
##STR00252##
was obtained by the following steps: reacting 6-nitroquinoxaline (cas: 6639-87-8, Bidepharm, Shanghai) with hydroxyamine hydrochloride (cas: 5470-11-1, Energy, Shanghai) to obtain 5-amino-6-nitro quinoxaline, then converting the above reaction product to 5-chloro-6-nitroquinoxaline, which was further reacted with N-methyl methanesulfonamide (cas: 1184-85-6, Bidepharm, Shanghai) to obtain
##STR00253##
and finally reducing the nitro. The following intermediates were obtained in a similar manner:
##STR00254##
[0912] The involved raw materials were: methylamine (cas: 74-89-5, Energy, Shanghai), ethylamine (cas: 75-04-7, Aladdin, Shanghai), isopropylamine (cas: 75-31-0, Energy, Shanghai), cyclopropylamine (cas: 765-30-0, Energy, Shanghai), trifluoromethanesulfonyl chloride (cas: 421-83-0, Aladdin, Shanghai), ethylsulfonyl chloride (cas: 594-44-5, Energy, Shanghai), isopropylsulfonyl chloride (cas: 10147-37-2, TCI, Shanghai), cyclopropylsulfonyl chloride (cas: 139631-62-2, Energy, Shanghai), methylsulfamide (cas: 3144-09-0, Bidepharm, Shanghai), isopropylsulfamide (cas: 81363-76-0, Bidepharm, Shanghai).
[0913] 13.
##STR00255##
was obtained by the following steps: reacting 5-chloro-6-nitroquinoxaline in 7) with sodium methylsulfinate (cas:20277-69-4, Bidepharm, Shanghai) to obtain
##STR00256##
reacting the above reaction product with 2,4-dimethoxybenzylamine (cas:20781-20-8, Bidepharm, Shanghai) to obtain
##STR00257##
and further removing 2,4-dimethoxybenzyl.
[0914] 14.
##STR00258##
was obtained by the following steps: reacting 5-chloro-6-nitroquinoxaline in (7) with isopropylmercaptan (cas:75-33-2, Aladdin Shanghai) to obtain
##STR00259##
further oxidizing the above reaction product to obtain
##STR00260##
and finally reducing the nitro.
[0915] 15.
##STR00261##
was obtained by the following steps: reacting 6-amino-5-bromoquinoxaline (cas:50358-63-9, Bidepharm, Shanghai) with di-tert-butyl dicarbonate (cas:24424-99-5, Bidepharm, Shanghai) to obtain
##STR00262##
which was converted into
##STR00263##
by removing t-butoxycarbonyl, reacting the above conversion product with benzylmercaptan (cas:100-53-8, Aladdin, Shanghai) to obtain
##STR00264##
reacting the above reaction product with 1,3-dichloro-5,5-dimethylhydantoin (cas:118-52-5, Bidepharm, Shanghai) to obtain
##STR00265##
which was converted into
##STR00266##
by further reacting with methylamine (cas:74-89-5, Energy, Shanghai), and finally removing t-butoxycarbonyl.
##STR00267##
was obtained according to a similar method by replacing the methylamine with isopropylamine (cas:75-31-0, Energy, Shanghai).
[0916] 16.
##STR00268##
was obtained by the following steps: reacting p-nitrophenylethanol (cas:100-27-6, Bidepharm, Shanghai) with 1,3-dibromo-5,5-dimethylhydantoin (cas:77-48-5, Bidepharm, Shanghai) to obtain 2-bromo-4-nitrophenylethanol, reacting the above reaction product with methylsulfonyl chloride (cas: 124-63-0, Xiya Reagent, Shandong) to obtain 2-bromo-4-nitrophenylethyl mesylate, which was continuously reacted with methylallylamine (cas: 627-37-2, Energy, Shanghai) to obtain
##STR00269##
further converting the above reaction product to
##STR00270##
via a Heck reaction, and finally reducing the nitro and the double bond.
[0917] 17.
##STR00271##
was obtained by the following steps: reacting 2,3,4,5-tetrahydro-1H-benzo[d]azepine (cas:4424-20-8, Bidepharm, Shanghai) with formaldehyde to obtain
##STR00272##
further nitrifying the above reaction product to obtain
##STR00273##
and finally reducing the nitro.
[0918] 18.
