Aromatic fused ring imine compound as well as preparation method and application thereof

Abstract

The invention relates to an aromatic fused ring imine compound as well as a preparation method and application thereof. The aromatic condensed ring imine compound has a rigid planar structure and a plurality of hydrogen bond acceptors and donors, and the rigid planar structure can generate pi-pi accumulation with aromatic amino acid residues exposed in a solution in a chitinase binding pocket; a hydrogen bond acceptor (such as a carbonyl oxygen atom) and a hydrogen bond donor can generate direct or water-mediated hydrogen-bond interaction with amino acid in a binding pocket, so that an inhibition effect on chitinase is generated, and evaluation and research on the inhibition effect and selectivity of the chitinase can be known, and the application prospect is wide. The aromatic condensed ring imine compound shows inhibitory activity on chitinase of Asiatic corn borer, human beings, caenorhabditis elegans, brugia malayi, aspergillus fumigatus and serratia marcescens, and has a wide application prospect in the fields of biology and biochemistry.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical chemistry, and in particular to an aromatic condensed ring imine compound and a preparation method and application thereof. Background Art

[0002] Chitin is a natural linear straight-chain polysaccharide with N-acetyl-β-D-glucosamine (GlcNAc) as the basic unit and connected by β-1,4 glycosidic bonds. It is an important component of insect exoskeleton and midgut peritrophic membrane, nematode egg shell, mollusk shell, and fungal cell wall. Its synthesis and degradation play an important role in the growth and development of these organisms. GH18 family chitinase is a key enzyme for hydrolyzing chitin. Inhibition of chitinase related to insect and nematode molting, such as chitinase OfChi-h and OfChtI from corn borer, nematode chitinase CeCht1, and Brugia malayi chitinase BmCht1, will cause insects and nematodes to fail to molt, growth inhibition, pupation failure and death, and can be used as a potential target for pesticide research and development. The human body expresses two chitinases and multiple chitinase proteins. The expression of human chitotriose chitinase HsChit1 is associated with pulmonary fibrosis and can be used as a potential target for the treatment of specific pulmonary fibrosis; the overexpression of human acidic mammalian enzyme AMCase is associated with asthma and can be used as a potential target for the treatment of asthma. In recent years, important progress has been made in the analysis of the crystal structures of multiple chitinases, providing an important theoretical basis for the rational design of small molecule chitinase inhibitors for agricultural and medical use.

[0003] Chitinase plays an important role in fungal infection, insect molting, nematode hatching, and human asthma and pulmonary fibrosis. Therefore, inhibitors targeting chitinase have good application prospects and positive research significance in the development of antifungal agents, insecticides, nematicides and lung disease drugs. Summary of the invention

[0004] The purpose of the present invention is to provide an aromatic condensed ring imine compound and a preparation method and application thereof. The compound of the present invention has broad application prospects in inhibiting agricultural pests, being used for specific pulmonary fibrosis, resisting fungal infection and inhibiting bacterial growth.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] An aromatic fused ring imine compound of the general formula (I), or an optical isomer, cis-trans isomer or a pharmaceutically or pesticide-acceptable salt or solvate thereof:

[0007]

[0008] Wherein, Y is none, or a substituted or unsubstituted alkylene or alkylene-O- having 1 to 10 carbon atoms, wherein the alkylene is a straight chain or branched chain alkylene;

[0009] M is selected from the group consisting of NH, O or S;

[0010] R1 is located at One or more H or C1-C4 alkyl or halogen in the ring;

[0011] R2, R3 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, hydroxyl, amino, thiol, phosphino, nitro, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl;

[0012] R4 is selected from the group consisting of hydrogen, halogen, hydroxy, nitro, amino, cyano, carbonyl, substituted or unsubstituted C2-C 12 Alkenyl, substituted or unsubstituted C2-C 12 Alkynyl, Carboxyl, substituted or unsubstituted C1-C 12 Alkyl or alkoxy, substituted or unsubstituted C1-C 12 Alkylamino, substituted or unsubstituted C3-C9 cycloalkyl, substituted or unsubstituted C 5-7 Cycloalkenyl, substituted or unsubstituted C2-C9 non-heteroaryl, substituted or unsubstituted 3-12 membered heterocyclic ring, substituted or unsubstituted C6-C 12 Aryl, substituted or unsubstituted C4-C 12 Heteroaryl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-membered or 6-membered heterocyclic group, or substituted or unsubstituted 8-12-membered heteroaromatic bicyclic group;

[0013] Ring A is a substituted or unsubstituted 8-12 membered heteroaromatic bicyclic ring system, a substituted or unsubstituted 8-12 membered heteroaromatic tricyclic ring system, a substituted or unsubstituted 5-12 membered aromatic ring system, a substituted or unsubstituted 5-12 membered heterocyclic ring system, a substituted or unsubstituted 5-12 membered aromatic ring, a substituted or unsubstituted 5-12 membered heteroaromatic ring, or a substituted or unsubstituted 5-12 membered heterocyclic ring (including a fully or partially unsaturated heterocyclic ring);

[0014] R5 is a substituent located at any one or more positions of the ring A, each independently, and R5 is selected from the following group: halogen, cyano, nitro, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 2-6 Alkenyl, substituted or unsubstituted C 2-6 Alkynyl, or substituted or unsubstituted C 3-7Cycloalkyl, substituted or unsubstituted C 5-7 Cycloalkenyl, trimethylsilylethynyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, trimethylsilylethynyl, substituted or unsubstituted 5- or 6-membered heterocyclyl, substituted or unsubstituted 8- to 12-membered heteroaromatic bicyclic ring system, OR', Si(R')3, NR'R", C(O)R', C(O)OR', C(O)NR'R", SR', S(O) m R', S(O)2NR'R", OC(O)R', OC(O)NR'R", OS(O)2R', OS(O)2NR'R", N(R")C(O)R', NCH2R', N(R")C(O)NR'R", N(R")S(O)2R' or N(R')S(O)2NR'R";

