Aromatic fused ring imine compound and its preparation method and application

Abstract

The present invention relates to an aromatic fused-ring imine compound and its preparation method and application. The aromatic fused-ring imine compound has a rigid planar structure and multiple hydrogen bond acceptors and donors. Its rigid planar structure can produce a π-π stacking effect with aromatic amino acid residues exposed to the solution in the chitinase binding pocket. Its hydrogen bond acceptors (such as carbonyl oxygen atoms) and hydrogen bond donors can produce direct or water-mediated hydrogen bonds with amino acids in the binding pocket, thereby producing an inhibitory effect on chitinase. Through evaluation and research on its inhibitory effect and selectivity, it is known that the aromatic fused-ring imine compound exhibits inhibitory activity on chitinases from Asian corn borer, humans, Caenorhabditis elegans, Brugia malayi, Aspergillus fumigatus, and Serratia marcescens, and has a wide range of application scenarios in the fields of biology and biochemistry.

Description

Technical Field

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

[0002] Chitin is a natural linear polysaccharide composed of N-acetyl-β-D-glucosamine (GlcNAc) as the basic unit, linked by β-1,4-glycosidic bonds. It is a key component of the insect exoskeleton and midgut peritrophic membrane, nematode eggshells, mollusk shells, and fungal cell walls. Its synthesis and degradation play an important role in the growth and development of these organisms. GH18 family chitinases are key enzymes for hydrolyzing chitin. Inhibition of chitinases involved in insect and nematode molting, such as the chitinases OfChi-h and OfChtI from the corn borer, the nematode chitinase CeCht1, and the Brugia malayi chitinase BmCht1, can prevent insects and nematodes from molting, inhibit their growth, fail to pupate, and eventually lead to their death. These chitinases are potential targets for pesticide development. The human body expresses two chitinases and numerous chitinase-like proteins. The expression of the human chitotriose chitinase HsChit1 is associated with pulmonary fibrosis and could serve as a potential therapeutic target for specific pulmonary fibrosis. Overexpression of the human acidic mammalian enzyme AMCase is associated with asthma and could serve as a potential therapeutic target for asthma. In recent years, significant progress has been made in the crystal structure resolution of various chitinases, providing a critical theoretical foundation for the rational design of small-molecule chitinase inhibitors for agricultural and medical applications.

[0003] Chitinase plays an important role in fungal infection, insect molting, nematode hatching, and human asthma and pulmonary fibrosis. Therefore, inhibitors of 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 present invention aims to provide an aromatic fused-ring imine compound, 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 on the ring;

[0011] R2, R3 are each independently selected from the group consisting of one or more 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, hydroxy, 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 heterocycle, 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, and R5 is selected from the following groups: 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 group consisting of 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', R" are independently: H, C 1-6 Alkyl, C 1-6 Halogenated alkyl, 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 Halogenated alkyl, C 2-6 Alkenyl, C 2-6 Halogenated alkenyl, C 2-6 Alkynyl, C 2-6 Haloalkynyl, hydroxyl, hydroxyl C 1-4 alkyl.

[0017] 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 group having 1 to 10 carbon atoms, or alkylene-O-;

[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 group consisting of 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 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- 4-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-hydroxy cyclohexyl, 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-benzylpiperidinyl), 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 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- 4-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-hydroxy cyclohexyl, 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-benzylpiperidinyl), 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 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- 4-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-hydroxy cyclohexyl, 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-benzylpiperidinyl), 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] Y is none, or an unsubstituted straight-chain alkylene group having 1, 2, or 3 carbon atoms;

[0035] 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-tetrahydrothiophenyl, 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.

[0036] In one embodiment of the present invention, the compound has the structure shown below:

[0037]

[0038] Y is none, or an unsubstituted straight-chain alkylene group having 1, 2, or 3 carbon atoms;

[0039] 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-tetrahydrothiophenyl, 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.

[0040] In one embodiment of the present invention, the compound has the structure shown below:

[0041]

[0042] R2, R3 are each independently selected from the group consisting of 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;

[0043] R4, R5 are each independently 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- 4-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-hydroxy cyclohexyl, 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-benzylpiperidinyl), 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.

[0044] In one embodiment of the present invention, Y, R1, R2, R3, R4, R5, M and ring A are each independently a group corresponding to a specific compound in the embodiment.

[0045] Furthermore, in the above, R5 is selected from hydrogen or methyl.

[0046] Furthermore, the R1 is located at A methyl group on the ring.

[0047] The present invention provides a class of preferred compounds of general formula (I), including but not limited to the structures of aromatic fused ring imine compounds 01-98 in Table 1.

[0048] A method for preparing an aromatic fused-ring imine compound, comprising the following steps:

[0049]

[0050] The compound of formula I-VA is reacted with the compound of formula I-VB in an inert solvent to obtain the compound of formula I-V.

