# US 11,440,909 B2 · 10H-phenothiazine ferroptosis inhibitor as well as the preparative method and the use thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,440,909 B2
- Document ID: US11440909B2
- Status: Granted
- Kind: B2
- Application number: 17/078,802
- Filed: 2020-10-23
- Published: 2021-02-11
- Granted: 2022-09-13
- Earliest claimed: 2018-04-27
- Assignees: Chengdu Henghao Investment Co. Limited
- Applicants: Chengdu Henghao Investment Co. Limited
- Inventors: Shengyong Yang; Linli Li
- Web page: https://patentgrep.com/patent/US11440909B2

## CPC

- C07D 417/12: linked by a chain containing hetero atoms as chain links
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C07D 279/20: with hydrogen atoms directly attached to the ring nitrogen atom
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 417/10: linked by a carbon chain containing aromatic rings
- C07D 417/14: containing three or more hetero rings
- C07D 451/06: Oxygen atoms
- C07D 471/08: Bridged systems
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

10H-phenothiazine derivatives capable of inhibiting ferroptosis has structural formula (I). The derivatives, pharmaceutically acceptable salts thereof, crystal forms thereof, or solvates thereof exhibit inhibitory effect on ferroptosis, and therapeutic effect on a rat model of focal cerebral ischemia and thus can be used as a main active ingredient in the preparation of ferroptosis inhibitors. The compounds and the inhibitors prepared by the compounds have good medicinal potential and are expected to be used as drug candidates for the treatment of stroke.

## Claims

### Claim 1

A compound of formula I, or a pharmaceutically acceptable salt, or a solvate thereof:
wherein,
when the dotted line is a bond,
R1 is selected from 3-10 membered saturated cycloalkyl, 3-10 membered unsaturated cycloalkyl, 3-10 membered saturated heterocyclic group, and 3-10 membered unsaturated heterocyclic group, all of which are substituted by m R2, with m being an integer of 0-5;
R2 is selected from substituted or unsubstituted C1-C8 linear or branched alkyl, substituted or unsubstituted C1-C8 alkoxy, substituted or unsubstituted 3-10 membered saturated cycloalkyl, substituted or unsubstituted 3-10 membered saturated heterocyclic group, substituted or unsubstituted 3-10 membered unsaturated cycloalkyl, carbazolyl, amino, hydroxyl, nitro, cyano, halogen, —C(O)OR51, —N(H)C(O)R51, —C(O)R51, —S(O)(O)R51, and —C(O)N(H)R51;
R51 is selected from H, C1-C8 linear or branched alkyl, amino, substituted or unsubstituted 3-10 membered unsaturated cycloalkyl, substituted or unsubstituted 3-10 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently selected from H, substituted or unsubstituted 5-10 membered saturated heterocyclic groups, substituted or unsubstituted C1-C8 linear or branched alkyl, and substituted or unsubstituted 3-8 membered saturated cycloalkyl;
wherein, in R1, R2, R51, R52, and R53, a substituent of the alkyl is selected from halogen and substituted or unsubstituted 4-10 membered saturated heterocyclic group;
a substituent of the alkoxyl is selected from halogen and 3-10 membered unsaturated cycloalkyl;
a substituent of the saturated cycloalkyl is C1-C8 alkyl;
a substituent of the unsaturated cycloalkyl is C1-C8 alkyl;
a substituent of the saturated heterocyclic group is C1-C8 alkyl;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N, O, and S;
the saturated heterocyclic group comprises one or two heteroatoms selected from N, O, and S; and
wherein, when the dotted line is none,
R1 is selected from 3-10 membered unsaturated cycloalkyl, benzo(3-8 membered saturated)heterocyclic group, benzo(3-8 membered unsaturated)heterocyclic group, anthryl, 3-10 membered unsaturated heterocyclic group, and 3-10 membered saturated cycloalkyl, all of which are substituted by n R3, n being an integer of 0-5, or R1 is —S(O)(O)R1′, with the proviso that n is 1, 2, 3, 4, or 5 when R1 is a 3-10 membered unsaturated cycloalkyl;
R3 is selected from halogen, cyano, hydroxyl, amino, nitro, substituted or unsubstituted 3-10 membered unsaturated cycloalkyl, phenoxyl, substituted or unsubstituted 3-10 membered saturated heterocyclic group, substituted C1-C8 alkyl, substituted or unsubstituted C1-C8 alkoxy, —C(O)OR51, —N(H)C(O)R51, and —NR22R53;
R1′ is selected from 3-10 membered saturated heterocyclic group, 3-10 membered saturated cycloalkyl, 3-10 membered unsaturated cycloalkyl, and 3-10 membered unsaturated heterocyclic group, all of which are substituted by p R4, with p being an integer of 0-5;
R4 is selected from hydroxyl, substituted or unsubstituted C1-C8 alkyl, —C(O)R51, —N(H)C(O)OR51, —S(O)(O)R51,_—C(O)OR51, substituted or unsubstituted 3-10 membered unsaturated heterocyclic group, substituted or unsubstituted 3-10 membered saturated heterocyclic group, and substituted or unsubstituted 3-10 membered unsaturated cycloalkyl;
R51 is selected from C1-C10 alkyl, amino, 3-8 membered saturated heterocyclic group, and benzo(3-8 membered saturated)heterocyclic group;
R52 and R53 are each independently selected from 3-10 membered unsaturated cycloalkyl, and C1-C8 linear or branched alkyl;
wherein, in R1, R2, R51, R52, or R53, a substituent of the alkyl is selected from halogen, benzo(5-10 membered saturated)heterocyclic group, substituted or unsubstituted 3-10 membered unsaturated cycloalkyl, 5-10 membered saturated heterocyclic group, hydroxyl, —N(H)C(O)OR51, —C(O)R51, and —NR52R53;
a substituent of the alkoxyl is selected from 3-10 membered unsaturated cycloalkyl and halogen;
a substituent of the unsaturated cycloalkyl is selected from halogen, C1-C6 alkoxyl, cyano, nitro, and substituted or unsubstituted C1-C8 alkyl;
a substituent of the saturated heterocyclic group is C1-C8 alkyl;
a substituent of the unsaturated heterocyclic group is C1-C8 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O, N, and S; and
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N, O, and S.