[0015] Wherein, the substitution refers to that one or more hydrogen atoms on the group are replaced by a substituent selected from the following group: halogen, hydroxyl, nitro, amino, cyano, carbonyl, carboxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, hydroxyl C1-C6 alkyl, amino C1-C6 alkyl, carbonyl C1-C6 alkyl, OR', Si(R')3, NR'R", C(O)R', C(O)OR', C(O)NR'R", SR', S(O) m R', S(O)2NR'R", OC(O)R', OC(O)NR'R", OS(O)2R', OS(O)2NR'R", N(R")C(O)R' , NCH2R', N(R")C(O)NR'R", N(R")S(O)2R' or N(R')S(O)2NR'R", C3-C9 cycloalkyl, C6-C 12 Aryl, 3-12 membered heterocyclic ring, C4-C 12 heteroaryl;

[0016] Wherein R' and R" are independently: H, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Halogenated cycloalkyl, C 2-6 Alkenyl, C 2-6 Halogenated alkenyl, C 2-6 Alkynyl, C 2-6 Haloalkynyl, substituted or unsubstituted C 3-7 Cycloalkyl, substituted or unsubstituted C 5-7 cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-membered or 6-membered saturated or unsaturated heterocyclic group, or substituted or unsubstituted 8-membered to 12-membered heteroaromatic bicyclic ring system; wherein the substituents on R' and R" are substituted by one or more groups selected from the group consisting of oxy (=O), halogen, cyano, nitro, C1-6 Alkyl or cycloalkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Halogenated alkenyl, C 2-6 Alkynyl, C 2-6 Haloalkynyl, hydroxyl, hydroxyl C 1-4 alkyl.

[0017] In one embodiment of the present invention, the compound has a structure as shown in formula (II), formula (III), formula (IV) or formula (V):

[0018]

[0019] wherein Y is none, or an unsubstituted straight chain alkylene or alkylene-O- having 1 to 10 carbon atoms;

[0020] M is selected from the group consisting of NH, O or S;

[0021] n is 0, 1, 2, 3;

[0022] R1 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, ethyl, propyl, isopropyl, cyclopropyl, n-butyl or tert-butyl;

[0023] R2, R3 are each independently selected from the following group: hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, isobutylhydroxy, amino, mercapto, phosphino, nitro, phenyl, benzyl, pyridyl, furyl, thienyl, methoxyphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1,2-dichlorophenyl, 1,3-dichlorophenyl, 1,4-dichlorophenyl, 1, 2-Dibromophenyl, 1,3-dibromophenyl, 1,4-dibromophenyl, 1,2-difluorophenyl, 1,3-difluorophenyl, 1,4-difluorophenyl, 1,2-dimethylphenyl, 1,3-dimethylphenyl, 1,4-dimethylphenyl, 1,2,4,5-tetrafluorophenyl, 1,2,3,4-tetrafluorophenyl, 1,2,3,5-tetrafluorophenyl, 1,2,4,5-tetrabromophenyl, 1,2,3,4-tetrabromophenyl, 1,2,3,5-tetrabromophenyl, 1,2,4,5-tetrachlorophenyl, 1,2,3,4-tetrachlorophenyl, 1,2,3,5-tetrachlorophenyl;

[0024] R4, R5 are each independently selected from the following group: hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxy 2,3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperid ... 4-oxazine)phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

[0025] In one embodiment of the present invention, the compound has the structure shown below:

[0026]

[0027] Y is none, or an unsubstituted straight chain alkylene group having 1, 2, or 3 carbon atoms;

[0028] R4, R5 are each independently selected from the following group: hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxy 2,3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperid ... 4-oxazine)phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

[0029] In one embodiment of the present invention, the compound has the structure shown below:

[0030]

[0031] R4, R5 are each independently selected from the following group: hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxy 2,3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperid ... 4-oxazine)phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

[0032] In one embodiment of the present invention, the compound has the structure shown below:

[0033]

[0034] R2, R3 are each independently selected from the following group: hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, isobutylhydroxy, amino, mercapto, phosphino, nitro, phenyl, benzyl, pyridyl, furyl, thienyl, methoxyphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1,2-dichlorophenyl, 1,3-dichlorophenyl, 1,4-dichlorophenyl, 1, 2-Dibromophenyl, 1,3-dibromophenyl, 1,4-dibromophenyl, 1,2-difluorophenyl, 1,3-difluorophenyl, 1,4-difluorophenyl, 1,2-dimethylphenyl, 1,3-dimethylphenyl, 1,4-dimethylphenyl, 1,2,4,5-tetrafluorophenyl, 1,2,3,4-tetrafluorophenyl, 1,2,3,5-tetrafluorophenyl, 1,2,4,5-tetrabromophenyl, 1,2,3,4-tetrabromophenyl, 1,2,3,5-tetrabromophenyl, 1,2,4,5-tetrachlorophenyl, 1,2,3,4-tetrachlorophenyl, 1,2,3,5-tetrachlorophenyl;

[0035] R4, R5 are each independently selected from the following group: hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxy 2,3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperid ... 4-oxazine)phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

[0036] In one embodiment of the present invention, Y, R1, R2, R3, R4, R5, M and ring A are each independently a group corresponding to the specific compound in the embodiment.

[0037] In the above further aspect, said R5 is selected from hydrogen or methyl.