[0051] An aromatic fused ring imine compound, or an optical isomer, cis-trans isomer or pharmaceutically and pesticide-acceptable salt or solvate thereof, 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.

[0052] Furthermore, 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.

[0053] An aromatic fused-ring imine derivative is based on the aromatic fused-ring imine compound. The derivative is an optical isomer, cis-trans isomer, pharmaceutically and pesticide-acceptable salt or solvate of the compound of formula (I), (II), (III), (IV) or (V). The salt or solvate is used in the chitinase of agricultural pests or humans, fungi or bacteria.

[0054] Furthermore, the agricultural pests are lepidopteran insects and nematodes.

[0055] Furthermore, the lepidopteran insects include wheat moth, pink bollworm, potato tuber moth, sweet potato moth, cotton brown-banded moth, soybean borer, pear borer, Asian corn borer, large bridge-building moth, cabbage butterfly, cotton bollworm, gypsy moth, jade butterfly, swallowtail butterfly, boat caterpillar, yellow-bellied moth, American white moth, grape hawkmoth and rice stem borer, etc.; the nematodes are Caenorhabditis elegans, Malayan filaria, root-knot nematode, cyst nematode, Heterodera nematode, seed-stub nematode, pine nematode, root-rot nematode and cone nematode.

[0056] 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.

[0057] Furthermore, the application in preventing and controlling agricultural pests is to delay 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 to prevent specific pulmonary fibrosis, asthma, antifungal infection and inhibit bacterial growth.

[0058] A pharmaceutical composition comprising a therapeutically effective amount of the aromatic fused-ring imine compound, a pharmaceutically and pesticidely acceptable salt or pharmaceutically and pesticidely acceptable solvate thereof as an active ingredient, and a pharmaceutically and pesticidely acceptable carrier.

[0059] Compared with the prior art, the present invention has the following advantages:

[0060] 1) The aromatic fused-ring imine compounds of the present invention have chitinase inhibitory activity (such as corn borer chitinase OfChi-h, Caenorhabditis elegans chitinase CeCht1, Brugia malayi chitinase BmCht1, and human chitotriose chitinase HsChit1, etc.). Evaluation studies on their inhibitory effects and selectivity have shown that the aromatic fused-ring imine compounds exhibit 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;

[0061] 2) The inhibitory activity data, including inhibition percentage and inhibition constant, showed that this class of structures exhibited broad inhibitory activity against OfChi-h, OfChtI, SmChiB, CeCht1, HsChit1, AmCase, and BmCht1;

[0062] 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 the chitinase OfChi-h of Asian corn borer was i The K for human HsChit1 is 40.7 nM. i The K of human AmCase is 12.1 nM. i The K of CeCht1 against the chitinase CeCht1 of Caenorhabditis elegans is 64.1 nM. i is 18.8nM;

[0063] 4) The aromatic fused-ring imine compounds of the present invention have a rigid planar structure and multiple hydrogen bond acceptors and donors. Their rigid planar structure can undergo π-π stacking with aromatic amino acid residues exposed to the solution in the chitinase binding pocket. Their 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

[0064] Figure 1 This is a test chart of the inhibitory activity of 08 on the chitinase OfChi-h of the Asian corn borer;

[0065] Figure 2 This is a test diagram of the inhibitory activity of 08 on human chitotriose chitinase HsChit1;

[0066] Figure 3 This is a test diagram of the inhibitory activity of 08 on the chitinase CeCht1 of Caenorhabditis elegans;

[0067] Figure 4 This is a test chart of the inhibitory activity of 08 against the acidic mammalian enzyme AMCase. DETAILED DESCRIPTION

[0068] The present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0069] Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood in the art to which this invention belongs.

[0070] The term "C 1-6 The term "alkyl" refers to a straight-chain or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or the like.

[0071] The term "C1-C6 alkoxy" refers to a substituent having a structure of "straight-chain or branched alkyl-oxy having 1 to 6 carbon atoms", such as ethoxy, propoxy, butoxy, or the like.

[0072] The term "C1-C6 alkylamino" refers to a substituent having a structure of a "straight-chain or branched alkylamino group having 1 to 6 carbon atoms", such as ethylamino, propylamino, dimethylamino, or similar groups.

[0073] The term "alkylene" refers to a group formed by losing a hydrogen atom from an alkyl group as described above, for example, -CH2-, -CH2-CH2-, or the like.

[0074] The term "C2-C 12 The term "alkenyl" refers to a linear or branched alkenyl group of olefins having 2 to 12 carbon atoms, including ethenyl, propenyl, n-alkenyl, or similar groups.

[0075] The term "C3-C9 cycloalkyl" refers to a cycloalkyl group having 3 to 9 carbon atoms, such as cyclopropane, cyclohexane, and the like.