### Claim 2 (depends on 1)

The compound according to claim 1, or the pharmaceutically acceptable salt, or the solvate thereof, wherein:
when the dotted line is a bond,
R1 is selected from 3-8 membered unsaturated cycloalkyl, and 3-8 membered unsaturated heterocyclic group, all of which are substituted by m R2 and m being an integer of 0-4;
R2 is selected from substituted or unsubstituted C1-C6 linear or branched alkyl, substituted or unsubstituted C1-C6 alkoxy, 3-8 membered saturated cycloalkyl, substituted or unsubstituted 3-8 membered saturated heterocyclic group, 3-8 membered unsaturated cycloalkyl, carbazolyl, amino, hydroxyl, nitro, cyano, halogen, —C(O)OR51, —N(H)C(O)R51, —C(O)R51, —S(O)O)R51, and —C(O)N(H)R51;
R51 is selected from H, C1-C4 linear or branched alkyl, amino, substituted or unsubstituted 3-8 membered unsaturated cycloalkyl, substituted or unsubstituted 5-8 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently selected from H, substituted or unsubstituted 5-8 membered saturated heterocyclic group, substituted or unsubstituted C1-C6 linear or branched alkyl, and 3-6 membered saturated cycloalkyl;
wherein, in R1, R2, R51, R52, or R53, the substituent of the alkyl is selected from halogen and substituted or unsubstituted 5-8 membered saturated heterocyclic group;
the substituent of the alkoxyl is selected from halogen and 3-8 membered unsaturated cycloalkyl;
the substituent of the unsaturated cycloalkyl is C1-C4 alkyl;
the substituent of the saturated heterocyclic group is C1-C4 alkyl;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O;
the saturated heterocyclic group comprises one or two heteroatoms selected from N and O;
where, when the dotted line is none,
R1 is selected from 3-8 membered unsaturated cycloalkyl, benzo(5-8 membered saturated)heterocyclic group, benzo(5-8 membered unsaturated)heterocyclic group, anthryl, 3-8 membered unsaturated heterocyclic group, and 3-8 membered saturated cycloalkyl, all of which are substituted by n R3, and S(O)(O)R1′, with n being an integer of 1-4;
R3 is selected halogen, cyano, hydroxyl, amino, nitro, 3-8 membered unsaturated cycloalkyl, phenoxyl, substituted 5-8 membered saturated heterocyclic group, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, —C(O)OR51, —N(H)C(O)R51, and —NR52R53;
R1′ is 3-8 membered saturated heterocyclic group substituted by p R4, with p being an integer of 0-4;
R4 is selected from hydroxyl, substituted or unsubstituted C1-C6 alkyl, —C(O)R51, —N(H)C(O)OR51, —S(O)(O)R51, —C(O)OR51, 3-8 membered unsaturated heterocyclic group, 3-8 membered saturated heterocyclic group, and substituted or unsubstituted 3-8 membered unsaturated cycloalkyl;
R51 is selected from C1-C8 alkyl, amino, 5-8 membered saturated heterocyclic group, and benzo(5-8 membered saturated)heterocyclic group;
R52 and R53 are each independently selected from 3-8 membered unsaturated cycloalkyl and C1-C4 alkyl;
wherein, in R1, R3, R4, R51, R52, or R53, the substituent of the alkyl is selected from halogen, benzo(5-8 membered saturated)heterocyclic group, substituted or unsubstituted 3-8 membered unsaturated cycloalkyl, 5-10 membered saturated heterocyclic group, hydroxyl, —N(H)C(O)OR51, —C(O)R51, and —NR52R53;
the substituent of the alkoxyl is selected from 3-8 membered unsaturated cycloalkyl and halogen;
wherein the substituent of the unsaturated cycloalkyl is selected from halogen, C1-C4 alkoxyl, cyano, nitro, and substituted or unsubstituted C1-C4 alkyl;
the substituent of the saturated heterocyclic group is C1-C4 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O, N, and S;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O.

### Claim 3 (depends on 2)

The compound according to claim 2, or the pharmaceutically acceptable salt, or the solvate thereof, wherein said compound has a structure of formula II:
wherein, ring A is selected from aryl substituted by m R2 and heteroaryl substituted by m R2; said heteroaryl comprises one or two N, and
m is an integer of 0-4;
R2 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, 6-8 membered saturated cycloalkyl, substituted or unsubstituted 6-7 membered saturated heterocyclic group, carbazolyl, amino, hydroxyl, nitro, aryl, cyano, halogen, —C(O)OR51, —N(H)C(O)R51, —C(O)R51, —S(O)(O)R51, and —C(O)N(H)R51;
R51 is selected from H, C1-C2 alkyl, amino, substituted or unsubstituted aryl, substituted or unsubstituted 5-6 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently selected from H, substituted or unsubstituted 6-8 membered saturated heterocyclic group, substituted or unsubstituted C1-C4 linear or branched alkyl, and 4-5 membered saturated cycloalkyl;
wherein, in R2, R51, R52, or R53, the substituent of the alkyl is selected from halogen and substituted or unsubstituted 6-8 membered saturated heterocyclic group;
the substituent of the alkoxyl is selected from halogen and aryl;
the substituent of the aryl is substituted C1-C3 alkyl;
the substituent of the saturated heterocyclic group is C1-C3 alkyl;
said heterocyclic group comprises one or two heteroatoms selected from N and O,
or, said compound has a structure of formula III:
wherein, ring B is selected from aryl, benzo(5-6 membered saturated)heterocyclic group, benzo(5 membered unsaturated)heterocyclic group, anthryl, 6-8 membered unsaturated heterocyclic group, and 6-8 membered saturated cycloalkyl, all of which are substituted by n R3, with n being an integer of 1-3;
R3 is selected from H, halogen, cyano, hydroxyl, amino, nitro, aryl, phenoxy, substituted 6-8 membered saturated heterocyclic group, substituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, —C(O)OR51, —N(H)C(O)R51, and —NR52R53;
R51 is selected from C1-C4 alkyl;
R52 and R53 are each independently selected from aryl;
wherein, in R3 or R51, the substituent of the alkyl is halogen;
the substituent of the alkoxyl is selected from aryl and halogen;
the substituent of the saturated heterocyclic group is C1-C2 alkyl;
the saturated heterocyclic group comprises one or two heteratoms selected from N and O;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O;
or, said compound has a structure of formula IV:
wherein, ring C is a 5-8 membered saturated heterocyclic group substituted by p R4;
p is an integer of 0-4;
R4 is selected from H, hydroxyl, substituted or unsubstituted C1-C4 alkyl, —C(O)R51, —N(H)C(O)OR51, —S(O)(O)R51, —C(O)OR51, 6-8 membered unsaturated heterocyclic group, 6-8 membered saturated heterocyclic group, and substituted or unsubstituted aryl;
R51 is selected from C1-C4 alkyl, amino, 5 membered saturated heterocyclic group, and benzo(6 membered saturated)heterocyclic group;
wherein, in R4 or R51, the substituent of the alkyl is selected from halogen, benzo(5 membered saturated)heterocyclic group, substituted or unsubstituted aryl, 6 membered saturated heterocyclic group, hydroxyl, —N(H)C(O)OR51, —C(O)R51, and —NR52R53;
the substituent of the aryl is selected from halogen, C1 alkoxyl, cyano, nitro, and substituted or unsubstituted C1 alkyl;
R52 and R53 are each C1 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O, N, and S; and
the unsaturated heterocyclic group comprises one or two N.