[0038] In the above further, the R1 is located at A methyl group on the ring.

[0039] The preferred compounds of the general formula (I) provided by the present invention include but are not limited to the structures of the aromatic fused ring imine compounds 01-98 in Table 1.

[0040] A method for preparing an aromatic condensed ring imine compound, the specific steps are as follows:

[0041]

[0042] The compound of formula I-V is obtained by reacting the compound of formula I-VA with the compound of formula I-VB in an inert solvent.

[0043] An aromatic fused ring imine compound, or an optical isomer, a cis-trans isomer or a pharmaceutically and pesticide-acceptable salt or solvate of the compound, is used in the preparation of a chitinase inhibitor for inhibiting the activity of family 18 chitinases. The final concentration of the compound used in inhibiting the activity of family 18 chitinases is not less than 1 μM.

[0044] Further, the application is selected from the following: application in delaying the growth and development of lepidopteran pests and the hatching of nematode eggs; application in specific pulmonary fibrosis, asthma, anti-fungal infection and inhibition of bacterial growth.

[0045] A kind of aromatic condensed ring imine derivatives, based on the aromatic condensed ring imine compounds, the derivatives are optical isomers, cis-trans isomers, pharmaceutically and pesticide-acceptable salts or solvates of the compounds of formula (I), (II), (III), (IV) and (V), and the salts or solvates are used in the chitinase of agricultural pests or humans, fungi or bacteria.

[0046] Furthermore, the agricultural pests are lepidopteran insects and nematodes.

[0047] Furthermore, the lepidopteran insects include wheat moth, pink bollworm, potato tuber moth, sweet potato wheat moth, cotton brown-banded moth, soybean borer, pear borer, Asian corn borer, large bridge-building insect, cabbage butterfly, cotton bollworm, gypsy moth, jade butterfly, swallowtail butterfly, boat caterpillar, yellow-bellied moth, American white moth, grape hawkworm and rice sheathworm, etc.; the nematodes are Caenorhabditis elegans, Malayan filaria, root-knot nematode, cyst nematode, Heterodera nematode, seed-nodule nematode, pine nematode, root rot nematode and cone nematode.

[0048] Furthermore, the human chitinase is chitotriose chitinase, an acidic mammalian enzyme; the fungal chitinase is Aspergillus fumigatus chitinase; and the bacterial chitinase is Serratia marcescens chitinase.

[0049] Furthermore, the application in preventing and controlling agricultural pests is the application in delaying the growth and development of lepidopteran pests and the hatching of nematode eggs, and the application in preventing and controlling human chitinase or fungal and bacterial chitinase is the application in specific pulmonary fibrosis, asthma, anti-fungal infection and inhibiting bacterial growth.

[0050] A pharmaceutical composition, comprising a therapeutically effective amount of the aromatic fused ring imine compound, a pharmaceutically and pesticidely acceptable salt or a pharmaceutically and pesticidely acceptable solvate thereof as an active ingredient, and a pharmaceutically and pesticidely acceptable carrier.

[0051] Compared with the prior art, the present invention has the following advantages:

[0052] 1) The aromatic fused ring imine compounds of the present invention have chitinase (such as corn borer chitinase OfChi-h, Caenorhabditis elegans chitinase CeCht1, Brugia malayi chitinase BmCht1 and human chitotriose chitinase HsChit1, etc.) inhibitory activity. Through the evaluation and study of its inhibitory effect and selectivity, it can be known that the aromatic fused ring imine compounds show inhibitory activity against chitinases of Asian corn borer, humans, Caenorhabditis elegans, Brugia malayi, Aspergillus fumigatus, and Serratia marcescens, and have a wide range of application scenarios in the fields of biology and biochemistry;

[0053] 2) The data obtained from the inhibitory activity of the inhibitors, including inhibition percentage and inhibition constant determination, showed that this type of structure exhibited a wide range of inhibitory activities, showing certain inhibitory activities against OfChi-h, OfChtI, SmChiB, CeCht1, HsChit1, AmCase, and BmCht1;

[0054] 3) In particular, the inhibition rates of compound 08 on OfChi-h, CeCht1, HsChit1 and AmCase in the corresponding table were all above 90%, and the K of compound 08 on chitinase OfChi-h of Asian corn borer was i The K of human HsChit1 is 40.7 nM. i The K of human AmCase is 12.1 nM. i The K of CeCht1 was 64.1 nM. i 18.8nM;

[0055] 4) The aromatic fused ring imine compounds of the present invention have a rigid planar structure and multiple hydrogen bond acceptors and donors. The rigid planar structure can undergo π-π stacking with the aromatic amino acid residues exposed to the solution in the chitinase binding pocket, and the hydrogen bond acceptors (such as carbonyl oxygen atoms) and hydrogen bond donors can produce direct or water-mediated hydrogen bonds with the amino acids in the binding pocket, thereby producing an inhibitory effect on chitinase. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] Figure 1 This is a test chart of the inhibitory activity of 08 on the chitinase OfChi-h of Asian corn borer;

[0057] Figure 2 This is a test diagram of the inhibitory activity of 08 on human chitotriose chitinase HsChit1;

[0058] Figure 3 This is a test diagram of the inhibitory activity of 08 on the chitinase CeCht1 of Caenorhabditis elegans;

[0059] Figure 4 This is a test chart of the inhibitory activity of 08 on the acidic mammalian enzyme AMCase. DETAILED DESCRIPTION

[0060] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0061] Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood in the art to which this invention belongs.

[0062] The term "C 1-6 The term "alkyl" refers to a straight or branched chain alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or the like.

[0063] The term "C1-C6 alkoxy" refers to a substituent of a structure such as "a straight-chain or branched alkyl-oxy group having 1 to 6 carbon atoms", such as ethoxy, propoxy, butoxy, or the like.