[0076] 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 halogen atoms mentioned above, for example trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, or the like.

[0077] The term "ring" or "ring system" refers to a carbocyclic or heterocyclic ring.

[0078] The term "heterocycle" refers to an atom in which at least one of the atoms forming the heterocycle skeleton is not carbon but is nitrogen, oxygen or sulfur. Typically, the heterocycle comprises no more than 4 nitrogen atoms, no more than 2 oxygen atoms and / or no more than 2 sulfur atoms. Unless otherwise indicated, the heterocycle may be a saturated, partially unsaturated or fully unsaturated ring. In a preferred embodiment of the present invention, the heterocycle comprises 1-4 heteroatoms independently selected from N, S and O.

[0079] The term "ring system" refers to two or more rings fused together.

[0080] 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, furyl, 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 one or more heteroatoms selected from O, S, N or P, such as pyridyl, thienyl, or similar groups.

[0081] The term "heterocyclic ring system" refers to a ring system in which at least one ring of the ring system is a heterocycle.

[0082] The term "heteroaromatic ring system" refers to a system in which at least one ring in the ring system is aromatic.

[0083] 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.

[0084] The term "alkyl" refers to an alkane molecule with one hydrogen atom missing; the term "alkylene" refers to an alkane molecule with two hydrogen atoms missing. Similarly, "alkenylene," "alkynylene," "cycloalkylene," "cycloalkenylene," "phenylene," "naphthylene," "heterocyclylene," or "heteroaromatic bicyclic or tricyclic ring system" are similarly defined.

[0085] Unless otherwise specified as "substituted or unsubstituted", the groups of the present invention may be substituted by substituents selected from the group consisting of 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.

[0086] 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 center that may exist depends on the nature 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 purified compounds are included within the scope of the present invention. The present invention includes all isomeric forms of the compounds, various crystalline forms, pharmaceutically and pesticide-acceptable salts, hydrates or solvates.

[0087] The term "pharmaceutically acceptable salt" refers to a salt of a compound of the present invention formed with an acid or base that is suitable for pharmaceutical use. Pharmaceutically acceptable salts include inorganic salts and organic salts. A preferred class of salts are salts formed with a compound of the present invention and an acid. Suitable acids for salt formation include, but are not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as 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, phenylmethanesulfonic acid, and benzenesulfonic acid; and acidic amino acids such as aspartic acid and glutamic acid.

[0088] 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), etc.

[0089] Pharmaceutical composition and method of administration:

[0090] Because the compounds of the present invention have excellent chitinase inhibitory activity, the compounds of the present invention and their various crystalline forms, pharmaceutically and pesticide-acceptable inorganic or organic salts, hydrates, or solvates, as well as pharmaceutical compositions containing the compounds of the present invention as the primary active ingredient, can be used to treat, prevent, and alleviate field damage caused by agricultural pests. According to prior art, the compounds of the present invention can be used to treat and prevent lepidopteran agricultural pests and to treat specific pulmonary fibrosis, among other conditions.

[0091] The compounds of formula (I), (II), (III), (IV), and (V) of the present invention can be used in pharmaceutical compositions, which contain a safe and effective amount of the compounds of formula (I), (II), (III), (IV), and (V) of the present invention, an antibiotic or a pharmacologically acceptable salt thereof, and a pharmacologically acceptable excipient or carrier. "Safe and effective amount" means an amount of the compound sufficient to significantly improve the condition without causing serious side effects. Typically, the pharmaceutical composition contains 1-2000 mg of the compound of the present invention per dose, more preferably, 5-200 mg of the compound of the present invention per dose. Preferably, the "one dose" is one capsule or tablet.

[0092] "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 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, flavorings, stabilizers, antioxidants, preservatives, pyrogen-free water, etc.

[0093] There is no particular limitation on the mode of administration of the compound or pharmaceutical composition of the present invention. Representative modes of administration include (but are not limited to): pharmaceutical administration: oral, intratumoral, rectal, parenteral (intravenous, intramuscular or subcutaneous), and topical administration; pesticide administration: spraying, dusting, soil treatment, injection, smearing, poison baiting, and seed dressing.

[0094] 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 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 the case of capsules, tablets and pills, the dosage forms may also contain buffering agents.

[0095] Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells, such as enteric coatings and other materials known in the art. They may contain opacifying agents, and release of the active compound or compounds in such compositions can be delayed in a specific portion of the digestive tract. Examples of useful encapsulating components include polymeric substances and waxes. If desired, the active compound can also be microencapsulated with one or more of the above-mentioned excipients.

[0096] 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, isopropyl alcohol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butylene glycol, dimethylformamide, and oils, particularly cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, or mixtures thereof.