### Claim 4 (depends on 3)

The compound according to claim 3, or the pharmaceutically acceptable salt, or the solvate thereof, wherein said compound has a structure of formula IIA:
wherein, R21, R22, R23, and R24 are each independently selected from H, —C(O)OR51, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, —N(H)C(O)R51, 6 membered saturated cycloalkyl, —C(O)R51, 6-membered saturated heterocyclic group, carbazolyl, amino, hydroxyl, nitro, —S(OXO)R51, aryl, cyano, halogen, and —C(O)N(H)R51;
R51 is selected from H, C1-C2 alkyl, amino, substituted or unsubstituted aryl, substituted or unsubstituted 5-6 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently of selected from H, substituted or unsubstituted 6 membered saturated heterocyclic group, substituted or unsubstituted C1-C4 linear or branched chain alkyl, and 4 membered cycloalkyl;
wherein, in R21, R22, R23, R24, R51, R52, and R53, the substituent of the alkyl is selected from halogen and substituted or unsubstituted 6 membered saturated heterocyclic group;
the substituent of the alkoxyl is selected from halogen and aryl;
the substituent of the aryl is substituted C1 alkyl;
the substituent of the saturated heterocyclic group is C1 alkyl; said saturated heterocyclic group comprises one or two heteroatoms selected from N and O;
or, said compound has a structure of formula IIB:
wherein, R25 is selected from substituted or unsubstituted 6-7 membered saturated heterocyclic group and
the substituent of the saturated heterocyclic group is C1 alkyl;
said heterocyclic group comprises one or two heteroatoms selected from N and O;
or, said compound has a structure of formula IIC:
wherein, R26 is selected from —N(H)C(O)R51, amino, and 6 membered saturated heterocyclic group;
said saturated heterocyclic group comprises two heteroatoms selected from N and O; and
R51 is C1 alkyl;
or, said compound has a structure of formula IIIA:
wherein, R31, R32, and R33 are each independently selected from H, halogen, cyano, hydroxyl, amino, substituted or unsubstituted C1-C3 alkoxy, —C(O)OR51, —N(H)C(O)R51, aryl, phenoxy, —NR52R53, substituted 6 membered saturated heterocyclic group, and nitro, with the proviso that all of R31, R32, and R3 are not simultaneously H;
R51 is C1-C4 alkyl;
wherein, in R31, R32, and R33, the substituent of the alkyl is halogen;
the substituent of the alkoxyl is selected from aryl and halogen;
the substituent of the saturated heterocyclic group is C1 alkyl;
the saturated heterocyclic group comprise two N;
R52 and R53 are each independently aryl;
or, said compound has a structure of formula IIIB:
wherein, ring B is selected from benzo(5-6 membered saturated)heterocyclic group, benzo(5 membered unsaturated)heterocyclic group, anthryl, and substituted 6 membered unsaturated heterocyclic group or 6 membered saturated cycloalkyl;
the substituent of the unsaturated heterocyclic group is selected from cyano, C1 alkyl, and C2 alkoxyl;
the saturated heterocyclic group comprises one or two O;
the unsaturated heterocyclic group comprises one heteroatom selected from O and N;
or, said compound has a structure of formula IVA:
wherein, R41, R42, R43, and R44 are each independently selected from H, hydroxyl, —N(H)C(O)OR51, and substituted or unsubstituted C1 alkyl;
R51 is C4 alkyl;
the substituent of the alkyl is —N(H)C(O)OR51;
or, said compound has a structure of formula IVB:
wherein, R41′, R42′, R43′, and R44′ are each independently selected from H and hydroxyl;
or, said compound has a structure of formula IVC:
wherein, R41″, R42″, R43″, and R44″ are each independently selected from H, C1 alkyl, —C(O)R51;
R51 is C1 alkyl;
or, said compound has a structure of formula IVD:
wherein, R45, R46, R47, and R48 are each independently selected from H, substituted or unsubstituted C1-C4 alkyl, —C(O)R51, —S(O)(O)R51, 6 membered unsaturated heterocyclic group, —C(O)OR51, and substituted or unsubstituted aryl;
R51 is selected from 5 membered saturated heterocyclic group, C1-C4 alkyl, and benzo(6 membered saturated)heterocyclic group;
R52 and R53 are each independently C1 alkyl;
the substituent of the alkyl is selected from halogen, benzo(5 membered saturated)heterocyclic group, —C(O)R51, —NR52R53, substituted or unsubstituted aryl, 6 membered saturated heterocyclic group, and hydroxyl;
the substituent of the aryl is selected from C1 alkoxyl, halogen, cyano, nitro, and substituted or unsubstituted C1 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O and N;
the unsaturated heterocyclic group comprises one or two N;
or, said compound has a structure of formula IVE:
wherein, R45′, R46′, R47′, and R48′ are each independently selected from H and C1 alkyl;
or, said compound has a structure of formula IVF:
wherein, R45″, R46″, R47″, and R48″ are each independently selected from H and C1 alkyl;
or, said compound has a structure of formula IVG:
wherein, R45′″, R46′″, R47′″, and R48′″ are each independently selected from H, hydroxyl, —C(O)OR51, —N(H)C(O)OR51, substituted aryl, substituted or unsubstituted C1 alkyl, 6 membered saturated heterocyclic group, and —C(O)R51;
R51 is selected from C2-C4 alkyl and amino;
the substituent of the aryl is halogen;
the substituent of the alkyl is selected from —N(H)C(O)OR51 and hydroxyl;
the saturated heterocyclic group comprises one N.