##STR00274##
[0919] was obtained by the following steps: reacting 6-fluoro-3,4-dihydro-2H-isoquinolin-1-one (cas:214045-84-8, Bidepharm, Shanghai) with iodomethane (cas: 74-88-4, Xiya Reagent, Shandong) to obtain 2-methyl-6-fluoro-3,4-dihydro-2H-isoquinolin-1-one, reacting the above reaction product with fuming nitric acid (cas: 7697-37-2, Hushi, Shanghai) to obtain 2-methyl-6-fluoro-7-nitro-3,4-dihydro-2H-isoquinolin-1-one, further reducing the carbonyl to obtain 2-methyl-6-fluoro-7-nitro-1,2,3,4-tetrahydroisoquinoline, and finally reducing the nitro.
##STR00275##
was obtained from 6-chloro-3,4-dihydro-2H-isoquinolin-1-one (cas: 22246-02-2, Bidepharm, Shanghai) according to a similar method.
##STR00276##
was obtained from 6-methyl-3,4-dihydro-2H-isoquinolin-1-one (cas:1082041-78-8, Bidepharm, Shanghai) according to a similar method.
##STR00277##
was obtained by the following steps: reducing 3-(trifluoromethoxy)phenylacetonitrile (cas: 108307-56-8, Bidepharm, Shanghai) to obtain 2-(3-trifluoromethoxyphenyl)ethylamine, reacting the above reduction product with ethyl chloroformate (cas: 541-41-3, Xiya Reagent, Shandong) to obtain ethyl 2-(3-trifluoromethoxyphenyl)aminoformate, which was further converted into 6-trifluoromethoxy-3,4-dihydro-2H-isoquinolin-1-one under the action of trifluoromethanesulfonic anhydride (cas: 358-23-6, Energy, Shanghai), and then performing a similar method.
##STR00278##
was obtained from m-trifluoromethylphenylacetonitrile (cas: 2338-76-3, Bidepharm, Shanghai) according to a similar method.
##STR00279##
was obtained by the following steps: reacting 2-methyl-6-fluoro-7-nitro-3,4-dihydro-2H-isoquinolin-1-one with methanol (cas: 67-56-1, Hushi, Shanghai) to obtain 2-methyl-6-methoxy-7-nitro-3,4-dihydro-2H-isoquinolin-1-one, and then performing a similar method.
[0920] 19. 2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amine (cas:14097-40-6, Aikonchem, Jiangsu).
[0921] 20. Pinacol vinylboronate (cas:75927-49-0, Bidepharm, Shanghai).
[0922] 21. Isopropenylboronic acid pinacol ester (cas:126726-62-3, Bidepharm, Shanghai).
[0923] 22. (E)-2-cyclopropyl boronic acid pinacol ester (cas:849061-99-0, Bidepharm, Shanghai).
[0924] 23. (E)-1-ethoxyethene-2-ylboronic acid pinacol ester (cas:1201905-61-4, Bidepharm, Shanghai).
[0925] 24. 2,2-Dimethylethenylboronic acid pinacol ester (cas:126689-00-7, Bidepharm, Shanghai).
[0926] 25. 1-Cyclopentenylboronic acid pinacol ester (cas:287944-10-9, Bidepharm, Shanghai).
[0927] 26. Trans-2-phenylvinylboronic acid pinacol ester (cas:83947-56-2, Bidepharm, Shanghai).
[0928] 27. 2,4-Dichloro-5-bromopyrimidine (cas:36082-50-5, Bidepharm, Shanghai).
[0929] 28. 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (cas:95464-05-4, Bidepharm, Shanghai).
[0930] 29. Sodium hydride (cas:7646-69-7, TCI, Shanghai).
[0931] 30. 3-Aminopyrazole (cas:1820-80-0, Bidepharm, Shanghai).
[0932] 31. 1-Ethyl-3-aminopyrazole (cas:55361-49-4, Bidepharm, Shanghai).
[0933] 32. 1-Isopropyl-3-aminopyrazole (cas:857267-04-0, Bidepharm, Shanghai).
[0934] 33. 1,5-Dimethyl-3-aminopyrazole (cas:35100-92-6, Bidepharm, Shanghai).
[0935] 34.
##STR00280##
was obtained by reacting 3-oxopentanenitrile (cas:33279-01-5, Bidepharm, Shanghai) with methylhydrazine (cas:60-34-4, Xiya Reagent, Shandong).
[0936] 35. 4-aminopyrazole (cas:28466-26-4, Bidepharm, Shanghai).
[0937] 36. 1-methyl-4-aminopyrazole (cas:69843-13-6, Bidepharm, Shanghai).
[0938] 37. 1-ethyl-4-aminopyrazole (cas:876343-24-7, Bidepharm, Shanghai).
