Imidazoquinoline or benzindazolone compounds and their preparation intermediates

Abstract

The present invention relates to imidazoquinoline or benzindazolone compounds, their pharmaceutically acceptable salts, hydrates, solvates, enantiomers, diastereoisomers, tautomers or prodrugs; their use in the prevention and treatment of inflammatory diseases; and intermediates for their preparation. By using the compounds of the present invention as substrates of NQO1 to activate the redox reaction of NQO1, the expression and activity of inflammatory cytokines can be inhibited, and thus they can be used for preventing or treating diseases related to NQO1 activity.

Description

Technical Field

[0001] The present invention relates to imidazoquinoline or benzindazolone compounds, their use for preventing or treating inflammatory diseases, and intermediates for their preparation. Background Art

[0002] Our body's immune system constructs various defense systems to protect the body from internal or external attacks. The functions of this immune system are divided into an immune response that increases immunity and immune tolerance that suppresses an excessive increase in the immune response. When these two immune functions are properly balanced, it is called immune homeostasis, which is very important for maintaining health.

[0003] However, due to various internal or external factors, the immune function may malfunction. When the immune response is stronger than immune tolerance, that is, when too many immune cells are activated, inflammatory diseases or autoimmune diseases may occur. On the contrary, when immune tolerance is stronger than the immune response, that is, when the immune system cannot function properly, infectious diseases or cancer are induced. Therefore, attempts are made to treat various immune-related diseases by maintaining the homeostasis of the immune system that balances immune response activation and suppression.

[0004] Ulcerative colitis, an inflammatory disease, is an inflammatory bowel disease that causes colon inflammation or intestinal ulcers due to genetic factors or an excessive immune response. Its common symptoms include mucus and blood in the stool, diarrhea, abdominal pain, weight loss, bleeding, etc. In most cases, inflammatory bowel disease shows repeated relapses and remissions and may lead to colon cancer or other complications. Although many studies have been conducted in the field of ulcerative colitis, a therapy that completely cures the disease has not been developed. Generally, anti-inflammatory drugs or adrenal corticosteroids are usually used, and immunosuppressants, steroids, antibiotics, etc. are used according to the patient's condition. It can be cured by surgery. However, surgery has significant complexity or side effects caused by sequelae, so drug treatment is recommended.

[0005] Autoimmune disease is a disease caused by an imbalance in which the immune response attacks healthy cells excessively. Representative examples include rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, atopic dermatitis, etc.

[0006] Our body has various immune suppressor cells that maintain immune homeostasis by suppressing autoimmune diseases or reducing an over-activated immune response. Among these cells, macrophages play an important role in innate immunity and are distributed in all tissues in the body in various phenotypes.

[0007] Macrophages usually protect our body by destroying external antigens through phagocytosis or secreting toxins. In addition, macrophages perform many different responses, such as wound healing and inflammatory responses. Macrophages can be divided into two typical phenotypes, M1 and M2, according to their pathological conditions. However, according to recent research trends, compared with this traditional dichotomous classification, macrophages have different phenotypes according to their origin, location, microenvironment, and disease state (Nature Immunology 2016(17), 34, Am J Physiol Gastrointest Liver Physiol 2016(311), G59). Proinflammatory macrophages with the M1 phenotype are activated by lipopolysaccharides (LPS) or tumor necrosis factor-α (TNF-α) and release IL-1β, IL-6, and TNF-α, etc. Their main metabolic pathway is glycolysis in the cytoplasm rather than mitochondrial metabolism. In addition, the main metabolic pathway of M2 macrophages is mitochondrial oxidative phosphorylation. They are activated by IL-4 or IL-10, etc., and play an important role in reducing inflammation and wound healing (Frontiers in immunology 2017, 61).

[0008] When the enzyme NAD(P)H quinone oxidoreductase 1 (NQO1) is activated in the body, NAD + and NAD + / NADH ratio increases, leading to mitochondrial activation, thus changing cellular metabolism from glycolysis to mitochondrial oxidative phosphorylation. This metabolic change induces the polarization of macrophages into an anti-inflammatory macrophage phenotype (M2 phenotype), resulting in the inhibition of the expression and activity of proinflammatory cytokines (Frontiers in immunology 2017, 289). Summary of the Invention

[0009] Technical Problem

[0010] The object of the present invention is to provide novel imidazoquinoline or benzindazolone compounds, or pharmaceutically acceptable salts, hydrates, solvates, enantiomers, diastereomers, tautomers or prodrugs thereof that exhibit a preventive or therapeutic effect on inflammatory diseases, as well as their preparation intermediates.

[0011] Technical Solution

[0012] The inventors of the present invention have confirmed through experiments that using the novel imidazoquinoline or benzindazolone compound as a substrate for NQO1 enables the redox reaction of NQO1 to proceed smoothly. Thus, by increasing the NAD + and NAD + / NADH ratio, leading to changes in cell metabolism caused by mitochondrial activation, and thus it can be used for the prevention or treatment of inflammatory diseases, thereby completing the present invention.

[0013] Accordingly, a first aspect of the present invention relates to a compound represented by the following Chemical Formula 1, or a pharmaceutically acceptable salt, hydrate, solvate, enantiomer, diastereomer, tautomer, or prodrug thereof.

[0014] Chemical formula 1

[0015]

[0016] In the formula,

[0017] R1 is selected from the group consisting of H, halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, nitro, cyano, -C(O)R5, -C(O)OR5, -C(O)NR6R7, and -NR6R7;

[0018] R2, R3, and R4 are each independently absent or selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5, and -S(O)(O)NR6R7;

[0019] Two of X1, X2, X3, and X4 are carbon (C) atoms, and the remaining two are nitrogen (N) atoms, provided that X1 and X3 cannot both be N and X2 and X4 cannot both be N;

[0020] is a single bond or a double bond, depending on R1, R2, R3, X1, X2, X3, and X4; and

[0021] --- is absent or is a single bond, depending on X1, X2, X3, and X4;

[0022] The above-mentioned alkyl group is a straight-chain, branched-chain or cyclic hydrocarbon, which may have a double bond or a triple bond in the hydrocarbon chain. When the alkyl group is substituted, its substituents are selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7 and -NR6R7;

[0023] When the above-mentioned heterocyclic group, aryl or heteroaryl is substituted, its substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7 and C substituted with one, two or three halogens 1-6 alkyl;

[0024] R5 is selected from the group consisting of H, C 1-6 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0025] R6 and R7 are each independently selected from the group consisting of H, C 1-6 alkyl, heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, or R6 and R7 combine together to form a heterocyclic group containing at least one nitrogen (N) atom in the ring and containing or not containing at least one additional heteroatom selected from N, O and S;

[0026] The above-mentioned aryl is a C 6-10 aromatic ring, the above-mentioned heterocyclic group is a 3- to 7-membered ring group having at least one heteroatom selected from N, O and S in the ring, and the above-mentioned heteroaryl is a 5- to 10-membered heteroaromatic ring having at least one heteroatom selected from N, O and S in the ring.

[0027] The second aspect of the present invention relates to a compound represented by the following Chemical Formula 2, or a salt, enantiomer, diastereomer or tautomer thereof, which is used as an intermediate for preparing the compound of the above Chemical Formula 1.

[0028] Chemical formula 2

[0029]

[0030] In the formula, R1, R2, R3, R4, X2, X3, X4, and---the same as defined in Chemical Formula 1, and R8 is a conventional hydroxyl protecting group well-known in the art of the present invention.

[0031] Effects of the Invention

[0032] According to the present invention, novel imidazoquinoline or benzisoxazolone compounds and their preparation intermediates are provided.

[0033] By measuring the value of the degree of reduction of cytochrome C, it was found that the compounds of the present invention act as effective substrates for NQO1. This enhanced redox reaction of NQO1 by the compounds of the present invention leads to changes in cell metabolism caused by mitochondrial activation by increasing the NAD + and NAD + / NADH ratio, thereby suppressing the expression and activity of inflammatory cytokines. Therefore, the compounds of the present invention are expected to be developed into drugs for preventing or treating inflammatory diseases. Detailed Description of the Invention

[0034] Term definition

[0035] Briefly describe the terms used in this specification.

[0036] The term "pharmaceutically acceptable salt" refers to a salt form of a compound that does not cause any severe irritation to the organism to which the compound is administered and does not destroy the biological activity and physical properties of the compound.

[0037] The terms "hydrate", "solvate", "prodrug", "tautomer", "enantiomer" and "diastereoisomer" also refer to compound forms that do not cause any severe irritation in the organism to which the compound is administered and do not destroy the biological activity and physical properties of the compound.

[0038] The "pharmaceutically acceptable salts" include acid addition salts formed by adding inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, etc., or organic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, fluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, salicylic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. In the case where a carboxylic acid group is present in the compound of Chemical Formula 1 above, examples of pharmaceutically acceptable carboxylates include metal salts or alkaline earth metal salts formed with lithium, sodium, potassium, calcium, magnesium, etc.; amino acid salts formed with lysine, arginine, guanidine, etc.; and organic salts formed with dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, diethanolamine, choline, trimethylamine, etc. The compounds of Chemical Formula 1 according to the present invention can be converted into their salts by conventional methods.

[0039] The term "hydrate" refers to the compound of the present invention or its salt containing a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.

[0040] The term "solvate" refers to the compound of the present invention or its salt containing a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. The solvent of the solvate can be any solvent that is volatile, non-toxic, and / or suitable for administration to humans.

[0041] The term "prodrug" refers to a substance that can be converted in vivo into the compound of Formula 1 of the present invention. In some cases, prodrugs are often used because they are easier to administer than their parent drugs. For example, bioactivity can be achieved by oral administration of a prodrug, while it is not possible for its parent drug. In addition, compared with the parent drug, the prodrug can have improved solubility in a pharmaceutical dosage form. For example, the prodrug can be in the form of an ester ("prodrug"), which can easily pass through cell membranes with poor water solubility and can be metabolically hydrolyzed into a carboxylic acid as the active form inside the cell where water solubility is beneficial. Another example of a prodrug can be a short peptide (polyamino acid) in which a peptide is linked to an acid group, which is metabolized to expose the active site.

[0042] The term "tautomer" refers to a structural isomer having the same chemical formula or molecular formula but different ways of connecting the constituent atoms. For example, its structure interconverts between two isomers, such as the keto-enol structure.

[0043] The term "enantiomer" or "diastereomer" refers to an isomer having the same chemical formula or molecular formula but arising from different spatial arrangements of atoms in the molecule. The term "enantiomer" refers to an isomer that does not overlap with its mirror image, such as the relationship between the right hand and the left hand. In addition, the term "diastereomer" refers to a stereoisomer that is not in a mirror-image relationship. All isomers and their mixtures are also included within the scope of the present invention.

[0044] The term "alkyl" refers to straight-chain, branched-chain, and cyclic aliphatic hydrocarbon groups, including "saturated alkyl" and "unsaturated alkyl" having at least one double bond or triple bond site in the chain.