### Claim 5 (depends on 1)

The compound according to claim 1, or the pharmaceutically acceptable salt, or the solvate thereof, wherein said compound is selected from:

### Claim 6 (depends on 1)

A preparative method for the compound, or the pharmaceutically acceptable salt, or the solvate thereof according to claim 1, wherein the method includes the following steps:
(1) 2-Acetylphenothiazine and 4-methylbenzenesulfonyl hydrazide are used as starting materials, and dissolved in MeOH, to which is then added the catalyst HOAc; the mixture is heated to 60° C. for reaction, and the progress of the reaction is monitored. After completion of the reaction, the reaction is cooled to room temperature, filtered under reduced pressure, and the filtrate is rinsed to be colorless, then dried in vacuo to provide intermediate 1;
(2) Intermediate I, starting material A, and anhydrous K2CO3 are dissolved in 1,4-dioxane, and then reacted at 110° C.; the progress of the reaction is monitored. And after completion of the reaction, the mixture is cooled to room temperature and concentrated under reduced pressure to remove 1, 4-dioxane; the residue is extracted, and the organic layer is concentrated and then separated by column chromatography to obtain the target product;
or, the method includes the following steps:
(1) 2-Acetylphenothiazine and 4-methylbenzenesulfonyl hydrazide are used as starting materials, that are dissolved in MeOH, to which is then added the catalyst HOAc; the mixture is heated to 60° C. for reaction, and the progress of the reaction is monitored. After completion of the reaction, the reaction is
cooled to room temperature, filtered under reduced pressure, and the filtrate is rinsed to be colorless, then dried in vacuo to obtain intermediate I;
(2) Intermediate I, starting material A, tris(dibenzylidene-BASE acetone)dipalladium, 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl and anhydrous t-BuOLi are dissolved in 1,4-dioxane, to which argon is purged and exchanged for 3 times; the resultant mixture is heated to 70° C. for reaction, and the reaction is monitored by TLC. After about 4 h, the reaction is completed, cooled to room temperature, filtered, concentrated under reduced pressure, and the residue is extracted; the organic layer is concentrated and separated by column chromatography to provide the target compound;
or, the method includes the following steps:
(1) 2-Acetylphenothiazine and 4-methylbenzenesulfonyl hydrazide are used as starting materials, that are dissolved in MeOH, to which is then added the catalyst HOAc; the mixture is heated to 60° C. for reaction, and the progress of the reaction is monitored. After completion of the reaction, the reactions are cooled to room temperature, filtered under reduced pressure, and the filtrate is rinsed to be colorless, then dried in vacuo to provide intermediate I;
(2) Intermediate I, starting material A, and DABSO are dissolved in DMSO, to which argon is purged and exchanged for 3 times; the resultant mixture is heated to 100° C. for reaction, and the reaction is monitored. After about 12 h, the reaction is completed, cooled to room temperature, filtered, concentrated under reduced pressure, and the residue is extracted; the organic layer is concentrated and separated by column chromatography to provide the target compound.

### Claim 7 (depends on 6)

The preparative method according to claim 6, wherein in said step (2), starting material A is selected from

### Claim 8 (depends on 6)

The preparative method according to claim 6, wherein in said step (1), during the rinsing process after completion of the reaction, MeOH and ethyl ether are used to wash; and/or in the step (2), during the extraction process after completion of the reaction, the extraction is carried out with saturated NaHCO3/DCM; and/or, the reaction process is detected all by TLC.

### Claim 9 (depends on 1)

A method for inhibiting cell ferroptosis, comprising: administering a pharmaceutically acceptable amount of the compound, or the pharmaceutically acceptable salt, or the solvate thereof according to claim 1 to a subject in need thereof.