[0097] Besides such inert diluents, the composition may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

[0098] Suspensions, in addition to the active compounds, may contain suspending agents such as, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar, or mixtures of these substances.

[0099] 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.

[0100] Dosage forms for topical administration of the compounds of the present invention 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.

[0101] The compound of the present invention can be administered alone or in combination with other pharmaceutically or pesticide-acceptable compounds.

[0102] When using a pharmaceutical composition, a safe and effective amount of the compound of the present invention is administered to a mammal (e.g., a human) in need of treatment, wherein the dosage is a pharmaceutically effective dosage. For a 60 kg human, the daily dosage is generally 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 patient's health status, all of which are within the skill of a skilled physician.

[0103] Example:

[0104] The following is explained 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 Shows the K of 08 pairs of chitinase OfChi-h from Ostrinia furnacalis i 40.7nM; Figure 2 This is the inhibitory activity test chart of 08 on human chitotriose chitinase HsChit1. Figure 2 The K of 08 pairs of human chitotriose chitinase HsChit1 was shown. 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 of Caenorhabditis elegans i is 18.8nM; Figure 4 This is the inhibitory activity test chart of 08 against the acidic mammalian enzyme AMCase. Figure 4 Showing the K of 08 for the acidic mammalian enzyme AMCase i It is 64.1nM.

[0105] Aromatic fused ring imine compounds were prepared by the following method:

[0106]

[0107] 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 completion of the reaction, the inert solvent was removed from the reaction solution using a rotary evaporator, and the target compound was obtained by column chromatography using DCM:MeOH = 25:1.

[0108]

[0109] 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) were added to 5 ml of toluene and reacted at 110°C for 1 hour. After the reaction was completed, the toluene in the reaction solution was removed by rotary evaporation and column chromatography was performed using 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.

[0110] 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.

[0111] Table 1 Structures and NMR of aromatic fused-ring imine compounds

[0112]

[0113]

[0114]

[0115]

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122] Last but not least of the genes OfChi-h, OfChtI, CeCht1, HsChit1, AmCase, AfChiB1, and SmChiA:

[0123] Structure, catalysis, and inhibition of Of Chi-h, the lepid optera-exclusive insectchitinase.Journal of Biological Chemistry, 292(6), 2080-2088.

[0124] 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.

[0125] Chen, Q., Chen, W., Kumar, A., Jiang, X., Janezic, M., Zhang, K., & Yang, Q. ( 2021 ). Chemistry,69(11),3519-3526.

[0126] Schüttelkopf, AW, Andersen, OA, Rao, FV, Allwood, M., Rush, CL, Eggleston, IM, & van Aalten, DM (2011). Bisdionin CA Rationally Designed, Submicromolar Inhibitor of Family 18 Chitinases. ACS medicinal chemistry letters, 2(6), 428-432.

[0127] Inhibition rate test method: The test compound was dissolved in dimethyl sulfoxide (DMSO) to prepare a 10 mM stock solution.

[0128] 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 different concentrations of inhibitors.

[0129] At 30°C, the chitinase to be tested and the corresponding compound were first incubated for 10 minutes, and then the substrate MU-(GlcNAc)2 was added. After the reaction continued for 20 minutes, 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.

[0130] Inhibition rate = [1-(F E -F N ) / (F P -F B )]×100%

[0131] Inhibition constant K i Determination of K value: The inhibitory activity of different concentrations of compounds was determined at three different substrate concentrations. The reciprocal of the reaction rate was used as the ordinate and the compound concentration was used as the abscissa. The K value of the compound was calculated by Dixon plots. i value.

[0132] Table 2 Inhibitory activity of aromatic fused-ring imine compounds against different chitinases at a concentration of 1 μM

[0133]

[0134]

[0135]

[0136]

[0137]

[0138]

[0139]

[0140]

Claims

1. An aromatic fused-ring imine compound or a pharmaceutically or pesticide-acceptable salt thereof, characterized in that: The compound is one of the following compounds:

2. Use of the aromatic fused-ring imine compound according to claim 1 or a pharmaceutically and pesticide-acceptable salt thereof in the preparation of a chitinase inhibitor.

3. The use of the compound according to claim 2, characterized in that The final concentration of the compound used in inhibiting the activity of family 18 chitinase is not less than 1 μM.

4. The use of the compound according to claim 2, characterized in that The compound is selected from the following applications: application in delaying the growth and development of lepidopteran pests and hatching of nematode eggs; application in specific pulmonary fibrosis, asthma, antifungal infection and inhibition of bacterial growth.

5. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises a therapeutically effective amount of the aromatic fused ring imine compound or a pharmaceutically and pesticide-acceptable salt thereof as claimed in any one of claims 1 as an active ingredient, and a pharmaceutically and pesticide-acceptable carrier.

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