Halo-allylamine SSAO/VAP-1 inhibitor and use thereof

1. A compound represented by formula I, a pharmaceutically acceptable salt or a stereoisomer thereof:

wherein, R 1 and R 2 are each independently selected from hydrogen and halogen, and R 1 and R 2 are not hydrogen at the same time;

R 3 and R 4 are each independently selected from hydrogen or C 1-6 alkyl;

R 5 and R 6 are each independently selected from hydrogen or C 1-6 alkyl;

L 1 is a bond, or —CR′R″—, —N—, —O—, —S—, —SO 2 —, S(O), —SONR′—, —SO 2 NR′—, or —NR′CONR′, R′ and R″ are each independently selected from hydrogen or C 1-6 alkyl;

C y1 is the following formula i optionally substituted with a substituent:

wherein, Z 1 , Z 2 , Z 3 and Z 4 are each independently selected from CH or N,

R 8 and R 9 are each independently selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, haloC 1-6 alkyl, haloC 1-6 alkoxyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, 3-8-membered cycloalkyl, aryl, 4-6-membered heterocyclyl, or 5-10-membered heteroaryl, or, optionally R 8 and R 9 form a 3-6 membered cycloalkyl with the atom to which they are attached,

R 10 is selected from hydrogen, hydroxy, cyano, halogen atom, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, haloC 1-6 alkyl, haloC 1-6 alkoxyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, 3-8-membered cycloalkyl, aryl, 4-6-membered heterocyclyl, or 5-10-membered heteroaryl,

R 11 and R 12 are each hydrogen,

m is 0 or 1;

p is 1,

R 7 is each independently selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl,

R a , R b and R c are each independently selected from hydrogen, C 1-6 alkyl optionally substituted with a substituent, C 2-6 alkenyl optionally substituted with a substituent, C 2-6 alkynyl optionally substituted with a substituent, 3-8-membered cycloalkyl optionally substituted with a substituent, aryl optionally substituted with a substituent, 3-12-membered heterocyclyl optionally substituted with a substituent, or 5-10-membered heteroaryl optionally substituted with a substituent, or, optionally R a and R b form a 3-8 membered ring with the atom to which they are attached; C y2 is aryl optionally substituted with a substituent, 3-12-membered heterocyclyl optionally substituted with a substituent, or 5-10-membered heteroaryl optionally substituted with a substituent, n is an integral number of 0-4; said substituents are each independently selected from hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, 3-8-membered cycloalkyl, aryl, 4-6-membered heterocyclyl, or 5-10-membered heteroaryl.

2. The compound according to claim 1 , a pharmaceutically acceptable salt or a stereoisomer thereof, wherein, in the formula I, L 1 is a bond, —CR′R″—, —N—, —O—, or —S—;

R 7 is each independently selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl,

R a , R b and R c are each independently selected from hydrogen, C 1-6 alkyl optionally substituted with a substituent, C 2-6 alkenyl optionally substituted with a substituent, C 2-6 alkynyl optionally substituted with a substituent, 3-8-membered cycloalkyl optionally substituted with a substituent, aryl optionally substituted with a substituent, 4-6-membered heterocyclyl optionally substituted with a substituent or 5-6-membered heteroaryl optionally substituted with a substituent, or, optionally R a and R b form a 4-6-membered ring with the atom to which they are attached; C y2 is phenyl optionally substituted with a substituent, 4-6-membered heterocyclyl optionally substituted with a substituent, or 5-6-membered heteroaryl optionally substituted with a substituent, n is an integral number of 0-3; said substituents are each independently selected from hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, 3-8-membered cycloalkyl, phenyl, 4-6-membered heterocyclyl, or 5-6-membered heteroaryl.