### Claim 10 (depends on 1, 9)

The method according to claim 9, wherein, in the compound according to claim 1, when the dotted line is a bond,
R1 is selected from 3-8 membered unsaturated cycloalkyl, and 3-8 membered unsaturated heterocyclic group, all of which are substituted by m R2;
m is an integer of 0-4;
R2 is selected from substituted or unsubstituted C1-C6 linear or branched chain alkyl, substituted or unsubstituted C1-C6 alkoxy, 3-8 membered saturated cycloalkyl, substituted or unsubstituted 3-8 membered saturated heterocyclic group, 3-8 membered unsaturated cycloalkyl, carbazolyl, amino, hydroxyl, nitro, cyano, halogen, —C(O)OR51, —N(H)C(O)R51, —C(O)R51, —S(OXO)R51, and —C(O)N(H)R51;
R51 is selected from H, C1-C4 alkyl, amino, substituted or unsubstituted 3-8 membered unsaturated cycloalkyl, substituted or unsubstituted 5-8 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently selected from H, substituted or unsubstituted 5-8 membered saturated heterocyclic group, substituted or unsubstituted C1-C6 linear or branched chain alkyl, and 3-6 membered saturated cycloalkyl;
the substituent of the alkyl is selected from halogen and substituted or unsubstituted 5-8 membered saturated heterocyclic group;
the substituent of the alkoxyl is selected from halogen and 3-8 membered unsaturated cycloalkyl;
the substituent of the unsaturated cycloalkyl is C1-C4 alkyl;
the substituent of the saturated heterocyclic group is C1-C4 alkyl;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O;
the saturated heterocyclic group comprises one or two heteroatoms selected from N and O;
when the dotted line is none,
R1 is selected from 3-8 membered unsaturated cycloalkyl, benzo(5-8 membered saturated)heterocyclic group, benzo(5-8 membered unsaturated)heterocyclic group, anthryl, 3-8 membered unsaturated heterocyclic group, 3-8 membered saturated cycloalkyl, all of which are substituted by n R3, and S(O)(O)R1′;
n is an integer of 1-4;
R3 is selected from halogen, cyano, hydroxyl, amino, nitro, 3-8 membered unsaturated cycloalkyl, phenoxyl, substituted 5-8 membered saturated heterocyclic group, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, —C(O)OR51, —N(H)C(O)R51, and —NR52R53;
R1′ is selected from 3-8 membered saturated heterocyclic group substituted by p R4;
p is an integer of 0-4;
R4 is selected from hydroxyl, substituted or unsubstituted C1-C6 alkyl, —C(O)R51, —N(H)C(O)OR51, —S(O)(O)R51, —C(O)OR51, 3-8 membered unsaturated heterocyclic group, 3-8 membered saturated heterocyclic group, and substituted or unsubstituted 3-8 membered unsaturated cycloalkyl;
R51 is selected from C1-C8 alkyl, amino, 5-8 membered saturated heterocyclic group, and benzo(5-8 membered saturated)heterocyclic group;
R52 and R53 are each independently selected from 3-8 membered unsaturated cycloalkyl and C1-C4 alkyl;
The substituent of the alkyl is selected from halogen, benzo(5-8 membered saturated)heterocyclic group, substituted or unsubstituted 3-8 membered unsaturated cycloalkyl, 5-10 membered saturated heterocyclic group, hydroxyl, —N(H)C(O)OR51, —C(O)R51, and —NR52R53;
the substituent of the alkoxyl is selected from 3-8 membered unsaturated cycloalkyl and halogen;
the substituent of the unsaturated cycloalkyl is selected from halogen, C1-C4 alkoxyl, cyano, nitro, and substituted or unsubstituted C1-C4 alkyl;
the substituent of the saturated heterocyclic group is C1-C4 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O, N, and S;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O.

### Claim 11 (depends on 1, 9)

The method according to claim 9, wherein the compound according to claim 1 has a structure of formula II:
wherein, ring A is selected from aryl substituted by m R2 and heteroaryl substituted by m R2; said heteroaryl comprises one or two N, and
m is an integer of 0-4;
R2 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, 6-8 membered saturated cycloalkyl, substituted or unsubstituted 6-7 membered saturated heterocyclic group, carbazolyl, amino, hydroxyl, nitro, aryl, cyano, halogen, —C(O)OR51, —N(H)C(O)R51, —C(O)R51, —S(O)(O)R51, and —C(O)N(H)R51;
R51 is selected from H, C1-C2 alkyl, amino, substituted or unsubstituted aryl, substituted or unsubstituted 5-6 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently selected from H, substituted or unsubstituted 6-8 membered saturated heterocyclic group, substituted or unsubstituted C1-C4 linear or branched chain alkyl, and 4-5 membered saturated cycloalkyl;
the substituent of the alkyl is selected from halogen and substituted or unsubstituted 6-8 membered saturated heterocyclic group;
the substituent of the alkoxyl is selected from halogen and aryl;
the substituent of the aryl is substituted C1-C3 alkyl;
the substituent of the saturated heterocyclic group is C1-C3 alkyl; said heterocyclic group comprises one or more heteroatoms selected from N and O,
Or, said compound has a structure of formula Ill:
wherein, ring B is selected from aryl, benzo(5-6 membered saturated)heterocyclic group, benzo(5 membered unsaturated)heterocyclic group, anthryl, 6-8 membered unsaturated heterocyclic group, and 6-8 membered saturated cycloalkyl, all of which are substituted by n R3, n is an integer of 1-3;
R3 is selected from H, halogen, cyano, hydroxyl, amino, nitro, aryl, phenoxy, substituted 6-8 membered saturated heterocyclic group, substituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, —C(O)OR51, —N(H)C(O)R51, and —NR52R53;
R51 is C1-C4 alkyl;
R52 and R53 are each independently aryl;
the substituent of the alkyl is halogen;
the substituent of the alkoxyl is selected from aryl and halogen;
the substituent of the saturated heterocyclic group is C1-C2 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from N and O;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O;
or, said compound has a structure of formula IV:
wherein, ring C is a 5-8 membered saturated heterocyclic group substituted by p R4;
p is an integer of 0-4;
R4 is selected from H, hydroxyl, substituted or unsubstituted C1-C4 alkyl, —C(O)R51, —N(H)C(O)OR51, —S(O)(O)R51, —C(O)OR51, 6-8 membered unsaturated heterocyclic group, 6-8 membered saturated heterocyclic group, and substituted or unsubstituted aryl;
R51 is selected from C1-C4 alkyl, amino, 5 membered saturated heterocyclic group, and benzo(6 membered saturated)heterocyclic group;
the substituent of the alkyl is selected from halogen, benzo(5 membered saturated)heterocyclic group, substituted or unsubstituted aryl, 6 membered saturated heterocyclic group, hydroxyl, —N(H)C(O)OR51, —C(O)R51, and —NR52R53;
the substituent of the aryl is selected from halogen, C1 alkoxyl, cyano, nitro, and substituted or unsubstituted C1 alkyl;
R52 and R53 are each independently C1-C1 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O, N and S;
the unsaturated heterocyclic group comprises one or two N.