[0064] The term "C1-C6 alkylamino" refers to a substituent having a structure of "a straight-chain or branched alkyl-amino group having 1 to 6 carbon atoms", such as ethylamino, propylamino, dimethylamino, or a similar group.

[0065] The term "alkylene" refers to a group formed after the alkyl group described above loses a hydrogen atom, for example, -CH2-, -CH2-CH2-, or the like.

[0066] The term "C2-C 12 The term "alkenyl" refers to a straight or branched alkenyl group of an olefin having 2 to 12 carbon atoms, including ethenyl, propenyl, n-alkenyl, or the like.

[0067] The term "C3-C9 cycloalkyl" refers to a cycloalkyl group having 3 to 9 carbon atoms, such as cyclopropane, cyclohexane, and the like.

[0068] The term "halogen" refers to F, Cl, Br and I. The term "halogenated" refers to groups substituted by the same or different one or more of the above halogen atoms, for example trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, or the like.

[0069] The term "ring" or "ring system" refers to a carbocyclic or heterocyclic ring.

[0070] The term "heterocycle" refers to at least one atom in the atoms forming the heterocycle skeleton that is not carbon, but nitrogen, oxygen or sulfur. Typically, the heterocycle contains no more than 4 nitrogens, no more than 2 oxygens and / or no more than 2 sulfurs. Unless otherwise indicated, the heterocycle can be a saturated, partially unsaturated or fully unsaturated ring. In a preferred embodiment of the present invention, the heterocycle contains 1-4 heteroatoms independently selected from N, S and O.

[0071] The term "ring system" refers to two or more rings fused together.

[0072] The term "5-membered or 6-membered heterocyclyl" refers to a five-membered or six-membered ring containing one or more heteroatoms selected from nitrogen, oxygen or sulfur, for example pyridyl, thiazolyl, isothiazolyl, thienyl, furanyl, pyrrolyl, pyrazolyl, pyrimidinyl, tetrahydrofuranyl, 4,5-dihydrothiazol-2-yl, 2-cyanoimino-4-oxo-1,3-thiazolidin-3-yl, 2-cyanoimino-4-oxo-1,3-thiazin-3-yl, oxazolyl, isoxazolyl, 1H-tetrazolyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl or tetrazolyl, etc. The term "C4-C 12"Heteroaryl" refers to an unsaturated ring system substituent having 4 to 12 carbon atoms and having one or more heteroatoms selected from O, S, N or P, such as pyridyl, thienyl, or the like.

[0073] The term "heterocyclic ring system" refers to a ring system wherein at least one ring in the ring system is a heterocyclic ring.

[0074] The term "heteroaromatic ring system" refers to a system in which at least one ring in the ring system is aromatic.

[0075] The term "8- to 12-membered heteroaromatic bicyclic ring system" or "8- to 14-membered heteroaromatic bicyclic or tricyclic ring system" may be selected from the group consisting of benzofuran, benzo[b]thiophene, indole, quinoline, isoquinoline, 1H-indazole, 1H-benzo[d]imidazole, benzo[d]thiazole, benzo[d]oxazole, benzo[d]isoxazole, benzo[d][1,2,3]thiadiazole, 2,3-dihydroimidazo[1,2-a]pyridine, quinazoline, quinoxaline, cinnoline, phthalazine, 1,8-naphthyridine, 4,5,6,7-tetrahydro Benzo[b]thiophene, benzo[b]thiophene-1,1-dioxane, 8H-indeno[2,1-b]thiophene, 7,8-dihydro-6H-cyclopenta[4,5]thieno[2,3-d]pyrimidine, 3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one, spiro[indoline-3,2'-[1,3]dioxolane]-2-one, spiro[indoline-3,2'-[1,3]dioxane]-2-one, or indoline-2,3-dione, etc.

[0076] The term "alkyl" refers to a group formed by removing one hydrogen atom from an alkane molecule; the term "alkylene" refers to a group formed by removing two hydrogen atoms from an alkane molecule. Similarly, the definitions of "alkenylene", "alkynylene", "cycloalkylene", "cycloalkenylene", "phenylene", "naphthylene", "heterocyclylene" or "heteroaromatic bicyclic or tricyclic ring system" are similar.

[0077] Unless otherwise specified as "substituted or unsubstituted", the groups described in the present invention may be substituted by substituents selected from the following groups: halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, hydroxyl, hydroxyl C1-C4 alkyl, OR 3 NR 3 R 4 、C(O)R 3 、C(O)OR 3 、C(O)NR 3 R 4 , SR 3 、S(O) m R 5、S(O)2NR 3 R 4 、OC(O)R 5 、OC(O)NR 3 R 4 、OS(O)2R 5 、OS(O)2NR 3 R 4 、N(R 6 )C(O)R 5 、N(R 6 )C(O)NR 3 R 4 、N(R 6 )S(O)2R 5 or N(R 6 )S(O)2NR 3 R 4 etc., wherein the R 3 , R 4 , R 5 , R 6 The definition of is the same as above, and m is 1 or 2.

[0078] The compounds of the present invention may contain one or more asymmetric centers and therefore appear in the form of racemates, racemic mixtures, single enantiomers, diastereomeric compounds and single diastereomers. The asymmetric centers that may exist depend on the properties of the various substituents on the molecule. Each such asymmetric center will independently produce two optical isomers, and all possible optical isomers and diastereomeric mixtures and pure or partially pure compounds are included within the scope of the present invention. The present invention includes all isomeric forms of the compounds, various crystalline forms, pharmaceutically, pesticide-acceptable salts, hydrates or solvates.