3. The compound according to claim 1 , a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the compound has a structure represented by the following formula II:

wherein, R 1 and R 2 are each independently selected from hydrogen, fluorine, chlorine, or bromine, and R 1 and R 2 are not hydrogen at the same time;

R 3 and R 4 are each independently selected from hydrogen or C 1-6 alkyl;

R 5 and R 6 are each independently selected from hydrogen or C 1-6 alkyl;

L 1 is —CR′R″—, —O— or —S—, R′ and R″ are each independently selected from hydrogen or C 1-6 alkyl;

Z 1 , Z 3 and Z 4 are each independently selected from CH or N;

R 8 and R 9 are each independently selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom or C 1-6 alkyl, or, optionally R 8 and R 9 form a 3-6 membered cycloalkyl with the atom to which they are attached;

R 11 and R 12 are each hydrogen;

R 10 is selected from hydrogen, hydroxy, cyano, halogen atom, or C 1-6 alkyl,

m is 0 or 1; and

R 7 is selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom or C 1-6 alkyl.

4. The compound according to claim 1 , a pharmaceutically acceptable salt or a stereoisomer thereof, wherein, in the formula i

R 8 , R 9 , R 11 and R 12 are each independently selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, haloC 1-6 alkyl, haloC 1-6 alkoxyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, 3-8-membered cycloalkyl, aryl, 4-6-membered heterocyclyl, or 5-10-membered heteroaryl, or, optionally at least one pair of R 8 and R 9 , and R 11 and R 12 form a 3-6 membered cycloalkyl with the atom to which they are attached, or, optionally either R 8 or R 9 , and, either R 11 or R 12 form a 3-6 membered ring with the atoms to which they are attached; or, optionally the atom(s) on C y1 form a 4-7-membered ring together with the atoms in R 6 and L 1 ; or, optionally at least one pair of R 8 and R 9 , and R 11 and R 12 form an oxo group;

R 7 is each independently selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl,

R a , R b and R c are each independently selected from hydrogen, C 1-6 alkyl optionally substituted with a substituent, C 2-6 alkenyl optionally substituted with a substituent, C 2-6 alkynyl optionally substituted with a substituent, 3-8-membered cycloalkyl optionally substituted with a substituent, aryl optionally substituted with a substituent, 4-6-membered heterocyclyl optionally substituted with a substituent or 5-6-membered heteroaryl optionally substituted with a substituent, or, optionally R a and R b form a 4-6-membered ring with the atom to which they are attached; C y2 is phenyl optionally substituted with a substituent, 4-6-membered heterocyclyl optionally substituted with a substituent, or 5-6-membered heteroaryl optionally substituted with a substituent, n is an integral number of 0-3; said substituents are each independently selected from hydroxy, amino, carboxyl, cyano, nitro, halogen atom, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, 3-8-membered cycloalkyl, phenyl, 4-6-membered heterocyclyl, or 5-6-membered heteroaryl,

in the formula i, when at least one of Z 1 , Z 2 , Z 3 and Z 4 is N, and they are not N at the same time, the ring formed by Z 1 , Z 2 , Z 3 and Z 4 is bonded to the L 1 group,

in the formula i, when the ring formed by Z 1 , Z 2 , Z 3 and Z 4 is bonded to the L 1 group, and m is 0, R 10 is selected from hydroxy, cyano, halogen atom, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, haloC 1-6 alkyl, haloC 1-6 alkoxyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, 3-8-membered cycloalkyl, aryl, 4-6-membered heterocyclyl or 5-10-membered heteroaryl,

in the formula i, when the ring formed by Z 1 , Z 2 , Z 3 and Z 4 is bonded to the L 1 group, and m is 1, R 10 is selected from hydroxy, cyano, halogen atom, branched C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 alkoxylC 1-6 alkoxyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, haloC 1-6 alkyl, haloC 1-6 alkoxyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, 3-membered cycloalkyl or 4-membered cycloalkyl.

5. The compound according to claim 1 , a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the compound has a structure represented by the following formula II:

wherein, R 1 and R 2 are each independently selected from hydrogen, fluorine, chlorine, or bromine, and R 1 and R 2 are not hydrogen at the same time;

R 3 and R 4 are each independently selected from hydrogen or C 1-6 alkyl;

R 5 and R 6 are each independently selected from hydrogen or C 1-6 alkyl;

L 1 is a bond, —CR′R″—, —O— and —S—, R′ and R″ are each independently selected from hydrogen or C 1-6 alkyl;

Z 1 , Z 3 and Z 4 are each independently selected from CH or N;

R 8 , R 9 , R 11 and R 12 are each independently selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom or C 1-6 alkyl, or, optionally at least one pair of R 8 and R 9 , and R 11 and R 12 form a 3-6 membered cycloalkyl with the atom to which they are attached; or, optionally either R 8 or R 9 , and, either R 11 or R 12 form a 3-6 membered cycloalkyl with the atoms to which they are attached; or optionally R 8 and R 9 together form an oxo group;

R 10 is selected from hydrogen, hydroxy, cyano, halogen atom, C 1-6 alkyl or 3-6-membered cycloalkyl,

m is 0 or 1;

R 7 is selected from hydrogen, hydroxy, amino, carboxyl, cyano, nitro, halogen atom or C 1-6 alkyl, and

at least one of Z 1 , Z 3 and Z 4 is N, and

wherein, in the compound represented by formula II, in case that m in the left ring carrying a carbonyl is 0, R 10 is selected from hydroxy, cyano, halogen atom, C 1-6 alkyl or 3-6-membered cycloalkyl, preferably R 10 is selected from branched C 1-6 alkyl, 3-membered cycloalkyl or 4-membered cycloalkyl, or

in the compound represented by formula II, in case that m in the left ring carrying a carbonyl is 1, R 10 is selected from hydroxy, cyano, halogen atom, branched C 1-6 alkyl, 3-membered cycloalkyl or 4-membered cycloalkyl, preferably R 10 is selected from branched C 1-6 alkyl, 3-membered cycloalkyl or 4-membered cycloalkyl.

6. The compound according to claim 5 , a pharmaceutically acceptable salt or a stereoisomer thereof:

wherein, R 1 and R 2 are each independently selected from hydrogen, or fluorine, and R 1 and R 2 are not hydrogen at the same time;

R 3 and R 4 are each independently selected from hydrogen or C 1-6 alkyl;

R 5 and R 6 each are hydrogen;

L 1 is —CR′R″— or —O—, R′ and R″ are each independently selected from hydrogen or C 1-6 alkyl;

Z 1 , Z 3 and Z 4 are each independently selected from CH or N;

R 8 , R 9 , R 11 and R 12 are each independently selected from hydrogen or C 1-6 alkyl, or, optionally R 8 or R 9 , with the atom to which they are attached, form cyclopropane, cyclobutane, cyclopentane; or optionally R 8 and R 9 together form an oxo group;

R 10 is selected from branched C 1-6 alkyl, 3-membered cycloalkyl or 4-membered cycloalkyl;

m is 0 or 1; and

R 7 is hydrogen.

7. The compound according to claim 4 , a pharmaceutically acceptable salt or a stereoisomer thereof, wherein, in the formula i, when the ring formed by Z 1 , Z 2 , Z 3 and Z 4 is bonded to the L 1 group, and m is 0, R 10 is selected from hydroxy, cyano, halogen atom, branched C 1-6 alkyl, 3-membered cycloalkyl or 4-membered cycloalkyl.

8. The compound according to claim 4 , a pharmaceutically acceptable salt or a stereoisomer thereof, wherein in the formula i, when the ring formed by Z 1 , Z 2 , Z 3 and Z 4 is bonded to the L 1 group, and m is 1, R 10 is selected from hydroxy, cyano, halogen atom, branched C 1-6 alkyl, 3-membered cycloalkyl or 4-membered cycloalkyl.

9. A compound, a pharmaceutically acceptable salt or a stereoisomer thereof, wherein said compound is selected from:

10. A pharmaceutical composition containing the compound according to claim 1 , a pharmaceutically acceptable salt or a stereoisomer thereof, which optionally contains one or more pharmaceutically acceptable supports.

11. A pharmaceutical composition containing the compound according to claim 9 a pharmaceutically acceptable salt or a stereoisomer thereof, which optionally contains one or more pharmaceutically acceptable supports.