### Claim 12 (depends on 1, 9)

The method according to claim 9, wherein the compound according to claim 1 has a structure of formula IIA:
wherein, R21, R22, R23, and R24 are each independently selected from H, —C(O)OR51, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, —N(H)C(O)R51, 6 membered saturated cycloalkyl, —C(O)R51, 6-membered saturated heterocyclic group, carbazolyl, amino, hydroxyl, nitro, —S(O)(O)R51, aryl, cyano, halogen, and —C(O)N(H)R51;
R51 is selected from H, C1-C2 alkyl, amino, substituted or unsubstituted aryl, substituted or unsubstituted 5-6 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently of selected from H, substituted or unsubstituted 6 membered saturated heterocyclic group, substituted or unsubstituted C1-C4 alkyl, and 4 membered cycloalkyl;
the substituent of the alkyl is selected from halogen and substituted or unsubstituted 6 membered saturated heterocyclic group;
the substituent of the alkoxyl is selected from halogen and aryl;
the substituent of the aryl is substituted C1 alkyl;
the substituent of the saturated heterocyclic group is C1 alkyl; said saturated heterocyclic group comprises one or two heteroatoms selected from N and O,
or, said compound has a structure of formula IIB:
wherein, R25 is substituted or unsubstituted 6-7 membered saturated heterocyclic group;
the substituent of the saturated heterocyclic group is C1 alkyl;
said heterocyclic group comprises two heteroatoms selected from N and O;
or, said compound has a structure of formula IIC:
wherein, R26 is selected from —N(H)C(O)R51, amino, and 6 membered saturated heterocyclic group;
said saturated heterocyclic group comprises two heteroatoms selected from N and O;
R51 is C1 alkyl;
or, said compound has a structure of formula IIIA:
wherein, R31, R32, R33 are each independently selected from H, halogen, cyano, hydroxyl, amino, substituted or unsubstituted C1-C3 alkoxy, —C(O)OR51, —N(H)C(O)R51, aryl, phenoxy, —NR52R53, substituted 6 membered saturated heterocyclic group, and nitro, with the proviso that all of R31, R32, and R33 are not simultaneously H;
R51 is C1-C4 alkyl;
the substituent of the alkyl is halogen;
the substituent of the alkoxyl is selected from aryl and halogen;
the substituent of the saturated heterocyclic group is C1 alkyl;
the saturated heterocyclic group comprises two N;
R52 and R53 are each independently aryl;
or, said compound has a structure of formula IIIB:
wherein, ring B is selected from benzo(5-6 membered saturated)heterocyclic group, benzo(5 membered unsaturated)heterocyclic group, anthryl, substituted 6 membered unsaturated heterocyclic group, and 6 membered saturated cycloalkyl;
the substituent of the unsaturated heterocyclic group is selected from cyano, C1 alkyl, and C2 alkoxyl;
the saturated heterocyclic group comprises one or two O;
the unsaturated heterocyclic group comprises one heteroatom selected from O and N;
or, said compound has a structure of formula IVA:
wherein, R41, R42, R43, and R44 are each independently selected from H, hydroxyl, —N(H)C(O)OR51, and substituted or unsubstituted C1 alkyl;
R51 is C4 alkyl;
the substituent of the alkyl is —N(H)C(O)OR51;
or, said compound has a structure of formula IVB:
wherein, R41′, R42′, R43′, and R44′ are each independently selected from H and hydroxyl;
or, said compound has a structure of formula IVC:
wherein, R41″, R42″, R43″, and R44″ are each independently selected from H, C1 alkyl, and —C(O)R51;
R51 is C1 alkyl;
or, said compound has a structure of formula IVD:
wherein, R45, R46, R47, and R48 are each independently selected from H, substituted or unsubstituted C1-C4 alkyl, —C(O)R51, —S(O)(O)R51, 6 membered unsaturated heterocyclic group, —C(O)OR51, and substituted or unsubstituted aryl;
R51 is selected from 5 membered saturated heterocyclic group, C1-C4 alkyl, and benzo(6 membered saturated)heterocyclic group;
R52 and R53 are each independently C1 alkyl;
the substituent of the alkyl is selected from halogen, benzo(5 membered saturated)heterocyclic group, —C(O)R51, —NR52R53, substituted or unsubstituted aryl, 6 membered saturated heterocyclic group, and hydroxyl;
the substituent of the aryl is selected from C1 alkoxyl, halogen, cyano, nitro, and substituted or unsubstituted C1 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O and N;
the unsaturated heterocyclic group comprises one or two N;
or, said compound has a structure of formula IVE:
Wherein, R45′, R46′, R47′, and R48′ are each independently selected from H and C1 alkyl;
or, said compound has a structure of formula IVF:
wherein, R45″, R46″, R47″, and R48″ are each independently selected from H and C1 alkyl;
or, said compound has a structure of formula IVG:
wherein, R45′″, R46′″, R47′″, and R48′″ are each independently selected from H, hydroxyl, —C(O)OR51, —N(H)C(O)OR51, substituted aryl, substituted or unsubstituted C1 alkyl, 6 membered saturated heterocyclic group, and —C(O)R51;
R51 is selected from C2-C4 alkyl and amino;
the substituent of the aryl is halogen;
the substituent of the alkyl is selected from —N(H)C(O)OR51 and hydroxyl;
the saturated heterocyclic group comprises one N.

### Claim 13 (depends on 1, 9)

The method according to claim 9, wherein the compound according to claim 1 is selected from:

### Claim 14 (depends on 1)

A pharmaceutical preparation, comprising the compound or the pharmaceutically acceptable salt, or the solvate thereof according to claim 1, as active ingredients, and one or more pharmaceutically acceptable excipients; wherein, said pharmaceutical preparation is an oral preparation or an intravenous injection preparation.