[0079] The term "pharmaceutically acceptable salt" refers to a salt formed by a compound of the present invention and an acid or base that is suitable for use as a drug. Pharmaceutically acceptable salts include inorganic salts and organic salts. A preferred class of salts is a salt formed by a compound of the present invention and an acid. Suitable acids for forming salts include, but are not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, benzenesulfonic acid, benzenesulfonic acid, and acidic amino acids such as aspartic acid and glutamic acid.

[0080] Inert solvents refer to various solvents that do not react with raw materials, including various linear, branched or cyclic alcohols, ethers or ketones, halogenated alkanes, 1,4-dioxane, acetonitrile, tetrahydrofuran, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and the like.

[0081] Pharmaceutical composition and method of administration:

[0082] Since the compound of the present invention has excellent inhibitory activity against chitinase, the compound of the present invention and its various crystal forms, pharmaceutically and pesticide-acceptable inorganic or organic salts, hydrates or solvates, and pharmaceutical compositions containing the compound of the present invention as the main active ingredient can be used to treat, prevent and alleviate field disasters caused by agricultural pests. According to the prior art, the compound of the present invention can be used to treat and prevent lepidopteran agricultural pests, and can also be used to treat specific pulmonary fibrosis, etc.

[0083] The compounds of formula (I), (II), (III), (IV), (V) of the present invention can be used in pharmaceutical compositions, which contain compounds of formula (I), (II), (III), (IV), (V) of the present invention within a safe and effective amount, antibiotics or pharmacologically acceptable salts thereof, and pharmacologically acceptable excipients or carriers. Wherein "safe and effective amount" means: the amount of the compound is sufficient to significantly improve the condition without causing serious side effects. Usually, the pharmaceutical composition contains 1-2000 mg of the compound of the present invention per dose, and more preferably, contains 5-200 mg of the compound of the present invention per dose. Preferably, the "one dose" is a capsule or tablet.

[0084] "Pharmaceutically acceptable carrier" refers to: one or more compatible solid or liquid fillers or gel substances, which are suitable for human use and must have sufficient purity and sufficiently low toxicity. "Compatibility" here means that the components in the composition can be mixed with the compounds of the present invention and with each other without significantly reducing the efficacy of the compounds. Some examples of carriers that are acceptable in pharmacy and pesticides include cellulose and its derivatives (such as sodium carboxymethyl cellulose, sodium ethyl cellulose, cellulose acetate, etc.), gelatin, talc, solid lubricants (such as stearic acid, magnesium stearate), calcium sulfate, vegetable oils (such as soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (such as propylene glycol, glycerol, mannitol, sorbitol, etc.), emulsifiers (such as ), wetting agents (such as sodium lauryl sulfate), colorants, flavoring agents, stabilizers, antioxidants, preservatives, pyrogen-free water, etc.

[0085] There is no particular limitation on the mode of administration of the compounds or pharmaceutical compositions of the present invention. Representative modes of administration include (but are not limited to): pharmaceutical portion: oral, intratumoral, rectal, parenteral (intravenous, intramuscular or subcutaneous), and topical administration; pesticide portion: spraying, dusting, soil treatment, injection, smearing, poison bait and seed dressing.

[0086] Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In these solid dosage forms, the active compound is mixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or with the following ingredients: (a) fillers or extenders, for example, starches, lactose, sucrose, glucose, mannitol and silicic acid; (b) binders, for example, hydroxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and acacia; (c) humectants, for example, glycerol; (d) disintegrants, for example, agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate; (e) solubilizers, for example, paraffin; (f) absorption accelerators, for example, quaternary ammonium compounds; (g) wetting agents, for example, cetyl alcohol and glyceryl monostearate; (h) adsorbents, for example, kaolin; and (i) lubricants, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In capsules, tablets and pills, the dosage forms may also contain buffering agents.

[0087] Solid dosage forms such as tablets, pills, capsules, pills and granules can be prepared using coatings and shell materials, such as enteric coatings and other materials known in the art. They may contain opacifying agents, and the release of the active compound or compounds in such compositions may be delayed in a certain part of the digestive tract. Examples of embedding components that can be used are polymeric substances and waxes. If necessary, the active compound can also be formed into microencapsulated form with one or more of the above-mentioned excipients.

[0088] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or tinctures. In addition to the active compound, the liquid dosage form may contain an inert diluent conventionally used in the art, such as water or other solvents, solubilizers and emulsifiers, for example, ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butylene glycol, dimethylformamide and oils, in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil or mixtures of these substances.

[0089] Besides these inert diluents, the composition may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

[0090] Suspensions, in addition to the active compounds, may contain suspending agents such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methanol and agar, or mixtures of these substances.

[0091] Compositions for parenteral injection may include physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous and nonaqueous carriers, diluents, solvents or excipients include water, ethanol, polyols and suitable mixtures thereof.

[0092] The dosage forms of the compounds of the present invention for topical administration include ointments, powders, patches, sprays and inhalants. The active ingredient is mixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants that may be required if necessary.

[0093] The compound of the present invention can be administered alone or in combination with other pharmaceutically or pesticide-acceptable compounds.

[0094] When using the pharmaceutical composition, a safe and effective amount of the compound of the present invention is applied to a mammal (such as a human) in need of treatment, wherein the dosage during administration is a pharmaceutically effective dosage. For a person weighing 60 kg, the daily dosage is usually 1 to 2000 mg, preferably 5 to 500 mg. Of course, the specific dosage should also take into account factors such as the route of administration and the health status of the patient, which are all within the skill of a skilled physician.