[0939] 38. 1-isopropyl-4-aminopyrazole (cas:97421-16-4, Bidepharm, Shanghai).
[0940] 39. 1-ethyl-3-methyl-4-aminopyrazole (cas:947763-34-0, Bidepharm, Shanghai).
[0941] The embodiments of the present invention are described in detail below by way of specific examples, but in any case they cannot be construed as limiting the present invention.
[0942] Synthesis of compound I-1:
##STR00281##
[0943] First step: Compound 1 (442 mg, 2 mmol) was dissolved in DMF (5 mL), and, sodium hydride (60% concentration, dispersed in liquid paraffin wax, 160 mg, 4 mmol) was added thereto in batches at 0° C. After 5 minutes, 2,4-dichloro-5-bromopyrimidine (479 mg, 2.1 mmol) was added and reacted by self-heating for 1 hour, the completion of the reaction was detected by TLC and LCMS. 100 mL of water were added to the reaction mixture to precipitate solids. The solids were filtered and dried under reduced pressure to obtain compound 2 (339 mg), which was directly used for the next step reaction.
[0944] Second step: Compound 2 (41.3 mg, 0.1 mmol), compound 3 (33.2 mg, 0.1 mmol) and methanesulfonic acid (19 μL, 0.3 mmol) in t-BuOH (2 mL) were heated at 100° C. for 4 h, and the completion of the reaction was detected by TLC and LCMS. After cooling, the reaction mixture was concentrated, and purified by silica gel chromatograph (elution with dichloromethane/methanol), to obtain compound 4 (50 mg).
[0945] Third step: Compound 4 (0.042 mmol, 30 mg), pinacol vinylboronate (0.126 mmol, 21 μL), PdCl.sub.2(dppf)CH.sub.2Cl.sub.2 (0.0042 mmol, 3.4 mg), and Na.sub.2CO.sub.3 (0.126 mmol, 13.4 mg) were dispersed in 1,4-dioxane (1 mL) and water (0.5 mL), and after nitrogen gas replacement, the reaction system solution was heated at 100° C. for 4 hours. The completion of the reaction was detected by TLC and LCMS, and the reaction system was diluted with 50 mL of water and then extracted with DCM. The organic phase was concentrated, and purified by silica gel chromatograph (elution with dichloromethane/methanol), and then further purified by preparative HPLC (aqueous solution containing 0.35% trifluoroacetic acid and methanol as mobile phase), to obtain compound I-1 (15.3 g).
[0946] Other such compounds could be synthesized by similar methods.
[0947] In the following table, it lists the specific compounds and their structural characterization data.
TABLE-US-00001 No. Structure .sup.1H NMR and/or MS data I-1
[0948] Biological Activity Assay:
[0949] Growth Inhibitory Activity of Compounds on Cell Lines Stably Transfected with Kinase
[0950] The activity of compounds against various mutants of kinase EGFR was evaluated by their effect of inhibiting growth of BaF.sub.3 cell lines stably transfected with kinase. The specific test method was given as follows:
[0951] 1) Culture medium: DMEM (Dulbecco's modified eagle medium) or RPMI 1640 (containing 10% fetal bovine serum, 100 μg/mL ampicillin, 100 μg/mL streptomycin).
[0952] 2) Reagent: MTS reaction solution (containing 2 mg/mL of MTS [3-(4,5-di methylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazoliu m, inner Salt]; 100 μg/mL of PES (phenazine methosulfate)).
[0953] 3) Compound test: cells were incubated into a 96-well culture plate, the volume of cytosol was 90 μL, and then 10 μL of the compound at each gradient concentration was added. That is, the highest concentration was 10 μM, which was diluted stepwise by ⅓, and 8 concentration points were set in total; 0.1% DMSO (dimethyl sulfoxide) was contained in the system. The cell plate with uniformly mixed compound was cultured in a cell culture incubator (37° C.; 5% 002) for 48 h, then 20 μL of MTS reaction solution was added, uniformly mixed and incubated in the cell culture incubator (37° C.; 5% CO.sub.2) for 1-4 h; OD values at 490 nm were measured by a microplate reader (VARIOSKAN FLASH, Thermo). Two parallels were set in each group of experiments, with 0.1% (a final concentration) DMSO as a negative control, and a culture medium without cells and compounds as a blank control. The cell growth inhibition rate was calculated by the following formula:
Cell growth inhibition rate %=1−(OD.sub.experimental group−OD.sub.blank group)/(OD.sub.negative group−OD.sub.blank group)×100%. [0954] 4) IC.sub.50 calculation: The semi-inhibitory concentration of the compounds acting on cells was calculated using GradPad Prism 5 software according to the measured cell growth inhibition rate.