### Claim 15 (depends on 1, 14)

The pharmaceutical preparation according to claim 14, wherein, in the compound according to claim 1, when the dotted line is a bond,
R1 is selected from 3-8 membered unsaturated cycloalkyl, and 3-8 membered unsaturated heterocyclic group, all of which are substituted by m R2;
m is an integer of 0-4;
R2 is selected from substituted or unsubstituted C1-C6 linear or branched chain alkyl, substituted or unsubstituted C1-C6 alkoxy, 3-8 membered saturated cycloalkyl, substituted or unsubstituted 3-8 membered saturated heterocyclic group, 3-8 membered unsaturated cycloalkyl, carbazolyl, amino, hydroxyl, nitro, cyano, halogen, —C(O)OR51, —N(H)C(O)R51, —C(O)R51, —S(OXO)R51, and —C(O)N(H)R51;
R51 is selected from H, C1-C4 linear or branched chain alkyl, amino, substituted or unsubstituted 3-8 membered unsaturated cycloalkyl, substituted or unsubstituted 5-8 membered saturated heterocyclic group, and_—NR52R53;
R52 and R53 are each independently selected from H, substituted or unsubstituted 5-8 membered saturated heterocyclic group, substituted or unsubstituted C1-C6 linear or branched chain alkyl, and 3-6 membered saturated cycloalkyl;
the substituents of the alkyl are selected from halogen and substituted or unsubstituted 5-8 membered saturated heterocyclic group;
the substituents of the alkoxyl are selected from halogen and 3-8 membered unsaturated cycloalkyl;
the substituent of the unsaturated cycloalkyl is C1-C4 alkyl;
the substituent of the saturated heterocyclic group is C1-C4 alkyl;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O;
the saturated heterocyclic group comprises one or two heteroatoms selected from N and O;
When the dotted line is none,
R1 is selected from 3-8 membered unsaturated cycloalkyl, benzo(5-8 membered saturated)heterocyclic group, benzo(5-8 membered unsaturated)heterocyclic group, anthryl, 3-8 membered unsaturated heterocyclic group, 3-8 membered saturated cycloalkyl, all of which are substituted by n R3, or R1 is S(O)(O)R1′;
n is an integer of 1-4;
R3 is selected from halogen, cyano, hydroxyl, amino, nitro, 3-8 membered unsaturated cycloalkyl, phenoxyl, substituted 5-8 membered saturated heterocyclic group, substituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, —C(O)OR51, —N(H)C(O)R51, and —NR52R53;
R1′ is 3-8 membered saturated heterocyclic group substituted by p R4;
p is an integer of 0-4;
R4 is selected from hydroxyl, substituted or unsubstituted C1-C6 alkyl, —C(O)R51, —N(H)C(O)OR51, —S(O)(O)R51, —C(O)OR51, 3-8 membered unsaturated heterocyclic group, 3-8 membered saturated heterocyclic group, and substituted or unsubstituted 3-8 membered unsaturated cycloalkyl;
R51 is selected from C1-C8 alkyl, amino, 5-8 membered saturated heterocyclic group, and benzo(5-8 membered saturated)heterocyclic group;
R52 and R53 are each independently selected from 3-8 membered unsaturated cycloalkyl, and C1-C4 alkyl;
the substituents of the alkyl are selected from halogen, benzo(5-8 membered saturated)heterocyclic group, substituted or unsubstituted 3-8 membered unsaturated cycloalkyl, 5-10 membered saturated heterocyclic group, hydroxyl, —N(H)C(O)OR51, —C(O)R51, and —NR52R53;
the substituents of the alkoxyl are selected from 3-8 membered unsaturated cycloalkyl and halogen;
the substituents of the unsaturated cycloalkyl are selected from halogen, C1-C4 alkoxyl, cyano, nitro, and substituted or unsubstituted C1-C4 alkyl;
the substituent of the saturated heterocyclic group is C1-C4 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O, N, and S;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O.

### Claim 16 (depends on 1, 14)

The pharmaceutical preparation according to claim 14, wherein, in the compound according to claim 1 has a structure of formula II:
wherein, ring A is selected from aryl substituted by m R2 and heteroaryl substituted by m R2; said heteroaryl comprises one or two N, and
m is an integer of 0-4;
R2 is selected from H, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, 6-8 membered saturated cycloalkyl, substituted or unsubstituted 6-7 membered saturated heterocyclic group, carbazolyl, amino, hydroxyl, nitro, aryl, cyano, halogen, —C(O)OR51, —N(H)C(O)R51, —C(O)R51, —S(O)(O)R51, and —C(O)N(H)R51;
R51 is selected from H, C1-C2 alkyl, amino, substituted or unsubstituted aryl, substituted or unsubstituted 5-6 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently selected from H, substituted or unsubstituted 6-8 membered saturated heterocyclic group, substituted or unsubstituted C1-C4 linear or branched chain alkyl, and 4-5 membered saturated cycloalkyl;
the substituents of the alkyl are selected from halogen and substituted or unsubstituted 6-8 membered saturated heterocyclic group;
the substituents of the alkoxyl are selected from halogen and aryl;
the substituent of the aryl is substituted C1-C3 alkyl;
the substituent of the saturated heterocyclic group is C1-C3 alkyl; said heterocyclic group comprises one or two heteroatoms selected from N and O,
or, said compound has a structure of formula III:
wherein, ring B is selected from aryl, benzo(5-6 membered saturated)heterocyclic group, benzo(5 membered unsaturated)heterocyclic group, anthryl, 6-8 membered unsaturated heterocyclic group or 6-8 membered saturated cycloalkyl, all of which are substituted by n R3,
n is an integer of 1-3;
R3 is selected from H, halogen, cyano, hydroxyl, amino, nitro, aryl, phenoxy, substituted 6-8 membered saturated heterocyclic group, substituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, —C(O)OR51, —N(H)C(O)R51, and —NR52R53;
R51 is C1-C4 alkyl,
R52 and R53 are each independently aryl;
the substituent of the alkyl is halogen;
the substituents of the alkoxyl are aryl and halogen;
the substituent of the saturated heterocyclic group is C1-C2 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from N and O;
the unsaturated heterocyclic group comprises one or two heteroatoms selected from N and O;
or, said compound has a structure of formula IV:
wherein, ring C is a 5-8 membered saturated heterocyclic group substituted by p R4;
p is an integer of 0-4,
R4 is selected from H, hydroxyl, substituted or unsubstituted C1-C4 alkyl, —C(O)R51, —N(H)C(O)OR51, —S(O)(O)R51, —C(O)OR51, 6-8 membered unsaturated heterocyclic group, 6-8 membered saturated heterocyclic group, and substituted or unsubstituted aryl;
R51 is selected from C1-C4 alkyl, amino, 5 membered saturated heterocyclic group, and benzo(6 membered saturated)heterocyclic group;
The substituents of the alkyl are selected from halogen, benzo(5 membered saturated)heterocyclic group, substituted or unsubstituted aryl, 6 membered saturated heterocyclic group, hydroxyl, —N(H)C(O)OR51, —C(O)R51, and —NR52R53;
the substituents of the aryl are selected from halogen, C1 alkoxyl, cyano, nitro, and substituted or unsubstituted C1 alkyl;
R52 and R53 are each independently C1-C1 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O, N, and S; and
the unsaturated heterocyclic group comprises one or two N.