[0045] The term "aryl" is a C 6-10 aromatic ring, the term "heterocyclic group" refers to a 3- to 7-membered ring having one or more heteroatoms selected from nitrogen (N), oxygen (O), and sulfur (O) atoms in the ring, and the term "heteroaryl" refers to a 5- or 10-membered heteroaromatic ring having one or more heteroatoms selected from nitrogen (N), oxygen (O), and sulfur (O) atoms in the ring.

[0046] Hereinafter, the present invention will be described in detail.

[0047] The first aspect of the present invention relates to a compound represented by the following chemical formula 1, or a pharmaceutically acceptable salt, hydrate, solvate, enantiomer, diastereoisomer, tautomer or prodrug thereof.

[0048] Chemical formula 1

[0049]

[0050] In the formula,

[0051] R1 is selected from the group consisting of H, halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, nitro, cyano, -C(O)R5, -C(O)OR5, -C(O)NR6R7 and -NR6R7;

[0052] R2, R3 and R4 are each independently absent, or selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5 and -S(O)(O)NR6R7;

[0053] Two of X1, X2, X3 and X4 are carbon (C) atoms, and the remaining two are nitrogen (N) atoms, provided that X1 and X3 cannot be N simultaneously and X2 and X4 cannot be N simultaneously;

[0054] is a single bond or a double bond, depending on R1, R2, R3, X1, X2, X3 and X4; and

[0055] --- is absent or is a single bond, depending on X1, X2, X3 and X4;

[0056] The above alkyl is a straight-chain, branched-chain or cyclic hydrocarbon group, which may have a double bond or a triple bond in the hydrocarbon chain. When the alkyl is substituted, the substituent is selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10in the group consisting of aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, and -NR6R7;

[0057] when the above-mentioned heterocyclic group, aryl, or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7, and C substituted with one, two, or three halogens 1-6 alkyl;

[0058] R5 is selected from the group consisting of H, C 1-6 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

[0059] R6 and R7 are each independently selected from the group consisting of H, C 1-6 alkyl, heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, or R6 and R7 combine together to form a heterocyclic group containing at least one nitrogen (N) atom in the ring and further containing or not containing at least one additional heteroatom selected from N, O, and S;

[0060] the above-mentioned aryl is a C 6-10 aromatic ring, the above-mentioned heterocyclic group is a 3- to 7-membered ring group having at least one heteroatom selected from N, O, and S in the ring, and the above-mentioned heteroaryl is a 5- to 10-membered heteroaromatic ring having at least one heteroatom selected from N, O, and S in the ring.

[0061] The compound of Formula 1 of the present invention includes a compound in which X2 and X3 are carbon (C) atoms and X1 and X4 are nitrogen (N) atoms. Herein, R1 is the same as defined above, R2 is selected from the group consisting of H, unsubstituted C 1-10 alkyl, and substituted or unsubstituted C 6-10 aryl, R3 is selected from the group consisting of H, -C(O)OR5, and -C(O)NR6R7, R4 does not exist, R5 is C 1-6 alkyl, and R6 and R7 are each independently H or C 1-6 alkyl.

[0062] The compound of Formula 1 of the present invention includes a compound in which X1 and X4 are carbon (C) atoms and X2 and X3 are nitrogen (N) atoms.

[0063] In the present invention, a first embodiment of the compound of Formula 1 in which X1 and X4 are carbon (C) atoms and X2 and X3 are nitrogen (N) atoms relates to a compound, wherein,

[0064] R2 is absent or is selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5, and -S(O)(O)NR6R7, wherein when the alkyl is substituted, the substituents are selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, and -NR6R7; and when the heterocyclic group, aryl, or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7, and C 1-6 alkyl substituted with one, two, or three halogens;

[0065] R3 is absent or is selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5, and -S(O)(O)NR6R7, wherein when the alkyl is substituted, the substituents are selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, and -NR6R7; and when the heterocyclic group, aryl, or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7, and C 1-6 alkyl substituted with one, two, or three halogens;

[0066] R4 is selected from the group consisting of H, halogen, substituted or unsubstituted C1-10 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5, and -S(O)(O)NR6R7, wherein when the alkyl is substituted, the substituents are selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, and -NR6R7, and when the heterocyclic group, aryl, or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7, and C 1-6 alkyl substituted with one, two, or three halogens;

[0067] R5 is H or C 1-6 alkyl, and R6 and R7 are each independently H or C 1-6 alkyl, or R6 and R7 combine together to form a heterocyclic group containing at least one nitrogen atom in the ring.

[0068] In the compound of the first embodiment,

[0069] R2 is absent, or is selected from the group consisting of H, unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, and substituted or unsubstituted heteroaryl, wherein when the heterocyclic group, aryl, or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, halogen, and -C(O)OR5, wherein R5 can be H or C 1-6 alkyl;

[0070] R3 is absent, or is optionally selected from C 1-10 alkyl, C 2-5 heterocyclic group, C 6-10 aryl, and heteroaryl;

[0071] R4 is selected from the group consisting of H, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10Selected from the group consisting of aryl, substituted or unsubstituted heteroaryl, wherein when the alkyl is substituted, the substituent is selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, heteroaryl and -NR6R7, and when the heterocyclic group, aryl or heteroaryl is substituted, the substituent is independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro and C substituted with one, two or three halogens 1-6 alkyl.

[0072] In the present invention, a second embodiment of a compound in which X1 and X4 of Chemical Formula 1 are carbon (C) atoms and X2 and X3 are nitrogen (N) atoms relates to a compound, wherein,

[0073] R2 is a substituted alkyl, and the substituents are independently substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, or substituted or unsubstituted heteroaryl, and when the heterocyclic group, aryl or heteroaryl is substituted, the substituent is independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy and halogen;

[0074] R3 is absent or is selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5 and -S(O)(O)NR6R7, wherein when the alkyl is substituted, the substituent is selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7 and -NR6R7, and when the heterocyclic group, aryl or heteroaryl is substituted, the substituent is independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7 and C substituted with one, two or three halogens 1-6in the group consisting of alkyl groups;

[0075] R4 is selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5 and -S(O)(O)NR6R7, wherein when the alkyl group is substituted, the substituent is selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, heteroaryl, -C(O)R5, -C(O)OR5, -C(O)NR6R7 and -NR6R7. When the heterocyclic group, aryl or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7 and C 1-6 alkyl substituted with one, two or three halogens;

[0076] R5 is H or C 1-6 alkyl, and R6 and R7 are each independently H or C 1-6 alkyl, or R6 and R7 combine together to form a heterocyclic group containing at least one nitrogen atom in the ring.

[0077] In the compounds of the second embodiment, R2 and R3 can each be a substituted alkyl group, and the substituents are independently substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl or substituted or unsubstituted heteroaryl, wherein when the heterocyclic group, aryl or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy and halogen; R4 can be H or C 1-10 alkyl.

[0078] In the present invention, a third embodiment of the compound in which X1 and X4 of Formula 1 are carbon (C) atoms and X2 and X3 are nitrogen (N) atoms relates to a compound, wherein,

[0079] R2 is absent or selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-10 alkenyl, substituted or unsubstituted C 2-10 alkynyl, substituted or unsubstituted C2-5 a heterocyclic group, a substituted or unsubstituted C 6-10 selected from the group consisting of an aryl group, a substituted or unsubstituted heteroaryl group, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5, and -S(O)(O)NR6R7, wherein when the alkyl group is substituted, the substituents are selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, a substituted or unsubstituted C 2-5 heterocyclic group, a substituted or unsubstituted C 6-10 selected from the group consisting of an aryl group, a heteroaryl group, -C(O)R5, -C(O)OR5, -C(O)NR6R7, and -NR6R7, and when the heterocyclic group, aryl group, or heteroaryl group is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7, and a C 1-6 alkyl group substituted with one, two, or three halogens;

[0080] R3 is -S(O)(O)R5 or -S(O)(O)NR6R7;

[0081] R4 is selected from the group consisting of H, halogen, a substituted or unsubstituted C 1-10 alkyl, a substituted or unsubstituted C 2-5 heterocyclic group, a substituted or unsubstituted C 6-10 selected from the group consisting of an aryl group, a substituted or unsubstituted heteroaryl group, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -S(O)(O)R5, and -S(O)(O)NR6R7, wherein when the alkyl group is substituted, the substituents are selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, a substituted or unsubstituted C 2-5 heterocyclic group, a substituted or unsubstituted C 6-10 selected from the group consisting of an aryl group, a heteroaryl group, -C(O)R5, -C(O)OR5, -C(O)NR6R7, and -NR6R7, and when the heterocyclic group, aryl group, or heteroaryl group is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)R5, -C(O)OR5, -C(O)NR6R7, -NR6R7, and a C 1-6 alkyl group substituted with one, two, or three halogens;

[0082] R5 is selected from the group consisting of H, C 1-6 alkyl, a substituted or unsubstituted C 2-5 selected from the group consisting of a heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group; and

[0083] R6 and R7 are each independently selected from the group consisting of H, C 1-6 alkyl, heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, or R6 and R7 combine together to form a heterocyclic group containing at least one nitrogen (N) atom in the ring and further containing or not containing at least one additional heteroatom selected from N, O, and S, wherein when the heterocyclic group, aryl, or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, nitro, cyano, -C(O)OR9, and C substituted with one, two, or three halogens 1-6 alkyl, wherein R9 is H or C 1-6 alkyl.

[0084] In the compound of the third embodiment,

[0085] R2 is absent; R3 is -S(O)(O)R5; R4 is selected from the group consisting of H, halogen, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, and substituted or unsubstituted heteroaryl; R5 is optionally selected from the group consisting of H, C 1-6 alkyl, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

[0086] wherein when the alkyl is substituted, the substituents are selected from the group consisting of halogen, C 1-6 alkoxy, cyano, nitro, substituted or unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted C 6-10 aryl, and heteroaryl, and when the heterocyclic group, aryl, or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, nitro, cyano, -C(O)OR9, and C substituted with one, two, or three halogens 1-6 alkyl, wherein R9 can be H or C 1-6 alkyl.

[0087] In the present invention, the above-mentioned halogen is at least one selected from fluorine, chlorine, bromine and iodine. The above-mentioned aryl is preferably phenyl or naphthyl, and the above-mentioned heteroaryl is preferably a 5- to 10-membered heteroaromatic ring having at least one heteroatom selected from N, O and S in the ring, and examples thereof may include pyridyl, pyridazinyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, furyl, etc., but are not limited thereto. The above-mentioned heterocyclic group is a 3- to 7-membered heterocyclic group having at least one heteroatom selected from N, O and S in the ring, and examples thereof may include aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, etc., but are not limited thereto.