[0955] The following table lists growth inhibitory activities of compounds on cell lines stably transfected with kinase:
TABLE-US-00002 No. Del L858R Del/T790M L858R/T790M Del/T790M/C797S L858R/T790M/C797S I-1 ++++ ++++ ++++ ++++ ++++ ++++ I-2 ++++ ++++ ++++ ++++ ++++ ++++ I-3 +++ ++++ ++++ +++ ++++ ++++ I-4 ++++ ++++ ++++ ++++ ++++ ++++ I-5 ++++ ++++ ++++ ++++ ++++ ++++ I-6 +++ ++++ ++++ ++++ ++++ ++++ I-7 ++++ ++++ ++++ ++++ ++++ ++++ I-9 ++++ ++++ ++++ ++++ ++++ ++++ I-10 ++++ ++++ ++ +++ +++ +++ I-11 ++++ ++++ +++ +++ +++ +++ I-13 ++++ ++++ +++ +++ +++ +++ I-14 +++ ++++ +++ ++ +++ +++ I-15 ++++ ++++ ++++ ++++ ++++ ++++ I-16 +++ +++ +++ +++ +++ +++ I-17 +++ +++ +++ +++ +++ +++ I-18 +++ ++++ +++ +++ ++++ ++++ I-19 ++++ +++ +++ ++++ ++ +++ I-20 ++ +++ +++ +++ ++ ++ I-21 ++++ ++++ ++++ ++++ ++++ ++++ I-22 +++ +++ +++ ++++ ++ +++ I-23 +++ +++ +++ +++ ++ +++ I-24 +++ ++++ +++ +++ +++ +++ I-25 ++++ ++++ ++++ +++ +++ ++++ II-1 ++++ ++++ ++++ ++++ ++++ ++++ II-2 ++++ ++++ ++++ ++++ ++++ ++++ II-3 ++++ ++++ ++++ ++++ ++++ ++++ II-4 ++++ ++++ ++++ ++++ ++++ ++++ II-5 +++ +++ ++++ ++++ +++ +++ II-6 +++ +++ ++++ +++ ++++ +++ II-7 ++++ ++++ ++++ ++++ ++++ ++++ II-8 +++ +++ +++ +++ +++ +++ II-9 +++ +++ ++++ +++ +++ ++++ II-10 +++ +++ +++ +++ +++ +++ II-11 ++++ +++ ++++ +++ +++ +++ II-12 ++++ ++++ ++++ ++++ ++++ ++++ II-14 ++++ ++++ ++++ ++++ +++ ++++ II-15 ++++ ++++ ++++ ++++ ++++ ++++ 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-49 ++ ++ ++ +++ +++ +++ II-50 ++ ++ +++ +++ +++ +++ II-51 +++ ++ +++ +++ +++ +++ II-52 +++ +++ +++ ++++ ++++ ++++ II-53 +++ +++ +++ +++ ++++ ++++ II-54 ++++ ++++ ++++ +++ ++++ ++++ II-55 +++ +++ +++ +++ +++ +++ 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-76 +++ +++ ++ +++ ++ +++ II-77 ++++ ++++ ++++ ++++ +++ ++++ II-78 ++++ ++++ +++ ++++ +++ ++++ III-1 +++ ++ +++ +++ ++ ++ III-2 ++ ++ +++ +++ ++ +++ III-3 ++ ++ ++ +++ ++ ++ III-4 ++ ++ ++ +++ ++ ++ III-5 ++ ++ ++ +++ ++ ++ III-6 +++ +++ +++ +++ +++ +++ III-9 ++ ++ ++ +++ ++ ++ III-10 ++ ++ ++ +++ ++ ++ III-11 ++ ++ ++ +++ ++ ++ III-12 +++ ++ +++ +++ ++ +++ III-13 +++ ++ +++ +++ ++ ++ III-14 +++ +++ +++ +++ ++ +++ III-16 ++ ++ +++ ++ ++ ++ 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-17 ++ +++ +++ +++ ++ ++ IV-18 +++ +++ +++ +++ ++ ++ Note: “++++” denotes IC.sub.50 ≤ 50 nM; “+++” denotes 50 nM < IC.sub.50 ≤ 500 nM; “++” denotes 500 nM < IC.sub.50 ≤ 2500 nM.
[0956] The other compounds also have good inhibitory activities on the growth of the above cell lines stably transfected with kinase.