[0095] Example:

[0096] The following is a description with reference to the accompanying drawings: Figure 1 This is the inhibitory activity test chart of 08 on the chitinase OfChi-h of Asian corn borer. Figure 1 Showing 08 pairs of Ostrinia furnacalis chitinase OfChi-h K i 40.7nM; Figure 2 This is the inhibitory activity test diagram of 08 on human chitosan chitinase HsChit1. Figure 2 The K of human chitotriose chitinase HsChit1 was shown in Figure 08 i 12.1nM; Figure 3 This is a test chart of the inhibitory activity of 08 on the chitinase CeCht1 of Caenorhabditis elegans. Figure 3 08 pairs of K of the chitinase CeCht1 from Caenorhabditis elegans i 18.8nM; Figure 4 This is the inhibitory activity test chart of 08 against the acidic mammalian enzyme AMCase. Figure 4 Showing 08 pairs of K of the acidic mammalian enzyme AMCase i It is 64.1nM.

[0097] The aromatic fused ring imine compounds are prepared by the following method:

[0098]

[0099] The compound of formula I-VA and an equal amount of the compound of formula I-VB were reacted in an inert solvent at 110°C for 1 h. After the reaction was completed, a rotary evaporator was used to remove the inert solvent in the reaction solution, and column chromatography was performed using DCM:MeOH=25:1 to obtain the target compound.

[0100]

[0101] Take 360 ​​mg of 2-amino-N-benzyl-10-methyl-5-oxo-5H-pyrido[1,2-a:2',3'-d]pyrimidine-3-carboxamide and 120 mg of N,N-dimethylformamide dimethyl acetal (DMFDMA), add them into 5 ml of toluene, react at 110°C for 1 hour, and after TLC tracking, use a rotary evaporator to remove toluene in the reaction solution. Column chromatography DCM:MeOH=25:1 to obtain the target compound 08 as a yellow-green solid with a yield of 58.9%. 1 H NMR (400MHz, CDCl3) δ11.44(s,1H),9.55(s,1H),9.12(s,1H),8.83(d,J=6.9Hz,1H),8.58(d,J=1.9Hz,1H),8.47–8.35(m,1H),7.77(dt,J=8. 1,1.7Hz,1H),7.52(d,J=6.6Hz,1H),7.25–7.21(m,1H),6.87(t,J=7.0Hz,1H),3.31(s,3H),3.21(s,3H),2.66(s,3H),1.51–1.33(m,4H)ppm.

[0102] Other compounds can be synthesized by similar methods using corresponding raw materials according to the general synthesis reaction formula, and their NMR data are listed in the table below.

[0103] Table 1 Structures and NMR of aromatic fused ring imine compounds

[0104]

[0105]

[0106]

[0107]

[0108]

[0109]

[0110]

[0111]

[0112]

[0113] Last but not least of the genes OfChi-h, OfChtI, CeCht1, HsChit1, AmCase, AfChiB1, and SmChiA:

[0114] Structure, catalysis, and inhibition of Of Chi-h, the lepid optera-exclusive insectchitinase.Journal of Biological Chemistry, 292(6), 2080-2088.

[0115] Chen, L., Zhou, Y., Qu, M., Zhao, Y., & Yang, Q. (2014).Fully deacetylated chitooligosaccharides act as efficient glycoside hydrolase family 18 chitinase inhibitors.Journal of Biological Chemistry, 289(25), 17932-17940.

[0116] Chen, Q., Chen, W., Kumar, A., Jiang, X., Janezic, M., Zhang, K., & Yang, Q. ( 2021 ). Chemistry,69(11),3519-3526.

[0117] Schüttelkopf, AW, Andersen, OA, Rao, FV, Allwood, M., Rush, CL, Eggleston, IM, & van Aalten, DM (2011). Bisdionin C ARationally Designed, Submicromolar Inhibitor of Family 18 Chitinases. ACS medicinal chemistry letters, 2(6), 428-432.

[0118] Inhibition rate test method: The compound to be tested was dissolved in dimethyl sulfoxide (DMSO) to prepare a 10 mM stock solution.

[0119] Reaction system: The reaction system with a total volume of 100 μL contained an appropriate amount of chitinase, 20 μM MU-(GlcNAc)2, 2% (v / v) DMSO, 10 mM NaH2PO4, 10 mM Na2HPO4 (pH 6.0) and inhibitors of different concentrations.

[0120] At 30°C, the chitinase to be tested and the corresponding compound were first incubated for 10 min, then the substrate MU-(GlcNAc)2 was added, and the reaction was continued for 20 min. Then 100 μL of 0.5 M sodium carbonate solution was added to terminate the reaction. The fluorescence intensity was measured by a microplate reader (Tecan Infinite 200Pro) with an excitation wavelength of 360 nm and an emission wavelength of 440 nm. The fluorescence intensity of the experimental group was recorded as F E The fluorescence intensity of the negative control group without substrate is recorded as F N The fluorescence intensity of the positive control group without compound is recorded as F P The fluorescence intensity of the blank control is recorded as F B The inhibitory activity was calculated by the following formula.

[0121] Inhibition rate = [1-(F E -F N ) / (F P -F B )]×100%

[0122] Inhibition constant K i Determination of K value: The inhibitory activity of compounds at different concentrations was determined at three different substrate concentrations, with the reciprocal of the reaction rate as the ordinate and the compound concentration as the abscissa. The K value of the compound was calculated by the Dixon plots method. i value.

[0123] Table 2 Inhibitory activity of aromatic fused ring imine compounds on different chitinases at 1 μM concentration

[0124]

[0125]

[0126]

[0127]

[0128]

[0129]

[0130]

[0131]

Claims

1. An aromatic fused ring imine compound of the general formula (I), or an optical isomer, cis-trans isomer or a pharmaceutically or pesticide-acceptable salt or solvate thereof: in, Y is none, or a substituted or unsubstituted alkylene or alkylene-O- having 1 to 10 carbon atoms, wherein the alkylene is a straight chain or branched chain alkylene; M is selected from the group consisting of NH, O or S; R1 is located at One or more H or C1-C4 alkyl or halogen in the ring; R2, R3 are each independently selected from the group consisting of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, hydroxyl, amino, thiol, phosphino, nitro, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl; R4 is selected from the group consisting of hydrogen, halogen, hydroxy, nitro, amino, cyano, carbonyl, substituted or unsubstituted C2-C 12 Alkenyl, substituted or unsubstituted C2-C 12 Alkynyl, Carboxyl, substituted or unsubstituted C1-C 12 Alkyl or alkoxy, substituted or unsubstituted C1-C 12 Alkylamino, substituted or unsubstituted C3-C9 cycloalkyl, substituted or unsubstituted C 5-7 Cycloalkenyl, substituted or unsubstituted C2-C9 non-heteroaryl, substituted or unsubstituted 3-12 membered heterocyclic ring, substituted or unsubstituted C6-C 12 Aryl, substituted or unsubstituted C4-C 12 Heteroaryl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-membered or 6-membered heterocyclic group, or substituted or unsubstituted 8-12-membered heteroaromatic bicyclic group; Ring A is a substituted or unsubstituted 8-12 membered heteroaromatic bicyclic ring system, a substituted or unsubstituted 8-12 membered heteroaromatic tricyclic ring system, a substituted or unsubstituted 5-12 membered aromatic ring system, a substituted or unsubstituted 5-12 membered heterocyclic ring system, a substituted or unsubstituted 5-12 membered aromatic ring, a substituted or unsubstituted 5-12 membered heteroaromatic ring, or a substituted or unsubstituted 5-12 membered heterocyclic ring (including a fully or partially unsaturated heterocyclic ring); R5 is a substituent located at any one or more positions of the ring A, each independently, and R5 is selected from the following group: halogen, cyano, nitro, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 2-6 Alkenyl, substituted or unsubstituted C 2-6 Alkynyl, or substituted or unsubstituted C 3-7 Cycloalkyl, substituted or unsubstituted C 5-7 Cycloalkenyl, trimethylsilylethynyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, trimethylsilylethynyl, substituted or unsubstituted 5- or 6-membered heterocyclyl, substituted or unsubstituted 8- to 12-membered heteroaromatic bicyclic ring system, OR', Si(R')3, NR'R", C(O)R', C(O)OR', C(O)NR'R", SR', S(O) m R', S(O)2NR'R", OC(O)R', OC(O)NR'R", OS(O)2R', OS(O)2NR'R", N(R")C(O)R', NCH2R', N(R")C(O)NR'R", N(R")S(O)2R' or N(R')S(O)2NR'R"; Wherein, the substitution refers to that one or more hydrogen atoms on the group are replaced by a substituent selected from the following group: halogen, hydroxyl, nitro, amino, cyano, carbonyl, carboxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, hydroxyl C1-C6 alkyl, amino C1-C6 alkyl, carbonyl C1-C6 alkyl, OR', Si(R')3, NR'R", C(O)R', C(O)OR', C(O)NR'R", SR', S(O) m R', S(O)2NR'R", OC(O)R', OC(O)NR'R", OS(O)2R', OS(O)2NR'R", N(R")C(O)R' , NCH2R', N(R")C(O)NR'R", N(R")S(O)2R' or N(R')S(O)2NR'R", C3-C9 cycloalkyl, C6-C 12 Aryl, 3-12 membered heterocyclic ring, C4-C 12 heteroaryl; Wherein R' and R" are independently: H, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Halogenated cycloalkyl, C 2-6 Alkenyl, C 2-6 Halogenated alkenyl, C 2-6 Alkynyl, C 2-6 Haloalkynyl, substituted or unsubstituted C 3-7 Cycloalkyl, substituted or unsubstituted C 5-7 cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-membered or 6-membered saturated or unsaturated heterocyclic group, or substituted or unsubstituted 8-membered to 12-membered heteroaromatic bicyclic ring system; wherein the substituents on R' and R" are substituted by one or more groups selected from the group consisting of oxy (=O), halogen, cyano, nitro, C 1-6 Alkyl or cycloalkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Halogenated alkenyl, C 2-6 Alkynyl, C 2-6 Haloalkynyl, Hydroxyl, Hydroxyl C 1-4 alkyl.

2. The aromatic fused ring imine compound according to claim 1, or a pharmaceutically or pesticide-acceptable salt or solvate thereof, characterized in that: The compound has a structure as shown in formula (II), formula (III), formula (IV) or formula (V): wherein Y is none, or an unsubstituted straight chain alkylene or alkylene-O- having 1 to 10 carbon atoms; M is selected from the group consisting of NH, O or S; n is 0, 1, 2, 3; R1 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, ethyl, propyl, isopropyl, cyclopropyl, n-butyl or tert-butyl; R2, R3 are each independently selected from the following group: hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, isobutylhydroxy, amino, mercapto, phosphino, nitro, phenyl, benzyl, pyridyl, furyl, thienyl, methoxyphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1,2-dichlorophenyl, 1,3-dichlorophenyl, 1,4-dichlorophenyl, 1, 2-Dibromophenyl, 1,3-dibromophenyl, 1,4-dibromophenyl, 1,2-difluorophenyl, 1,3-difluorophenyl, 1,4-difluorophenyl, 1,2-dimethylphenyl, 1,3-dimethylphenyl, 1,4-dimethylphenyl, 1,2,4,5-tetrafluorophenyl, 1,2,3,4-tetrafluorophenyl, 1,2,3,5-tetrafluorophenyl, 1,2,4,5-tetrabromophenyl, 1,2,3,4-tetrabromophenyl, 1,2,3,5-tetrabromophenyl, 1,2,4,5-tetrachlorophenyl, 1,2,3,4-tetrachlorophenyl, 1,2,3,5-tetrachlorophenyl; R4, R5 are each independently selected from the following group: hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxy 2,3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperid ... 4-oxazine)phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

3. The aromatic fused ring imine compound according to claim 2, or a pharmaceutically or pesticide-acceptable salt or solvate thereof, characterized in that: The compound has the structure shown below: Y is none, or an unsubstituted straight chain alkylene group having 1, 2, or 3 carbon atoms; R4 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N-ethyl) substituent , N-(N-methyl-N-propyl) substituent, N-(N-methyl-N-butyl) substituent, N-(N-ethyl-N-propyl) substituent, N-(N-ethyl-N-butyl) substituent, N-(N-propyl-N-butyl) substituent, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxycyclohexyl , 2, 3 or 4-carboxycyclohexyl, 2, 3 or 4-cyanocyclohexyl, 2, 3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperazinyl) )phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

4. The aromatic fused-ring imine compound according to claim 2, or a pharmaceutically or pesticide-acceptable salt or solvate thereof, characterized in that: The compound has the structure shown below: R4, R5 are each independently selected from the following group: hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxy 2,3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperid ... 4-oxazine)phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

5. The compound according to claim 2, or a pharmaceutically or pesticide-acceptable salt or solvate thereof, characterized in that: The compound has the structure shown below: R2, R3 are each independently selected from the following group: hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, propenyl, allyl, butenyl, pentenyl, hexenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, isobutylhydroxy, amino, mercapto, phosphino, nitro, phenyl, benzyl, pyridyl, furyl, thienyl, methoxyphenyl, ethylphenyl, trifluoromethylphenyl, nitrophenyl, 1,2-dichlorophenyl, 1,3-dichlorophenyl, 1,4-dichlorophenyl, 1, 2-Dibromophenyl, 1,3-dibromophenyl, 1,4-dibromophenyl, 1,2-difluorophenyl, 1,3-difluorophenyl, 1,4-difluorophenyl, 1,2-dimethylphenyl, 1,3-dimethylphenyl, 1,4-dimethylphenyl, 1,2,4,5-tetrafluorophenyl, 1,2,3,4-tetrafluorophenyl, 1,2,3,5-tetrafluorophenyl, 1,2,4,5-tetrabromophenyl, 1,2,3,4-tetrabromophenyl, 1,2,3,5-tetrabromophenyl, 1,2,4,5-tetrachlorophenyl, 1,2,3,4-tetrachlorophenyl, 1,2,3,5-tetrachlorophenyl; R4, R5 are each independently selected from the following group: hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, nitro, cyano, carbonyl, amino, methoxy, ethoxy, propylamino, isopropyl, n-butoxy, tert-butoxy, cyclohexyloxy, N-(N,N-dimethyl) substituent, N-(N,N-diethyl) substituent, N-(N,N-dipropyl) substituent, N-(N,N-dibutyl) substituent, N-(N-methyl-N- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2, 3 or 4-methylcyclohexyl, 2, 3 or 4-ethylcyclohexyl, 2, 3 or 4-hydroxy 2,3 or 4-aminocyclohexyl, 2 or 3-tetrahydrofuranyl, 2 or 3-tetrahydrothienyl, N, 2 or 3-tetrahydropyrrolyl, 2, 3 or 4-tetrahydropyranyl, N, 2, 3 or 4-piperidinyl, N, 2 or 3-morpholinyl, N or 2-piperazinyl, N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperazinyl), N, 2 or 3-(N-benzylpiperidinyl), N, 2 or 3-(N-methylpiperid ... 4-oxazine)phenyl, 2,3 or 4-methylphenyl, 2,3 or 4-methoxyphenyl, 2,3 or 4-aminophenyl, 2,3 or 4-cyanophenyl, 2,3 or 4-carboxyphenyl, 2,3 or 4-nitrophenyl, 2,3 or 4-hydroxyphenyl, naphthyl, 2 or 3-furyl, 2 or 3-thienyl, N, 2 or 3-pyrrolyl, 2,3 or 4-pyridyl, N, 2 or 3-(N-morpholinyl)phenyl, indolyl.

6. The compound according to claim 1, or a pharmaceutically or pesticide-acceptable salt or solvate thereof, characterized in that: The compound part represents a compound having a structure of one of the following compounds:

7. Use of the aromatic fused-ring imine compound as claimed in any one of claims 1 to 6, or the optical isomers, cis-trans isomers or pharmaceutically or pesticide-acceptable salts or solvates thereof in the preparation of chitinase inhibitors.

8. The use of the compound according to claim 7, characterized in that The final concentration of the compound used in inhibiting the activity of family 18 chitinase is not less than 1 μM.

9. An aromatic fused-ring imine compound as claimed in any one of claims 1 to 6, or an optical isomer, cis-trans isomer or a pharmaceutically or pesticide-acceptable salt or solvate thereof, for use in controlling chitinase of agricultural pests or humans, fungi or bacteria.

10. A pharmaceutical composition comprising a therapeutically effective amount of an aromatic fused-ring imine compound as claimed in any one of claims 1 to 6, a pharmaceutically or pesticidely acceptable salt or a pharmaceutically or pesticidely acceptable solvate thereof as an active ingredient, and a pharmaceutically or pesticidely acceptable carrier.

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