### Claim 17 (depends on 1, 14)

The pharmaceutical preparation according to claim 14, wherein the compound according to claim 1 has a structure of formula IIA:
wherein, R21, R22, R23, and R24 are each independently selected from H, —C(O)OR51, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C3 alkoxy, —N(H)C(O)R51, 6 membered saturated cycloalkyl, —C(O)R51, 6-membered saturated heterocyclic group, carbazolyl, amino, hydroxyl, nitro, —S(OXO)R51, aryl, cyano, halogen, and —C(O)N(H)R51;
R51 is selected from H, C1-C2 alkyl, amino, substituted or unsubstituted aryl, substituted or unsubstituted 5-6 membered saturated heterocyclic group, and —NR52R53;
R52 and R53 are each independently of selected from H, substituted or unsubstituted 6 membered saturated heterocyclic group, substituted or unsubstituted C1-C4 linear or branched chain alkyl, and 4 membered cycloalkyl;
the substituents of the alkyl are selected from halogen and substituted or unsubstituted 6 membered saturated heterocyclic group;
the substituents of the alkoxyl are selected from halogen and aryl;
the substituent of the aryl is substituted C1 alkyl;
the substituent of the saturated heterocyclic group is C1 alkyl; said saturated heterocyclic group comprises one or two heteroatoms selected from N and O,
or, said compound has a structure of formula IIB:
wherein, R25 is selected from substituted or unsubstituted 6-7 membered saturated heterocyclic group;
the substituent of the saturated heterocyclic group is C1 alkyl;
said heterocyclic group comprises two heteroatoms selected from N and O;
or, said compound has a structure of formula IIC:
wherein, R26 is selected from —N(H)C(O)R51, amino, and 6 membered saturated heterocyclic group;
said saturated heterocyclic group comprises two heteroatoms selected from N and O;
R51 is C1 alkyl;
or, said compound has a structure of formula IIIA:
wherein, R31, R32, R33 are each independently selected from H, halogen, cyano, hydroxyl, amino, substituted or unsubstituted C1-C3 alkoxy, —C(O)OR51, —N(H)C(O)R51, aryl, phenoxy, —NR52R53, substituted 6 membered saturated heterocyclic group, and nitro, with the proviso that all of R31, R32, and R33 are not simultaneously H;
R51 is C1-C4 alkyl;
the substituent of the alkyl is halogen;
the substituents of the alkoxyl are selected from aryl and halogen;
the substituent of the saturated heterocyclic group is C1 alkyl;
the saturated heterocyclic group comprises two N;
R52 and R53 are each independently aryl;
or, said compound has a structure of formula IIIB:
wherein, ring B is selected from benzo(5-6 membered saturated)heterocyclic group, benzo(5 membered unsaturated)heterocyclic group, anthryl, and substituted 6 membered unsaturated heterocyclic group or 6 membered saturated cycloalkyl;
the substituents of the unsaturated heterocyclic group are selected from cyano, C1 alkyl, and C2 alkoxyl;
the saturated heterocyclic group comprises one or two O;
the unsaturated heterocyclic group comprises one heteroatom selected from O and N;
or, said compound has a structure of formula IVA:
wherein, R41, R42, R43, and R44 are each independently selected from H, hydroxyl, —N(H)C(O)OR51, and substituted or unsubstituted C1 alkyl;
R51 is C4 alkyl;
the substituent of the alkyl is —N(H)C(O)OR51;
or, said compound has a structure of formula IVB:
wherein, R41′, R42′, R43′, and R44′ are each independently selected from H and hydroxyl;
or, said compound has a structure of formula IVC:
wherein, R41″, R42″, R43″, and R44″ are each independently selected from H, C1 alkyl, and —C(O)R51;
R51 is C1 alkyl;
or, said compound has a structure of formula IVD:
wherein, R45, R46, R47, and R48 are each independently selected from H, substituted or unsubstituted C1-C4 alkyl, —C(O)R51, —S(O)(O)R51, 6 membered unsaturated heterocyclic group, —C(O)R51, and substituted or unsubstituted aryl;
R51 is selected from 5 membered saturated heterocyclic group, C1-C4 alkyl, and benzo(6 membered saturated)heterocyclic group;
R52 and R53 are each independently C1 alkyl;
the substituents of the alkyl are selected from halogen, benzo(5 membered saturated)heterocyclic group, —C(O)R51, —NR52R53, substituted or unsubstituted aryl, 6 membered saturated heterocyclic group, and hydroxyl;
the substituents of the aryl are selected from C1 alkoxyl, halogen, cyano, nitro, and substituted or unsubstituted C1 alkyl;
the saturated heterocyclic group comprises one or two heteroatoms selected from O and N;
the unsaturated heterocyclic group comprises one or two N;
or, said compound has a structure of formula IVE:
wherein, R45′, R46′, R47′, and R48′ are each independently selected from H and C1 alkyl;
or, said compound has a structure of formula IVF:
wherein, R45″, R46″, R47″, and R48″ are each independently selected from H and C1 alkyl;
or, said compound has a structure of formula IVG:
wherein, R45′″, R46′″, R47′″, and R48′″ are each independently selected from H, hydroxyl, —C(O)OR51, —N(H)C(O)OR51, substituted aryl, substituted or unsubstituted C1 alkyl, 6 membered saturated heterocyclic group, and —C(O)R51;
R51 is selected from C2-C4 alkyl and amino;
the substituent of the aryl is halogen;
the substituents of the alkyl are selected from —N(H)C(O)OR51 and hydroxyl; and
the saturated heterocyclic group comprises one N.

### Claim 18 (depends on 1, 14)

The pharmaceutical preparation according to claim 14, wherein the compound according to claim 1 is selected from:

### Claim 19 (depends on 1)

A method for treating stroke, comprising: administering a pharmaceutically acceptable amount of the compound, or the pharmaceutically acceptable salt, or the solvate thereof according to claim 1 to a subject in need thereof.

### Claim 20 (depends on 19)

The method of claim 19, wherein the compound is A38: