Oxygen-containing heterocyclic compound and use thereof

1 . An oxygen-containing heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof:

wherein:

Ar is C 6-20 aryl, C 6-20 aryl substituted with one or more R 1-1 , “5-12 membered heteroaryl containing 1-4 heteroatoms selected from O, S and N”, or “5-12 membered heteroaryl containing 1-4 heteroatoms selected from O, S and N” substituted with one or more R 1-2 ;

R 1-1 and R 1-2 are independently selected from halogen, hydroxyl and C 1-6 alkyl;

 is a 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N;

R 1 and R 2 are independently selected from hydrogen, deuterium, hydroxyl, C 1-6 alkyl, amino, and —OC 1-6 alkyl;

R 3 and R 4 are C 1-6 alkyl substituted with deuterium, or, R 3 and R 4 together with the atom they are attached form C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted with R 1-3 , 4- to 10-membered heterocycloalkyl containing 1-3 heteroatoms selected from O, S and N, “4- to 10-membered heterocycloalkyl containing 1-3 heteroatoms selected from O, S and N” substituted with R 1-4 , and

R 1-3 and R 1-4 are independently selected from halogen, deuterium, hydroxyl and C 1-6 alkyl.

2 . The oxygen-containing heterocyclic compound represented by Formula I, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 , the oxygen-containing heterocyclic compound represented by Formula I has the structure of Formula II:

wherein represents , or a mixture of and ;

n is 1, 2, 3, 4 or 5; and

Ar and

 are defined as in the Formula I.

3 . The oxygen-containing heterocyclic compound represented by Formula II, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 2 , wherein,

Ar is C 6-20 aryl substituted with one or more R 1-1 , or “5-12 membered heteroaryl containing 1-4 heteroatoms independently selected from O, S and N” substituted with one or more R 1-2 ;

R 1-1 and R 1-2 are independently selected from halogen and C 1-6 alkyl;

is a 5-6 membered heteroaryl containing 1-3 heteroatoms independently selected from O, S and N;

represents or ; and

n is 2 or 3.

4 . The oxygen-containing heterocyclic compound represented by Formula I, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 , the oxygen-containing heterocyclic compound represented by Formula I has the structure of Formula III:

wherein:

Ar and

 are defined as in the Formula I;

represents , or a mixture of and ; and

R 3 and R 4 are C 1-6 alkyl substituted with deuterium.

5 . The oxygen-containing heterocyclic compound represented by Formula III, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 4 , the formula III has the following structure:

wherein, , Ar and

 are defined as in the formula III.

6 . The oxygen-containing heterocyclic compound represented by Formula II, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 2 , wherein,

Ar is C 6-20 aryl substituted with one or more R 1-1 , or “5-12 membered heteroaryl containing 1-4 heteroatoms independently selected from O, S and N” substituted with one or more R 1-2 ;

R 1-1 and R 1-2 are independently selected from halogen and C 1-6 alkyl;

is 5-6 membered heteroaryl containing 1-3 heteroatoms independently selected from O, S and N;

represents or ; and

n is 2 or 3.

7 . The oxygen-containing heterocyclic compound represented by Formula I, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 , wherein,

when Ar is C 6-20 aryl, or C 6-20 aryl substituted with one or more R 1-1 , the C 6-20 aryl and the C 6-20 aryl in the C 6-20 aryl substituted with one or more R 1-1 are C 6-10 aryl; the C 6-10 aryl is phenyl or naphthyl;

and/or, when Ar is “5-12 membered heteroaryl containing 1-4 heteroatoms independently selected from O, S and N”, or “5-12 membered heteroaryl containing 1-4 heteroatoms independently selected from O, S and N” substituted with one or more R 1-2 , the “5-12 membered heteroaryl containing 1-4 heteroatoms independently selected from O, S and N” and “5-12 membered heteroaryl containing 1-4 heteroatoms independently selected from O, S and N” in the “5-12 membered heteroaryl containing 1-4 heteroatoms independently selected from O, S and N” substituted with one or more R 1-2 are “5 membered heteroaryl containing 2 heteroatoms selected from N”;

and/or, when

 is a 5-6 membered heteroaryl containing 1-3 heteroatoms independently selected from O and N, the

 is a 5 membered heteroaryl containing 3 heteroatoms independently selected from O and N;

and/or, when R 1-1 and R 1-2 are independently selected from halogen, then the halogen is —F, —Cl, —Br or —I;

and/or, when R 1-1 and R 1-2 are independently selected from C 1-6 alkyl, then the C 1-6 alkyl is C 1-4 alkyl, or may be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, or may be methyl;

and/or, when R 3 and R 4 together with the atom they are attached form C 3-8 cycloalkyl, then the C 3-8 cycloalkyl is C 3 cycloalkyl, C 4 cycloalkyl, C 5 cycloalkyl, C 6 cycloalkyl, C 7 cycloalkyl, or C 5 cycloalkyl;

and/or, when R 3 and R 4 are C 1-6 alkyl substituted with deuterium, then the C 1-6 alkyl is C 1-4 alkyl, or may be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, or may be methyl;

and/or, when R 3 and R 4 are C 1-6 alkyl substituted with deuterium, then the C 1-6 alkyl substituted with deuterium is —CD 3 .

8 . The oxygen-containing heterocyclic compound represented by Formula I, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 , wherein,

Ar is

9 . The oxygen-containing heterocyclic compound represented by Formula I, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 , wherein,

10 . The compound, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, solvate thereof, solvate of the pharmaceutically acceptable salt thereof or crystal form thereof according to claim 1 wherein R 1 is hydrogen; R 2 is selected from hydrogen, deuterium, and hydroxyl; R 3 and R 4 are C 1-6 alkyl substituted with deuterium, or, R 3 and R 4 together with the atom to which they are attached form C 3-6 cycloalkyl;

is oxadiazolyl; and Ar is chosen from phenyl substituted with one or more R 1-1 and pyrazolyl substituted with one or more R 1-2 .

11 . The oxygen-containing heterocyclic compound represented by Formula I, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 , wherein, the oxygen-containing heterocyclic compound of Formula I have any one of the following structures:

12 . A pharmaceutical composition comprising a substance A and a pharmaceutically acceptable excipient, wherein the substance A is a therapeutically effective amount of the oxygen-containing heterocyclic compound represented by Formula I, the pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 .

13 . A method for inhibiting the interaction of homeodomain interacting protein kinase 2 with Smad3, said method comprising combining HIPK2 with a substance A, wherein the substance A is a therapeutically effective amount of the oxygen-containing heterocyclic compound of Formula I, a pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 .

14 . A method for inhibiting Smad3 activation, wherein the method comprising bringing Smad3 into contact with a substance A, wherein the substance A is a therapeutically effective amount of the oxygen-containing heterocyclic compound of Formula I, a pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 .

15 . A method for treating a fibrotic disease comprising administrating a substance A to a subject suffering from a fibrotic disease, wherein the substance A is a therapeutically effective amount of the oxygen-containing heterocyclic compound of Formula I, a pharmaceutically acceptable salt thereof, deuterated derivative thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof or a crystal form thereof according to claim 1 , wherein the disease is renal fibrosis, cardiac fibrosis, hepatic fibrosis, or pulmonary fibrosis.