[0088] The compounds of Formula 1 of the present invention may include the following Compounds 1 to 70:

[0089] Compound 1: 1-Phenylimidazo[1,2-a]quinoline-4,5-dione;

[0090] Compound 2: 1-(4-Fluorophenyl)imidazo[1,2-a]quinoline-4,5-dione;

[0091] Compound 3: 1-Isopropylimidazo[1,2-a]quinoline-4,5-dione;

[0092] Compound 4: 1-(4-(Trifluoromethyl)phenyl)imidazo[1,2-a]quinoline-4,5-dione;

[0093] Compound 5: Ethyl 4,5-dioxo-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxylate;

[0094] Compound 6: Ethyl 4,5-dioxo-1-phenyl-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxylate;

[0095] Compound 7: N,N-Dimethyl-4,5-dioxo-1-phenyl-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxamide;

[0096] Compound 8: N-Methyl-4,5-dioxo-1-phenyl-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxamide;

[0097] Compound 9: 3-Methyl-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0098] Compound 10: 3-Isopropyl-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0099] Compound 11: 3-Heptyl-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0100] Compound 12: 3-Phenylethyl-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0101] Compound 13: 1,3-Diphenyl-1H-benzo[g]indazole-4,5-dione;

[0102] Compound 14: 3-(4-Fluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0103] Compound 15: 3-(3,4-Difluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0104] Compound 16: 3-(Bromomethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0105] Compound 17: 3-((Dimethylamino)methyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0106] Compound 18: 3-(Methoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0107] Compound 21: 3-(Isopropoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0108] Compound 20: 1-Isopropyl-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0109] Compound 21: 2-Isopropyl-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0110] Compound 22: 1,3-Dimethyl-1H-benzo[g]indazole-4,5-dione;

[0111] Compound 23: 2,3-Dimethyl-2H-benzo[g]indazole-4,5-dione;

[0112] Compound 24: 3-((1H-Imidazol-1-yl)methyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0113] Compound 25: 1-(4-Fluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0114] Compound 26: 1-(4-Chlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0115] Compound 27: 1-(3,5-Difluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0116] Compound 28: 1-(2,4-dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0117] Compound 29: 3-methyl-1-p-tolyl-1H-benzo[g]indazole-4,5-dione;

[0118] Compound 30: 3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole-4,5-dione;

[0119] Compound 31: 3-methyl-1-(pyridin-3-yl)-1H-benzo[g]indazole-4,5-dione;

[0120] Compound 32: 1-(2,4-difluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0121] Compound 33: 1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0122] Compound 34: 1-phenyl-3-(trifluoromethyl)-1H-benzo[g]indazole-4,5-dione;

[0123] Compound 35: 7-fluoro-3-methyl-1-phenyl-1H-benzo[g]indazole-4,5-dione;

[0124] Compound 36: 1-(3,5-dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0125] Compound 37: 4-(3-methyl-4,5-dioxo-4,5-dihydro-1H-benzo[g]indazol-1-yl)benzoic acid;

[0126] Compound 38: 3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole-4,5-dione;

[0127] Compound 39: 1-(5-chloropyridin-3-yl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0128] Compound 40: 3-methyl-1-(thiazol-2-yl)-1H-benzo[g]indazole-4,5-dione;

[0129] Compound 41: 3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazole-4,5-dione;

[0130] Compound 42: 3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazole-4,5-dione;

[0131] Compound 43: 3-Methyl-1H-benzo[g]indazole-4,5-dione;

[0132] Compound 44: 3-Methyl-2-(phenylsulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0133] Compound 45: 3-Methyl-2-(4-fluorophenylsulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0134] Compound 46: 2-(2-Chlorophenylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0135] Compound 47: 2-(3-Chlorophenylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0136] Compound 48: 3-Methyl-2-(pyridin-3-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0137] Compound 49: 2-(4-Chlorophenylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0138] Compound 50: 3-Methyl-2-(tosyl)-2H-benzo[g]indazole-4,5-dione;

[0139] Compound 51: 2-(4-Methoxyphenylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0140] Compound 52: Methyl 4-(3-methyl-4,5-dioxo-4,5-dihydro-2H-benzo[g]indazol-2-ylsulfonyl)benzoate;

[0141] Compound 53: 2-(Cyclopropylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0142] Compound 54: 2-(Cyclopentylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0143] Compound 55: 4-(3-Methyl-4,5-dioxo-4,5-dihydro-2H-benzo[g]indazol-2-ylsulfonyl)benzonitrile;

[0144] Compound 56: 3-Methyl-2-(4-nitrophenylsulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0145] Compound 57: 3-Methyl-2-(4-(trifluoromethyl)phenylsulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0146] Compound 58: 2-(3,4-difluorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0147] Compound 59: 2-(2,4-difluorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0148] Compound 60: 3-methyl-2-(quinolin-8-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0149] Compound 61: 3-methyl-2-(1-methyl-1H-imidazol-2-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0150] Compound 62: 3-methyl-2-(morpholinesulfonyl)-2H-benzo[g]indazole-4,5-dione;

[0151] Compound 63: 1-benzyl-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0152] Compound 64: 3-methyl-1-phenethyl-1H-benzo[g]indazole-4,5-dione;

[0153] Compound 65: 1-(4-fluorophenethyl)-3-methyl-1H-benzo[g]indazole-4,5-dione;

[0154] Compound 66: 2-(4-fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione;

[0155] Compound 67: 3-methyl-1-(3-phenylpropyl)-1H-benzo[g]indazole-4,5-dione;

[0156] Compound 68: 3-methyl-1-(4-methylphenethyl)-1H-benzo[g]indazole-4,5-dione;

[0157] Compound 69: 3-methyl-2-(4-methylphenethyl)-2H-benzo[g]indazole-4,5-dione; and

[0158] Compound 70: 2-(2-fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione.

[0159] A second aspect of the present invention relates to a compound represented by the following Chemical Formula 2, or a salt, enantiomer, diastereomer or tautomer thereof, which is an intermediate for preparing the compound of Chemical Formula 1 above:

[0160] Chemical formula 2

[0161]

[0162] In the formula, R1, R2, R3, R4, X2, X3, X4, and --- are the same as defined in Chemical Formula 1, and R8 is a conventional hydroxyl protecting group well-known in the field of the present invention. Examples of the above protecting groups may include C 1-6 alkyl; C 6-10 aryl-substituted C 1-6 alkyl, such as benzyl, trityl, methoxybenzyl, etc.; C 1-6 alkoxy-substituted C 1-6 alkyl, such as methoxymethyl, methoxyethoxymethyl, etc.; carbonyl, such as acetyl, pivaloyl, etc.; heterocyclic group, such as tetrahydropyranyl, tetrahydrofuryl, etc.; C 1-6 alkyl-substituted silyl, such as trimethylsilyl, triisopropylsilyl, t-butylmethylsilyl, etc.; C 1-6 alkylcarbonyl, such as acetyl, pivaloyl, etc., but not limited thereto.

[0163] The compounds of the above Chemical Formula 2 are selected from the group consisting of the following compound combinations.

[0164] 5-(Benzyloxy)-1-phenylimidazo[1,2-a]quinoline;

[0165] Ethyl 5-(benzyloxy)imidazo[1,2-a]quinoline-2-carboxylate;

[0166] 5-(Benzyloxy)-1-(4-fluorophenyl)imidazo[1,2-a]quinoline;

[0167] 5-(Benzyloxy)-1-isopropylimidazo[1,2-a]quinoline;

[0168] 5-(Benzyloxy)-1-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoline;

[0169] 5-Methoxy-3-methyl-1-phenyl-1H-benzo[g]indazole;

[0170] (5-Methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)methanol;

[0171] 3-(Bromomethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole;

[0172] 5-Methoxy-3-methyl-1H-benzo[g]indazole;

[0173] 1-(4-Fluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole;

[0174] 1-(4-chlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole;

[0175] 1-(3,5-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole;

[0176] 1-(2,4-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole;

[0177] 5-methoxy-3-methyl-1-p-tolyl-1H-benzo[g]indazole;

[0178] 5-methoxy-3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole;

[0179] 5-methoxy-3-methyl-1-(pyridin-3-yl)-1H-benzo[g]indazole;

[0180] 1-(2,4-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole;

[0181] 5-methoxy-1-phenyl-1H-benzo[g]indazole;

[0182] 5-methoxy-1-phenyl-3-(trifluoromethyl)-1H-benzo[g]indazole;

[0183] 7-fluoro-5-methoxy-3-methyl-1-phenyl-1H-benzo[g]indazole;

[0184] 1-(3,5-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole;

[0185] Methyl 4-(5-methoxy-3-methyl-1H-benzo[g]indazol-1-yl)benzoate;

[0186] 5-methoxy-3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole; and

[0187] 1-(5-chloropyridin-3-yl)-5-methoxy-3-methyl-1H-benzo[g]indazole.

[0188] The third aspect of the present invention relates to a pharmaceutical composition comprising a compound represented by the above chemical formula 1, or a pharmaceutically acceptable salt, hydrate, solvate, enantiomer, diastereoisomer, tautomer or prodrug thereof as an active ingredient.

[0189] The above pharmaceutical composition may further comprise one or more selected from the group consisting of carriers, excipients and diluents well known in the art of pharmaceutical compositions.

[0190] The compound of Formula 1 of the present invention can be used as a substrate of NQO1 to inhibit the expression and activity of inflammatory cytokines. Therefore, the above-mentioned pharmaceutical composition can be used for preventing or treating diseases related to NQO1 activity.

[0191] Example

[0192] Hereinafter, the present invention will be described in more detail by way of examples. These examples are only for illustrating the present invention in more detail, and the scope of the present invention is not limited to these examples.

[0193] Preparation Example 1: Synthesis of Intermediate 1 (4-(Benzyloxy)quinolin-2-amine)

[0194] 2-Amino-4-hydroxyquinoline hydrate (5 mmol) and sodium hydride (10 mmol) were dissolved in dimethylformamide (20 mL) at 0 °C. After stirring for 5 minutes, the temperature was raised to room temperature, benzyl bromide (5.5 mmol) was added, and the reaction was carried out for 17 hours. An ethyl acetate:n-hexane 1:1 mixture was slowly added to the reaction solution and stirred. The resulting solid was filtered, and the filtrate was washed with saturated aqueous sodium bicarbonate solution and dried to obtain the title compound without further purification.

[0195] Yield: 44%, white solid.

[0196] 1 H NMR (300 MHz, DMSO-d6) δ: 7.85 - 7.82 (d, J = 8.0 Hz, 1H), 7.53 - 7.51 (m, 2H), 7.46 - 7.33 (m, 5H), 7.11 - 7.06 (m, 1H), 6.30 (br s, 2H), 6.28 (s, 1H), 5.23 (s, 2H).

[0197] Preparation Example 2: Synthesis of Intermediate 2 (Ethyl 5-(benzyloxy)imidazo[1,2-a]quinoline-2-carboxylate)

[0198] (1) Synthesis of 1-(4-(Benzyloxy)-2-diaminoquinolin-1(2H)-yl)penta-2,3-dienebromide

[0199] 4-(Benzyloxy)quinolin-2-amine (1 mmol, Intermediate 1) was dissolved in THF (10 mL) at room temperature, and ethyl 3-bromo-2-oxopropionate (2 mmol) was added, followed by reaction for 12 hours. After the reaction was complete, the resulting solid was washed with THF and filtered. The solid title compound was obtained without further purification.

[0200] (2) Synthesis of Intermediate 2 (Ethyl 5-(benzyloxy)imidazo[1,2-a]quinoline-2-carboxylate)

[0201] Dissolve the previously prepared 1-(4-(benzyloxy)-2-diaminoquinolin-1(2H)-yl)penta-2,3-dienebromide (1 mmol) in ethanol (10 mL), and react under heating and reflux conditions for 10 hours. After the reaction is complete, concentrate the solvent under reduced pressure and purify by column chromatography.

[0202] Yield: 57%, light yellow solid.

[0203] 1 H NMR (300 MHz, DMSO-d6) δ: 8.54 (s, 1H), 8.29 - 8.26 (m, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.73 - 7.67 (m, 1H), 7.55 - 7.39 (m, 6H), 6.88 (s, 1H), 5.27 (s, 2H), 4.46 (q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H).

[0204] Preparation Example 3: Synthesis of Intermediate 3 (1-Bromo-4-methoxy-2-naphthoic acid)

[0205] (1) Synthesis of Methyl 1-hydroxy-3-naphthoate

[0206] Dissolve benzaldehyde (282 mmol) and dimethyl succinate (310.2 mmol) in methanol (100 mL). After slowly adding 25% sodium methoxide solution (366.6 mmol), raise the temperature and react under reflux conditions for 12 hours. After the reaction is complete, add 3M HCl to acidify the reaction solution to pH 1, extract with methylene chloride, dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Do not further purify the obtained mixture, concentrate under reduced pressure, redissolve in THF (80 mL), stir at room temperature, add trifluoroacetic anhydride (282 mmol), raise the temperature and react under reflux conditions. After the reaction is terminated, cool the reaction solution to room temperature and neutralize with saturated aqueous sodium carbonate solution at 0 °C. Extract the reaction mixture with ethyl acetate, dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure. Purify the obtained compound by column chromatography.

[0207] Yield: 30%, light yellow solid.

[0208] 11H NMR (300 MHz, CDCl3) δ: 8.26 - 8.21 (m, 2H), 7.93 - 7.90 (m, 1H), 7.63 - 7.51 (m, 3H), 5.95 (s, 1H), 3.98 (s, 3H).

[0209] (2) Synthesis of methyl 4 - methoxy - 2 - naphthoate

[0210] Methyl 1 - hydroxy - 3 - naphthoate (4.54 mmol) and potassium carbonate (9.08 mmol) were dissolved in dimethylformamide (15 mL). After adding methyl iodide (9.54 mmol), the mixture was stirred at room temperature for 2 hours. After the reaction was complete, water was added to terminate the reaction, and the mixture was extracted with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained compound was used in the next reaction without further purification.

[0211] (3) Synthesis of methyl 1 - bromo - 4 - methoxy - 2 - naphthoate

[0212] Methyl 1 - hydroxy - 3 - naphthoate (24.7 mmol) was dissolved in acetonitrile (60 mL). N - Bromosuccinimide (26 mmol) was added to the reaction solution, and the temperature was raised, and the reaction was carried out under reflux conditions. After the reaction was complete, the reaction solution was concentrated under reduced pressure. The obtained solid was purified by column chromatography.

[0213] Yield: 90%, light yellow solid.

[0214] 1 1H NMR (300 MHz, CDCl3) δ: 8.42 (d, J = 8.3 Hz, 1H), 8.30 (d, J = 7.7 Hz, 1H), 7.70 - 7.59 (m, 2H), 7.05 (s, 1H), 4.05 (s, 3H), 4.03 (s, 3H).

[0215] (4) Synthesis of Intermediate 3 (1 - bromo - 4 - methoxy - 2 - naphthoic acid)

[0216] Methyl 1 - bromo - 4 - methoxy - 2 - naphthoate (17.8 mmol) was dissolved in a mixture of THF, methanol, and water (1:1:1 v / v). After adding potassium hydroxide (53.4 mmol), the temperature was raised, and the mixture was stirred under reflux conditions for 3 hours. After the reaction solution was cooled to room temperature, 1 M aqueous hydrochloric acid was added to acidify the solution. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The title compound was obtained by recrystallization from methylene chloride.

[0217] Yield: 99%, white solid.

[0218] 11H NMR (300 MHz, CDCl3) δ: 8.48 (d, J = 7.9 Hz, 1H), 8.31 (d, J = 8.0 Hz, 1H), 7.72 - 7.60 (m, 2H), 7.25 (s, 1H), 4.06 (s, 3H).

[0219] Preparation Example 4: Synthesis of Intermediate 4 (1-(1-Bromo-4-methoxynaphthalen-2-yl)ethan-1-one)

[0220] (1) Synthesis of 1-Bromo-N,4-dimethoxy-N-methyl-2-naphthamide

[0221] After suspending 1-bromo-4-methoxy-2-naphthoic acid (10 mmol, Intermediate 3) in 100 ml of methylene chloride, N,O-dimethylhydroxylamine hydrochloride (11 mmol) was added. Triethylamine (40 mmol) was added to the reaction solution, and after stirring for 5 minutes at room temperature, bis(2-oxo-3-oxazolidinyl)phosphinic chloride (11 mmol) was added, and the mixture was stirred for 12 hours at room temperature. After the reaction was terminated, 100 ml of 1 M aqueous hydrochloric acid solution was added, and the mixture was stirred for 10 minutes and then extracted with methylene chloride. The extract was washed with saturated aqueous sodium bicarbonate solution and distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The product was used in the next reaction without further purification.

[0222] (2) Synthesis of Intermediate 4 (1-(1-Bromo-4-methoxynaphthalen-2-yl)ethan-1-one)

[0223] 1-Bromo-N,4-dimethoxy-N-methyl-2-naphthamide (10 mmol) was dissolved in 100 ml of THF. After cooling the temperature of the reaction solution to 0 °C, methylmagnesium bromide (30 mmol) was slowly added to the reaction solution and stirred for 10 minutes. After raising the temperature of the reaction solution to room temperature, it was stirred for 5 hours. After the reaction was terminated, the reaction solution was cooled to 0 °C, and then 100 ml of 1 M aqueous NH4Cl solution was slowly added. After stirring for 10 minutes, the organic layer was separated. The aqueous layer was extracted with ethyl acetate, the organic layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography.

[0224] Yield: 80%, white solid.

[0225] 1 1H NMR (300 MHz, CDCl3) δ: 8.33 - 8.27 (m, 2H), 7.70 - 7.59 (m, 2H), 6.73 (s, 1H), 4.02 (s, 3H), 2.74 (s, 3H).

[0226] Preparation Example 5: Synthesis of Intermediate 5 (5-Methoxy-3-methyl-1-phenyl-1H-benzo[g]indazole)

[0227] (1) Synthesis of 1-(1-(1-Bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-phenylhydrazine

[0228] 1-(1-Bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4), phenylhydrazine (10.8 mmol) and p-toluenesulfonic acid monohydrate (1.4 mmol) were dissolved in ethanol (45 ml). The temperature was raised and the reaction was carried out under reflux for 3 hours. After the reaction was complete, the reaction solution was cooled to 0 °C and stirred for 3 hours. The resulting solid was filtered, washed with cold ethanol, and dried under vacuum to obtain a white solid, which was used in the next reaction without further purification.

[0229] (2) Synthesis of Intermediate 5 (5-Methoxy-3-methyl-1-phenyl-1H-benzo[g]indazole)

[0230] 1-(1-(1-Bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-phenylhydrazine (5 mmol) was dissolved in 1,4-dioxane (12.5 mL). Cuprous iodide (5 mol%), trans-4-hydroxy-L-proline (5 mol%) and potassium hydroxide (10 mmol) were added to the reaction solution, and the reaction was carried out under reflux for 10 hours. After the reaction solution was cooled to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography.

[0231] Yield: 35%, light brown solid.

[0232] 1 H NMR (300 MHz, DMSO-d6) δ: 8.30 (m, 1H), 7.67 - 7.39 (m, 8H), 7.18 (s, 1H), 4.05 (s, 3H), 2.58 (s, 3H).

[0233] Preparation Example 6: Synthesis of Intermediate 6 ((5-Methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)methanol)

[0234] (1) Synthesis of 1-(1-Bromo-4-methoxynaphthalen-2-yl)-2-hydroxyethan-1-one

[0235] 1-(1-Bromo-4-methoxynaphthalen-2-yl)ethan-1-one (62.44 mmol, Intermediate 4), KOH (343.42 mmol), and PhI(OAc)2 (78.05 mmol) were dissolved in methanol (400 ml). After reacting for 5 h, methanol was removed under reduced pressure. After adding water to the reaction solution, it was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in methanol, 2N HCl was added, and it was stirred overnight. After completion of the reaction, methanol was removed, the aqueous layer was extracted with ethyl acetate, the organic layer was washed with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, and then purified by column chromatography.

[0236] Yield: 60%, white solid.

[0237] 1 H NMR (300 MHz, CDCl3) δ: 8.35 - 8.29 (m, 2H), 7.72 - 7.60 (m, 2H), 6.79 (s, 1H), 4.89 (d, J = 4.7 Hz, 2H), 4.03 (s, 3H), 3.36 (br s, 1H).

[0238] (2) Synthesis of 2-(1-bromo-4-methoxynaphthalen-2-yl)-2-(2-phenylhydroxy)ethan-1-ol Using the previously prepared 1-(1-bromo-4-methoxynaphthalen-2-yl)-2-hydroxyethan-1-one (37.46 mmol) as the starting material, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5.

[0239] (3) Synthesis of Intermediate 6 ((5-methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)methanol)

[0240] Using the previously prepared 2-(1-bromo-4-methoxynaphthalen-2-yl)-2-(2-phenylhydroxy)ethan-1-ol (25.98 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0241] Yield: 56%, light brown solid.

[0242] 1 H NMR (300 MHz, CDCl3) δ: 8.27 (d, J = 8.2 Hz, 1H), 7.44 - 7.39 (m, 7H), 7.22 (t, J = 7.5 Hz, 1H), 6.96 (s, 1H), 5.00 (s, 2H), 3.96 (s, 3H).

[0243] Preparation Example 7: Synthesis of Intermediate 7 (3-(Bromomethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole)

[0244] (1) Synthesis of 3-(Bromomethyl)-5-methoxy-1-phenyl-1H-benzo[g]indazole

[0245] Dissolve (5-Methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)methanol (14.5 mmol, Intermediate 6) in methylene chloride (100 mL). While stirring at room temperature, add PBr3 and react for 5 hours. After the reaction is complete, add water to terminate the reaction, and extract the reaction solution with methylene chloride. Wash the extract with brine, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, and purify by column chromatography.

[0246] Yield: 67%, brown solid.

[0247] 1 H NMR (300 MHz, CDCl3) δ: 8.40 (d, J = 8.8 Hz, 1H), 7.64 - 7.56 (m, 5H), 7.55 - 7.51 (m, 2H), 7.35 (t, J = 8.2 Hz, 1H), 7.05 (s, 1H), 4.95 (s, 2H), 4.12 (s, 3H).

[0248] (2) Synthesis of 3-(Bromomethyl)-1-phenyl-1H-benzo[g]indazol-5-ol

[0249] Dissolve 3-(Bromomethyl)-5-methoxy-1-phenyl-1H-benzo[g]indazole (5 mmol) in methylene chloride (30 mL). Then, lower the temperature to 0 °C, slowly add dropwise BBr3 (15 mmol), raise the temperature to room temperature, and react for 1 hour. After adding H2O to the reaction solution, extract with ethyl acetate. Recrystallize with methylene chloride and n-hexane to obtain a brown solid, which is used in the next step without further purification.

[0250] (3) Synthesis of Intermediate 7 (3-(Bromomethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole)

[0251] Dissolve 3-(Bromomethyl)-1-phenyl-1H-benzo[g]indazol-5-ol (7.60 mmol) in DMF (30 mL). Lower the temperature to 0 °C, add chloromethyl methyl ether (19.0 mmol) and N,N-diisopropylethylamine (19.0 mmol), slowly raise the temperature to room temperature and react. After the reaction is complete, add water to terminate the reaction, and extract the mixture with ethyl acetate. Wash the extract with brine, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, and purify by column chromatography.

[0252] Yield: 32%, white solid.

[0253] 1 H NMR (300 MHz, CDCl3) δ: 8.40 (d, J = 7.6 Hz, 1H), 7.62 - 7.54 (m, 7H), 7.38 - 7.35 (m, 2H), 5.48 (s, 2H), 5.05 (s, 2H), 3.61 (s, 3H).

[0254] Preparation Example 8: Synthesis of Intermediate 8 (5 - methoxy - 3 - methyl - 1H - benzo[g]indazole)

[0255] (1) Synthesis of (1 - (1 - bromo - 4 - methoxynaphthalen - 2 - yl)ethylidene)hydrazine

[0256] Using 1 - (1 - bromo - 4 - methoxynaphthalen - 2 - yl)ethan - 1 - one (11.0 mmol, Intermediate 4) and hydrazine monohydrate (12.1 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0257] (2) Synthesis of Intermediate 8 (5 - methoxy - 3 - methyl - 1H - benzo[g]indazole)

[0258] Using (1 - (1 - bromo - 4 - methoxynaphthalen - 2 - yl)ethylidene)hydrazine as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0259] Yield: 31%, light brown solid.

[0260] 1 H NMR (300 MHz, CDCl3) δ: 13.2 (s, 1H), 8.34 (d, J = 7.7 Hz, 1H), 8.20 (d, J = 7.7 Hz, 1H), 7.66 - 7.53 (m, 2H), 7.03 (s, 1H), 3.97 (s, 3H), 2.57 (s, 3H).

[0261] Preparation Example 9: Synthesis of Intermediate 9 (1 - (4 - fluorophenyl) - 5 - methoxy - 3 - methyl - 1H - benzo[g]indazole)

[0262] (1) Synthesis of 1 - (1 - (1 - bromo - 4 - methoxynaphthalen - 2 - yl)ethylidene) - 2 - (4 - fluorophenyl)hydrazine

[0263] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and 4-fluorophenylhydrazine (10.8 mmol) as starting materials and reactants, after synthesizing the title compound according to the procedure described in (1) of Preparation Example 5, it was used in the next reaction without further purification.

[0264] (2) Synthesis of Intermediate 9 (1-(4-fluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0265] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(4-fluorophenyl)hydrazine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0266] Yield: 32%, light brown solid.

[0267] 1 H NMR (300 MHz, DMSO-d6) δ: 8.41 - 8.38 (m, 1H), 7.57 - 7.52 (m, 4H), 7.36 - 7.33 (m, 1H), 7.28 - 7.25 (m, 2H), 6.92 - 6.90 (m, 1H), 4.10 (s, 3H), 2.66 (s, 3H).

[0268] Preparation Example 10: Synthesis of Intermediate 10 (1-(4-chlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0269] (1) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(4-chlorophenyl)hydrazine

[0270] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and 4-chlorophenylhydrazine as starting materials and reactants, after synthesizing the title compound according to the procedure described in (1) of Preparation Example 5, it was used in the next reaction without further purification.

[0271] (2) Synthesis of Intermediate 10 (1-(4-chlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0272] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(4-chlorophenyl)hydrazine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0273] Yield: 36%, light brown solid.

[0274] 1 1H NMR (300 MHz, DMSO-d6) δ: 8.37 - 8.31 (m, 1H), 7.61 - 7.58 (m, 1H), 7.55 - 7.50 (m, 5H), 7.37 - 7.30 (m, 1H), 6.89 (s, 1H), 4.08 (s, 3H), 2.64 (s, 3H).

[0275] Preparation Example 11: Synthesis of Intermediate 11 (1-(3,5-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0276] (1) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(3,5-difluorophenyl)hydrazine

[0277] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and 3,5-difluorophenylhydrazine (10.8 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0278] (2) Synthesis of Intermediate 11 (1-(3,5-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0279] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(3,5-difluorophenyl)hydrazine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0280] Yield: 41%, light brown solid.

[0281] 1 1H NMR (300 MHz, DMSO-d6) δ: 8.40 - 8.37 (m, 1H), 7.75 - 7.71 (m, 1H), 7.57 - 7.51 (m, 1H), 7.44 - 7.39 (m, 1H), 7.17 - 7.12 (m, 2H), 6.96 - 6.91 (m, 1H), 6.89 (s, 1H), 4.09 (s, 3H), 2.64 (s, 3H).

[0282] Preparation Example 12: Synthesis of Intermediate 12 (1-(2,4-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0283] (1) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(2,4-dichlorophenyl)hydrazine

[0284] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and 2,4-dichlorophenylhydrazine (10.8 mmol) as starting materials and reactants, after synthesizing the title compound according to the procedure described in (1) of Preparation Example 5, it was used for the next reaction without further purification.

[0285] (2) Synthesis of Intermediate 12 (1-(2,4-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0286] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(2,4-dichlorophenyl)hydrazine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0287] Yield: 53%, light brown solid.

[0288] 1 H NMR (300 MHz, DMSO-d6) δ: 8.37 - 8.34 (m, 1H), 7.65 (s, 1H), 7.55 - 7.46 (m, 3H), 7.35 - 7.30 (m, 1H), 7.24 - 7.19 (m, 1H), 6.91 (s, 1H), 4.08 (s, 3H), 2.66 (s, 3H).

[0289] Preparation Example 13: Synthesis of Intermediate 13 (5-methoxy-3-methyl-1-p-tolyl-1H-benzo[g]indazole)

[0290] (1) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-p-tolylhydrazine

[0291] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and p-tolylhydrazine (10.8 mmol) as starting materials and reactants, after synthesizing the title compound according to the procedure described in (1) of Preparation Example 5, it was used for the next reaction without further purification.

[0292] (2) Synthesis of Intermediate 13 (5-methoxy-3-methyl-1-p-tolyl-1H-benzo[g]indazole)

[0293] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-p-tolylhydrazine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0294] Yield: 26%, light brown solid.

[0295] 1 H NMR (300 MHz, DMSO-d6) δ: 8.36 - 8.30 (m, 1H), 7.61 - 7.56 (m, 1H), 7.53 - 7.43 (m, 3H), 7.36 - 7.33 (m, 3H), 6.90 (s, 1H), 4.08 (s, 3H), 2.64 (s, 3H), 2.49 (s, 3H).

[0296] Preparation Example 14: Synthesis of Intermediate 14 (5-methoxy-3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole)

[0297] (1) Synthesis of 2-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)hydrazinecarboximidoyl)pyridine

[0298] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and 2-hydrazinopyridine (10.8 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0299] (2) Synthesis of Intermediate 14 (5-methoxy-3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole)

[0300] Using 2-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)hydrazinecarboximidoyl)pyridine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0301] Yield: 30%, light brown solid.

[0302] 1 H NMR (300 MHz, DMSO-d6) δ: 8.65 - 8.62 (m, 1H), 8.39 - 8.36 (m, 1H), 8.05 - 7.89 (m, 2H), 7.83 - 7.71 (m, 1H), 7.61 - 7.49 (m, 1H), 7.47 - 7.33 (m, 2H), 6.90 - 6.87 (m, 1H), 4.08 (s, 3H), 2.65 (s, 3H).

[0303] Preparation Example 15: Synthesis of Intermediate 15 (5-methoxy-3-methyl-1-(pyridin-3-yl)-1H-benzo[g]indazole)

[0304] (1) Synthesis of 3-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)carbohydrazonoyl)pyridine

[0305] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and 3-hydrazinopyridine (10.8 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0306] (2) Synthesis of Intermediate 15 (5-methoxy-3-methyl-1-(pyridin-3-yl)-1H-benzo[g]indazole)

[0307] Using 3-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)carbohydrazonoyl)pyridine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0308] Yield: 22%, light brown solid.

[0309] 1 H NMR (300 MHz, DMSO-d6) δ: 8.93 - 8.85 (m, 1H), 8.80 - 8.71 (m, 1H), 8.44 - 8.36 (m, 1H), 7.97 - 7.89 (m, 1H), 7.61 - 7.48 (m, 3H), 7.41 - 7.32 (m, 1H), 6.92 - 6.87 (m, 1H), 4.09 (s, 3H), 2.67 (s, 3H).

[0310] Preparation Example 16: Synthesis of Intermediate 16 (1-(2,4-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0311] (1) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(2,4-difluorophenyl)hydrazine

[0312] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and 2,4-difluorophenylhydrazine (10.8 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0313] (2) Synthesis of Intermediate 16 (1-(2,4-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0314] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(2,4-difluorophenyl)hydrazine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0315] Yield: 37%, light brown solid.

[0316] 1 H NMR (300 MHz, DMSO-d6) δ: 8.42 - 8.39 (m, 1H), 7.69 (s, 1H), 7.56 - 7.47 (m, 3H), 7.39 - 7.33 (m, 1H), 7.30 - 7.26 (m, 1H), 6.96 (s, 1H), 4.09 (s, 3H), 2.68 (s, 3H).

[0317] Preparation Example 17: Synthesis of Intermediate 17 (5-methoxy-1-phenyl-1H-benzo[g]indazole)

[0318] (1) Synthesis of 1-bromo-4-methoxy-2-naphthaldehyde

[0319] 1-Bromo-N,4-dimethoxy-N-methyl-2-naphthamide (35.6 mmol, the product of step (1) of Preparation Example 4) was dissolved in 200 ml of THF, and the temperature of the reaction solution was cooled to 0 °C. Then, a solution of diisobutylaluminum hydride (71.3 mmol) was slowly added to the reaction solution, and the mixture was stirred for 10 minutes. After the temperature of the reaction solution was raised to room temperature, the mixture was stirred for 10 hours. After the reaction was terminated, the reaction solution was cooled to 0 °C, and then 100 ml of 1 M aqueous NH4Cl solution was slowly added. After stirring for 10 minutes, the organic layer was separated. The aqueous layer was extracted with ethyl acetate, the organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, and then purified by column chromatography.

[0320] Yield: 42%, white solid.

[0321] 1 H NMR (300 MHz, CDCl3) δ: 10.66 (s, 1H), 8.50 - 8.47 (m, 1H), 8.33 - 8.31 (m, 1H), 7.71 - 7.68 (m, 2H), 7.30 (s, 1H), 4.07 (s, 3H).

[0322] (2) Synthesis of 1-((1-bromo-4-methoxynaphthalen-2-yl)methylene)-2-phenylhydrazine

[0323] Using 1-bromo-4-methoxy-2-naphthaldehyde (7.5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0324] (3) Synthesis of Intermediate 17 (5-methoxy-1-phenyl-1H-benzo[g]indazole)

[0325] Using 1-((1-bromo-4-methoxynaphthalen-2-yl)methylene)-2-phenylhydrazine (5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0326] Yield: 27%, brown solid.

[0327] 1 H NMR (300 MHz, CDCl3) δ: 8.34 - 8.36 (m, 1H), 8.14 (s, 1H), 7.58 - 7.49 (m, 7H), 7.35 - 7.30 (m, 1H), 7.00 (s, 1H), 4.06 (s, 3H).

[0328] Preparation Example 18: Synthesis of Intermediate 18 (5-methoxy-1-phenyl-3-(trifluoromethyl)-1H-benzo[g]indazole)

[0329] (1) Synthesis of 1-(1-bromo-4-methoxynaphthalen-2-yl)-2,2,2-trifluoroethanol

[0330] 1-Bromo-4-methoxy-2-naphthaldehyde (6.04 mmol) was dissolved in THF (7.5 mL). The temperature was lowered to 0 °C, TMS-CF3 (15.08 mmol) and a TBAF solution (1 M THF solution, 0.6 mmol) were added, and the mixture was reacted for 8 hours. 1 mL of H2O was added and the mixture was stirred for 10 hours. Then, more water was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography.

[0331] Yield: 90%, opaque yellow liquid.

[0332] 1 H NMR (300 MHz, CDCl3) δ: 8.32 - 8.27 (m, 2H), 7.64 - 7.55 (m, 2H), 7.10 (s, 1H), 6.00 - 5.98 (m, 1H), 4.04 (s, 3H).

[0333] (2) Synthesis of 1-(1-bromo-4-methoxynaphthalen-2-yl)-2,2,2-trifluoroethanone

[0334] Suspend 1-(1-bromo-4-methoxynaphthalen-2-yl)-2,2,2-trifluoroethanol (6 mmol) and IBX (18 mmol) in ethyl acetate (100 mL). Raise the temperature and react under reflux conditions for 3 hours. After the reaction is complete, filter the reaction solution, concentrate the filtrate under reduced pressure, and purify by column chromatography.

[0335] Yield: 89%, yellow solid.

[0336] 1 H NMR (300 MHz, CDCl3) δ: 8.37 - 8.31 (m, 2H), 7.74 - 7.63 (m, 2H), 6.80 (s, 1H), 4.04 (s, 3H).

[0337] (3) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)-2,2,2-trifluoroethylidene)-2-phenylhydrazine

[0338] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)-2,2,2-trifluoroethanone (5.88 mmol) as the starting material, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0339] (4) Synthesis of Intermediate 18 (5-methoxy-1-phenyl-3-(trifluoromethyl)-1H-benzo[g]indazole)

[0340] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)-2,2,2-trifluoroethylidene)-2-phenylhydrazine (4.13 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0341] Yield: 44%, light yellow solid.

[0342] 1 H NMR (300 MHz, CDCl3) δ: 8.47 - 8.39 (m, 1H), 8.31 - 8.28 (m, 1H), 7.72 - 7.48 (m, 5H), 7.39 - 7.34 (m, 1H), 7.21 - 7.03 (m, 1H), 4.02 (s, 3H).

[0343] Preparation Example 19: Synthesis of Intermediate 19 (7-fluoro-5-methoxy-3-methyl-1-phenyl-1H-benzo[g]indazole)

[0344] (1) Synthesis of methyl 6-fluoro-4-hydroxy-2-naphthoate

[0345] 4-Fluorobenzaldehyde (16.3 mmol) was used as a starting material, and the title compound was synthesized according to the procedure described in (1) of Preparation Example 3.

[0346] Yield: 26% overall, white solid.

[0347] 1 H NMR (300 MHz, CDCl3) δ: 8.18 (s, 1H), 7.91 - 7.79 (m, 1H), 7.42 (s, 1H), 7.33 - 7.27 (m, 1H), 5.68 (br s, 1H), 3.94 (s, 3H).

[0348] (2) Synthesis of methyl 6-fluoro-4-methoxy-2-naphthoate

[0349] Using methyl 6-fluoro-1-hydroxy-3-naphthoate as a starting material, the title compound as a light brown solid was obtained according to the procedure described in (2) of Preparation Example 3 and was used in the next reaction without further purification.

[0350] (3) Synthesis of methyl 1-bromo-6-fluoro-4-methoxy-2-naphthoate

[0351] Using methyl 6-fluoro-4-methoxy-2-naphthoate as a starting material, the title compound was synthesized according to the procedure described in (3) of Preparation Example 3.

[0352] Yield: 92%, light orange solid.

[0353] 1 H NMR (300 MHz, CDCl3) δ: 8.46 - 8.41 (m, 1H), 7.92 - 7.87 (m, 1H), 7.44 - 7.39 (m, 1H), 7.06 (s, 1H), 4.03 (s, 3H), 4.01 (s, 3H).

[0354] (4) Synthesis of 1-bromo-6-fluoro-4-methoxy-2-naphthoic acid

[0355] Using methyl 1-bromo-6-fluoro-4-methoxy-2-naphthoate as a starting material, the title compound was synthesized according to the procedure described in (4) of Preparation Example 3.

[0356] Yield: 96%, white solid.

[0357] 11H NMR (300 MHz, CDCl3) δ: 8.54 - 8.49 (m, 1H), 7.94 - 7.91 (m, 1H), 7.47 - 7.41 (m, 1H), 7.25 (s, 1H), 4.06 (s, 3H).

[0358] (5) Synthesis of 1 - bromo - 6 - fluoro - N,4 - dimethoxy - N - methyl - 2 - naphthamide

[0359] Using 1 - bromo - 6 - fluoro - 4 - methoxy - 2 - naphthoic acid (3.34 mmol) as the starting material, the title compound was synthesized according to the procedure described in (1) of Preparation Example 4 and used in the next reaction without further purification.

[0360] Yield: 90%, yellow liquid.

[0361] (6) Synthesis of 1 - (1 - bromo - 6 - fluoro - 4 - methoxynaphthalen - 2 - yl)ethanone

[0362] Using 1 - bromo - 6 - fluoro - N,4 - dimethoxy - N - methyl - 2 - naphthamide (13.3 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 2.

[0363] Yield: 46%, white solid.

[0364] 1 1H NMR (300 MHz, CDCl3) δ: 8.35 - 8.30 (m, 1H), 7.90 - 7.87 (m, 1H), 7.44 - 7.39 (m, 1H), 6.75 (s, 1H), 4.01 (s, 3H), 2.73 (s, 3H).

[0365] (7) Synthesis of 1 - (1 - (1 - bromo - 6 - fluoro - 4 - methoxynaphthalen - 2 - yl)ethylidene) - 2 - phenylhydrazine

[0366] Using 1 - (1 - bromo - 6 - fluoro - 4 - methoxynaphthalen - 2 - yl)ethanone (6.15 mmol) as the starting material, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0367] (8) Synthesis of Intermediate 19 (7 - fluoro - 5 - methoxy - 3 - methyl - 1 - phenyl - 1H - benzo[g]indazole)

[0368] Using 1 - (1 - (1 - bromo - 6 - fluoro - 4 - methoxynaphthalen - 2 - yl)ethylidene) - 2 - phenylhydrazine (1.81 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0369] Yield: 25%, brown solid.

[0370] 1 H NMR (300 MHz, CDCl3) δ: 8.08 - 7.90 (m, 1H), 7.62 - 7.48 (m, 6H), 7.17 - 7.03 (m, 1H), 6.85 (s, 1H), 4.07 (s, 3H), 2.64 (s, 3H).

[0371] Preparation Example 20: Synthesis of Intermediate 20 (1-(3,5-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0372] (1) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(3,5-dichlorophenyl)hydrazine

[0373] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (3.6 mmol, Intermediate 4) and 3,5-dichlorophenylhydrazine hydrochloride (3.96 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0374] (2) Synthesis of Intermediate 20 (1-(3,5-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0375] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(3,5-dichlorophenyl)hydrazine (3.2 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0376] Yield: 24%, brown solid.

[0377] 1 H NMR (300 MHz, DMSO-d6) δ: 8.34 (d, 1H), 7.63 (d, 1H), 7.50 (t, 1H), 7.45 (d, 2H), 7.41 (t, 1H), 7.37 (t, 1H), 6.81 (s, 1H), 3.97 (s, 3H), 2.56 (s, 3H).

[0378] Preparation Example 21: Synthesis of Intermediate 21 (methyl 4-(5-methoxy-3-methyl-1H-benzo[g]indazol-1-yl)benzoate)

[0379] (1) Synthesis of methyl 4-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)hydrazino)benzoate

[0380] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (7.2 mmol, Intermediate 4) and methyl 4-hydrazinylbenzoate hydrochloride (7.92 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0381] (2) Synthesis of Intermediate 21 (methyl 4-(5-methoxy-3-methyl-1H-benzo[g]indazol-1-yl)benzoate)

[0382] Using methyl 4-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)hydrazinyl)benzoate (3.99 mmol) as a starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5 and used in the next reaction without further purification.

[0383] Yield: 22%, light brown solid.

[0384] Preparation Example 22: Synthesis of Intermediate 22 (5-methoxy-3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole)

[0385] (1) Synthesis of 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(naphthalen-1-yl)hydrazine

[0386] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (2.1 mmol, Intermediate 4) and 1-naphthylhydrazine hydrochloride (2.31 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0387] (2) Synthesis of Intermediate 22 (5-methoxy-3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole)

[0388] Using 1-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)-2-(naphthalen-1-yl)hydrazine (1.82 mmol) as a starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5 and used in the next reaction without further purification.

[0389] Yield: 51%, light brown solid.

[0390] Preparation Example 23: Synthesis of Intermediate 23 (1-(5-chloropyridin-3-yl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0391] (1) Synthesis of 3-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)hydrazino)-5-chloropyridine

[0392] Using 1-(1-bromo-4-methoxynaphthalen-2-yl)ethan-1-one (10.75 mmol, Intermediate 4) and 5-chloro-3-hydrazinopyridine hydrochloride (11.83 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5 and used in the next reaction without further purification.

[0393] (2) Synthesis of Intermediate 23 (1-(5-chloropyridin-3-yl)-5-methoxy-3-methyl-1H-benzo[g]indazole)

[0394] Using 3-(2-(1-(1-bromo-4-methoxynaphthalen-2-yl)ethylidene)hydrazino)-5-chloropyridine (8.12 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0395] Yield: 40%, brown solid.

[0396] 1 H NMR (300 MHz, DMSO-d6) δ: 8.60 - 8.58 (m, 1H), 8.39 - 8.36 (m, 1H), 8.05 - 7.90 (m, 1H), 7.80 - 7.71 (m, 1H), 7.60 - 7.53 (m, 1H), 7.40 - 7.31 (m, 2H), 6.88 (s, 1H), 4.08 (s, 3H), 2.65 (s, 3H).

[0397] Example 1: Synthesis of Compound 1 (1-phenylimidazo[1,2-a]quinoline-4,5-dione)

[0398] (1) Synthesis of 5-(benzyloxy)-1-phenylimidazo[1,2-a]quinoline

[0399] 4-(Benzyloxy)quinolin-2-amine (2 mmol) and sulfur (S8, 4 mmol) were dissolved in cyclohexane (2 mL) and DMSO (4 mL). Then, 2-phenylacetaldehyde (4 mmol) was added, the temperature was raised to 120 °C, and the reaction was carried out for 30 minutes. After the reaction was complete, H2O was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was collected, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography.

[0400] Yield: 31%, yellow solid.

[0401] 11H NMR (300 MHz, DMSO-d6) δ: 8.27 - 8.24 (m, 1H), 7.55 - 7.27 (m, 12H), 6.95 (s, 1H), 5.28 (s, 2H).

[0402] (2) Synthesis of 1-phenylimidazo[1,2-a]quinolin-5-ol

[0403] Dissolve 5-(benzyloxy)-1-phenylimidazo[1,2-a]quinoline (0.8 mmol) in methylene chloride (2 mL). Lower the temperature to 0 °C, slowly add dropwise BBr3 (1.68 mmol), and after slowly rising to room temperature, react for 1 hour. After adding H2O to the reaction solution, extract with ethyl acetate. Recrystallize with methylene chloride and n-hexane again and purify.

[0404] Yield: 66%, brown solid.

[0405] 1 1H NMR (300 MHz, DMSO-d6) δ: 8.14 - 8.12 (d, J = 7.0 Hz, 1H), 7.51 - 7.34 (m, 8H), 7.26 (s, 1H), 6.75 (br s, 1H).

[0406] (3) Synthesis of Compound 1 (1-phenylimidazo[1,2-a]quinoline-4,5-dione) Add 1-phenylimidazo[1,2-a]quinolin-5-ol (0.38 mmol) and dissolve it in DMF (10 mL). Then, add IBX (0.38 mmol) all at once and react for 2 hours. After the reaction is completed, add saturated sodium bicarbonate solution to terminate the reaction. Extract the reaction solution with ethyl acetate, collect the organic layer and dry it with anhydrous magnesium sulfate, and after concentration under reduced pressure, purify by column chromatography.

[0407] Yield: 65%, yellow solid.

[0408] 1 1H NMR (300 MHz, DMSO-d6) δ: 8.20 - 8.17 (m, 1H), 7.60 - 7.50 (m, 5H), 7.46 (s, 1H), 7.44 - 7.33 (m, 2H), 7.11 - 7.08 (m, 1H).

[0409] Example 2: Synthesis of Compound 2 (1-(4-fluorophenyl)imidazo[1,2-a]quinoline-4,5-dione)

[0410] (1) Synthesis of 5-(benzyloxy)-1-(4-fluorophenyl)imidazo[1,2-a]quinoline

[0411] 4-(Benzyloxy)quinolin-2-amine (0.3 mmol, Intermediate 1), sulfur (S8, 0.6 mmol) were added and dissolved in cyclohexane (0.3 mL) and DMSO (0.6 mL). Then, 2-(4-fluorophenyl)acetaldehyde (0.6 mmol) was added, the temperature was raised to 120 °C and reacted for 30 minutes. After the reaction was complete, H2O was added, extracted with ethyl acetate, the organic layer was collected and dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography.

[0412] Yield: 35%, light yellow solid.

[0413] 1 H NMR (300 MHz, CDCl3) δ: 8.28 - 8.26 (m, 1H), 7.64 - 7.20 (m, 13H), 6.94 (s, 1H), 5.28 (s, 2H).

[0414] (2) Synthesis of 1-(4-fluorophenyl)imidazo[1,2-a]quinolin-5-ol

[0415] 5-(Benzyloxy)-1-(4-fluorophenyl)imidazo[1,2-a]quinoline (0.14 mmol) was dissolved in methylene chloride (3 mL), and the temperature was lowered to 0 °C. BBr3 (1.68 mmol) was slowly added dropwise, the temperature was slowly raised to room temperature, and reacted for 1 hour. After adding H2O to terminate the reaction, the reaction solution was extracted with ethyl acetate. Recrystallized with methylene chloride and n-hexane again to obtain a brown solid, which was used in the next reaction without further purification.

[0416] (3) Synthesis of Compound 2 (1-(4-fluorophenyl)imidazo[1,2-a]quinoline-4,5-dione) 1-(4-fluorophenyl)imidazo[1,2-a]quinolin-5-ol (0.38 mmol) was dissolved in DMF (10 mL), IBX (0.38 mmol) was added at once and reacted for 2 hours. After the reaction was completed, saturated sodium bicarbonate solution was added to terminate the reaction. The reaction solution was extracted with ethyl acetate, the organic layer was collected and dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography.

[0417] Yield: 49%, orange solid.

[0418] 1 H NMR (300 MHz, DMSO-d6) δ: 8.02 - 7.99 (m, 1H), 7.60 - 7.55 (m, 2H), 7.50 - 7.37 (m, 5H), 6.94 - 6.92 (m, 1H).

[0419] Example 3: Synthesis of Compound 3 (1-isopropylimidazo[1,2-a]quinoline-4,5-dione)

[0420] (1) Synthesis of 5-(benzyloxy)-1-isopropylimidazo[1,2-a]quinoline

[0421] Using 4-(benzyloxy)quinolin-2-amine (0.3 mmol, Intermediate 1) and 3-methylbutanal (0.6 mmol) as starting materials and reactants, the title compound was synthesized according to the procedure described in (1) of Example 1.

[0422] Yield: 41%, yellow solid.

[0423] 1 H NMR (300 MHz, CDCl3) δ: 8.31 - 8.22 (m, 2H), 7.65 - 7.60 (m, 1H), 7.52 - 7.28 (m, 7H) 6.90 (s, 1H), 5.28 (s, 2H), 3.78 - 3.69 (m, 1H), 1.48 (d, J = 6.6 Hz, 6H).

[0424] (2) Synthesis of 1-isopropylimidazo[1,2-a]quinolin-5-ol

[0425] Using 5-(benzyloxy)-1-isopropylimidazo[1,2-a]quinoline (0.8 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification.

[0426] (3) Synthesis of Compound 3 (1-isopropylimidazo[1,2-a]quinoline-4,5-dione)

[0427] Using 1-isopropylimidazo[1,2-a]quinolin-5-ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0428] Yield: 17%, orange solid.

[0429] 1 H NMR (300 MHz, CDCl3) δ: 8.23 - 8.21 (m, 1H), 7.84 - 7.76 (m, 2H), 7.48 - 7.39 (m, 2H), 3.63 - 3.56 (m, 1H), 1.51 (d, J = 6.6 Hz, 1H).

[0430] Example 4: Synthesis of Compound 4 (1-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoline-4,5-dione)

[0431] (1) Synthesis of 5-(Benzyloxy)-1-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoline

[0432] Using 4-(benzyloxy)quinolin-2-amine (0.3 mmol, Intermediate 1) and 2-(4-(trifluoromethyl)phenyl)acetaldehyde (0.6 mmol), the title compound was synthesized according to the procedure described in (1) of Example 1.

[0433] Yield: 20%, light yellow solid.

[0434] 1 H NMR (300 MHz, CDCl3) δ: 8.30 (dd, J = 7.9, 1.3 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.4 Hz, 2H), 7.55 - 7.36 (m, 9H), 6.95 (s, 1H), 5.30 (s, 2H).

[0435] (2) Synthesis of 1-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]quinolin-5-ol

[0436] Using 5-(benzyloxy)-1-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoline (0.8 mmol) as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification of the obtained light brown solid.

[0437] (3) Synthesis of Compound 4 (1-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]quinoline-4,5-dione

[0438] Using 1-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]quinolin-5-ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0439] Yield: 43%, orange solid.

[0440] 1 H NMR (300 MHz, CDCl3) δ: 8.23 - 8.20 (m, 1H), 7.84 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 8.2 Hz, 2H), 7.50 - 7.37 (m, 3H), 7.05 - 7.02 (m, 1H).

[0441] Example 5: Synthesis of Compound 5 (Ethyl 4,5-dioxo-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxylate

[0442] (1) Synthesis of Ethyl 5-Hydroxyimidazo[1,2-a]quinoline-2-carboxylate

[0443] Using ethyl 5-(benzyloxy)imidazo[1,2-a]quinoline-2-carboxylate (0.5 mmol, Intermediate 2) as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification of the obtained solid.

[0444] (2) Synthesis of Compound 5 (Ethyl 4,5-Dioxo-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxylate)

[0445] Using ethyl 5-hydroxyimidazo[1,2-a]quinoline-2-carboxylate (0.5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0446] Yield: 57%, yellow solid.

[0447] 1 H NMR (300 MHz, CDCl3) δ: 8.37 (s, 1H), 8.29 - 8.26 (m, 1H), 7.88 - 7.86 (m, 1H), 7.66 - 7.55 (m, 2H), 4.46 (q, J = 7.1 Hz, 2H), 1.44 (t, J = 7.1 Hz, 3H).

[0448] Example 6: Synthesis of Compound 6 (Ethyl 4,5-Dioxo-1-phenyl-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxylate)

[0449] (1) Synthesis of Ethyl 5-(Benzyloxy)-1-bromoimidazo[1,2-a]quinoline-2-carboxylate

[0450] Ethyl 5-(benzyloxy)imidazo[1,2-a]quinoline-2-carboxylate (1 mmol, Intermediate 2) was dissolved in acetonitrile (10 mL). After stirring for 5 minutes, N-bromosuccinimide (1.1 mmol) was added and the reaction was carried out at room temperature for 12 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure and purified by column chromatography.

[0451] Yield: 59%, dark brown solid.

[0452] 11H NMR (300 MHz, DMSO-d6) δ: 9.50 (d, J = 8.6 Hz, 1H), 8.32 (d, J = 8.2 Hz, 1H), 7.71 - 7.68 (m, 1H), 7.58 - 7.34 (m, 6H), 6.60 (s, 1H), 5.26 (s, 2H), 4.48 (q, J = 7.2 Hz, 2H), 1.47 (t, J = 7.2 Hz, 3H).

[0453] (2) Synthesis of ethyl 5-(benzyloxy)-1-phenylimidazo[1,2-a]quinoline-2-carboxylate

[0454] Ethyl 5-(benzyloxy)-1-bromoimidazo[1,2-a]quinoline-2-carboxylate (1 mmol), Pd(PPh3)4 (5 mol%), K2CO3 (2.5 mmol), and phenylboronic acid (2 mmol) were dissolved in 1,4-dioxane (9.5 mL) and H2O (0.5 mL), and the reaction was carried out at 100 °C. After the reaction was complete, 50 mL of water was added to the reaction solution, and then it was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and then purified by column chromatography.

[0455] Yield: 92%, yellow solid.

[0456] 1 1H NMR (300 MHz, CDCl3) δ: 8.27 - 8.25 (m, 1H), 7.58 - 7.39 (m, 10H), 7.25 - 7.16 (m, 2H), 6.95 (s, 1H), 5.29 (s, 2H), 4.27 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1 Hz, 3H).

[0457] (3) Synthesis of ethyl 5-hydroxy-1-phenylimidazo[1,2-a]quinoline-2-carboxylate

[0458] Using ethyl 5-(benzyloxy)-1-phenylimidazo[1,2-a]quinoline-2-carboxylate as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification of the obtained light brown solid.

[0459] (4) Synthesis of compound 6 (ethyl 4,5-dioxo-1-phenyl-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxylate)

[0460] Using ethyl 5-hydroxy-1-phenylimidazo[1,2-a]quinoline-2-carboxylate (0.5 mmol) as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0461] Yield: 54%, dark yellow solid.

[0462] 1 H NMR (300 MHz, CDCl3) δ: 8.23 - 8.21 (m, 1H), 7.65 - 7.57 (m, 3H), 7.51 - 7.48 (m, 2H), 7.40 - 7.33 (m, 2H), 6.81 - 6.78 (m, 1H), 4.28 (q, J = 7.1 Hz, 2H) 1.25 (t, J = 7.1 Hz, 3H).

[0463] Example 7: Synthesis of Compound 7 (N,N - dimethyl - 4,5 - dioxo - 1 - phenyl - 4,5 - dihydroimidazo[1,2 - a]quinoline - 2 - carboxamide)

[0464] (1) Synthesis of 4,5 - dioxo - 1 - phenyl - 4,5 - dihydroimidazo[1,2 - a]quinoline - 2 - carboxylic acid Ethyl 4,5 - dioxo - 1 - phenyl - 4,5 - dihydroimidazo[1,2 - a]quinoline - 2 - carboxylate (2 mmol, Compound 5) and lithium hydroxide (4 mmol) were dissolved in 1,4 - dioxane (10 mL) and H2O (10 mL), and then reacted at 0 °C for 12 hours. After the reaction was complete, 3M aqueous hydrochloric acid was added to the reaction solution, and the pH value was adjusted to 1. 100 mL of water was added and the mixture was filtered to obtain a white solid, which was dried and used in the next step without further purification.

[0465] (2) Synthesis of Compound 7 (N,N - dimethyl - 4,5 - dioxo - 1 - phenyl - 4,5 - dihydroimidazo[1,2 - a]quinoline - 2 - carboxamide)

[0466] 4,5 - Dioxo - 1 - phenyl - 4,5 - dihydroimidazo[1,2 - a]quinoline - 2 - carboxylic acid (1 mmol), HATU (1.1 mmol), diisopropylethylamine (1.2 mmol) and dimethylamine (1.3 mmol) were dissolved in dimethylformamide (10 mL). After reacting at room temperature for 12 hours, water was added to the reaction solution to terminate the reaction, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product was purified by column chromatography.

[0467] Yield: 90%, dark yellow solid.

[0468] 1 H NMR (300 MHz, CDCl3) δ: 7.69 - 7.52 (m, 7H), 7.39 - 7.34 (m, 1H), 7.24 - 7.22 (m, 1H), 6.81 - 6.79 (m, 1H), 3.21 (s, 3H), 3.03 (s, 3H).

[0469] Example 8: Synthesis of Compound 8 (N-Methyl-4,5-dioxo-1-phenyl-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxamide)

[0470] Using 4,5-dioxo-1-phenyl-4,5-dihydroimidazo[1,2-a]quinoline-2-carboxylic acid (1 mmol) prepared in (1) of Example 7 and methylamine ethanol solution (1.3 mmol), the title compound was synthesized according to the procedure described in (2) of Example 6.

[0471] Yield: 50%, dark yellow solid.

[0472] 1 H NMR (300 MHz, CDCl3) δ: 7.69 - 7.65 (m, 3H), 7.56 - 7.50 (m, 3H), 7.38 - 7.33 (m, 1H), 7.27 - 7.22 (m, 1H), 6.76 - 6.73 (m, 1H) 2.92 (s, 3H).

[0473] Example 9: Synthesis of Compound 9 (3-Methyl-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0474] (1) Synthesis of 3-Methyl-1-phenyl-1H-benzo[g]indazol-5-ol

[0475] Using Intermediate 5 as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1.

[0476] Yield: 80%, light brown solid.

[0477] 1 H NMR (300 MHz, CDCl3) δ: 8.33 - 8.31 (m, 1H), 7.63 - 7.51 (m, 7H), 7.37 - 7.32 (m, 1H), 6.96 (s, 3H), 5.33 (br s, 1H), 2.61 (s, 3H).

[0478] (2) Synthesis of Compound 9 (3-Methyl-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0479] Using 3-Methyl-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0480] Yield: 70%, yellow solid.

[0481] 11H NMR (300 MHz, CDCl3) δ: 8.19 - 8.16 (m, 1H), 7.64 - 7.62 (m, 3H), 7.56 - 7.51 (m, 2H), 7.46 - 7.31 (m, 2H), 6.89 - 6.86 (m, 1H), 2.63 (s, 3H).

[0482] Example 10: Synthesis of Compound 10 (3 - Isopropyl - 1 - phenyl - 1H - benzo[g]indazole - 4,5 - dione)

[0483] (1) Synthesis of 5 - Methoxy - 1 - phenyl - 1H - benzo[g]indazole - 3 - carbaldehyde

[0484] Dissolve (5 - Methoxy - 1 - phenyl - 1H - benzo[g]indazol - 3 - yl)methanol (26.17 mmol, Intermediate 6) in methylene chloride (100 mL). Add PCC (26.17 mmol) and diatomaceous earth (5.64 g) to the reaction solution and react for 30 minutes. After completion of the reaction, add water to the reaction mixture and extract with methylene chloride. Wash the extract with brine, dry over anhydrous magnesium sulfate, and concentrate under reduced pressure, followed by purification by column chromatography.

[0485] Yield: 66%, light brown solid.

[0486] 1 1H NMR (300 MHz, CDCl3) δ: 10.22 (s, 1H), 8.28 (d, J = 8.2 Hz, 1H), 7.49 - 7.46 (m, 5H), 7.44 - 7.36 (m, 2H), 7.25 (t, J = 7.8 Hz, 1H), 6.96 (s, 1H), 4.02 (s, 3H).

[0487] (2) Synthesis of 1 - (5 - Methoxy - 1 - phenyl - 1H - benzo[g]indazol - 3 - yl)ethan - 1 - ol

[0488] Dissolve 5 - Methoxy - 1 - phenyl - 1H - benzo[g]indazole - 3 - carbaldehyde (9.59 mmol) in THF. Lower the temperature below 0 °C and slowly add methylmagnesium bromide solution (24 mmol, 3 M THF solution) and react for 5 hours. After completion of the reaction, add saturated aqueous ammonium chloride solution to the reaction mixture to terminate the reaction, and extract with ethyl acetate. Wash the extract with brine, dry over anhydrous magnesium sulfate, and concentrate under reduced pressure, followed by purification by column chromatography.

[0489] Yield: 92%, light yellow solid.

[0490] 11H NMR (300 MHz, CDCl3) δ: 8.36 (d, J = 8.2 Hz, 1H), 7.53 - 7.48 (m, 7H), 7.31 - 7.28 (m, 1H), 7.12 (m, 1H), 5.41 - 5.39 (m, 1H), 4.05 (s, 3H), 1.78 (d, J = 6.4 Hz, 3H).

[0491] (3) Synthesis of 1-(5-methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)ethan-1-one

[0492] Using the previously prepared 1-(5-methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)ethan-1-ol as the starting material, the title compound was synthesized according to the procedure described in (1) of Example 10.

[0493] Yield: 80%, light yellow solid.

[0494] 1 1H NMR (300 MHz, CDCl3) δ: 8.40 (d, J = 2.8 Hz, 1H), 7.73 (s, 1H), 7.63 - 7.57 (m, 5H), 7.56 - 7.51 (m, 1H), 7.48 - 7.44 (m, 1H), 7.36 - 7.34 (m, 1H), 4.05 (s, 3H), 2.77 (s, 3H).

[0495] (4) Synthesis of 5-methoxy-1-phenyl-3-(prop-1-en-2-yl)-1H-benzo[g]indazole

[0496] Methyltriphenylphosphonium bromide (35.3 mmol) was dissolved in THF (50 mL). After the temperature was lowered to -78 °C, a solution of n-butyllithium (35.3 mmol, 2.5 M hexane solution) was added dropwise and the reaction was carried out for 2 hours. At the same temperature, a solution of 1-(5-methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)ethan-1-one (7.06 mmol) in THF (20 mL) was added dropwise. After the temperature was slowly raised to room temperature, the reaction was carried out. After the reaction was completed, the reaction solution was quenched by adding saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography.

[0497] Yield: 95%, yellow solid.

[0498] 11H NMR (300 MHz, CDCl3) δ: 8.38 (d, J = 2.9 Hz, 1H), 7.57 - 7.50 (m, 6H), 7.35 - 7.30 (m, 1H), 7.22 (s, 1H), 5.76 (s, 1H), 5.47 (s, 1H), 4.09 (s, 3H), 2.39 (s, 3H).

[0499] (5) Synthesis of 3 - isopropyl - 5 - methoxy - 1 - phenyl - 1H - benzo[g]indazole

[0500] Dissolve 5 - methoxy - 1 - phenyl - 3 - (prop - 1 - en - 2 - yl) - 1H - benzo[g]indazole (6.71 mmol) and Pd / C (5 mol%) in methanol (50 mL). Fill the reaction vessel with hydrogen and stir overnight at room temperature. After the reaction is complete, filter through diatomaceous earth, concentrate the filtrate under reduced pressure, and purify by column chromatography.

[0501] Yield: 40%, white solid.

[0502] 1 1H NMR (300 MHz, CDCl3) δ: 8.37 (d, J = 2.8 Hz, 1H), 7.62 - 7.48 (m, 7H), 7.35 - 7.30 (m, 1H), 6.86 (s, 1H), 4.09 (s, 3H) 3.54 - 3.43 (m, 1H), 1.56 - 1.53 (d, J = 6.5 Hz, 6H).

[0503] (6) Synthesis of 3 - isopropyl - 1 - phenyl - 1H - benzo[g]indazol - 5 - ol

[0504] Using 3 - isopropyl - 5 - methoxy - 1 - phenyl - 1H - benzo[g]indazole as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1.

[0505] Yield: 95%, light brown solid.

[0506] 1 1H NMR (300 MHz, CDCl3) δ: 8.21 (d, J = 8.2 Hz, 1H), 7.60 - 7.49 (m, 7H), 7.33 - 7.29 (m, 1H), 6.97 (s, 1H), 6.67 (s, 1H), 3.39 - 3.32 (m, 1H), 1.46 - 1.44 (d, J = 6.5 Hz, 6H).

[0507] (7) Synthesis of Compound 10 (3 - isopropyl - 1 - phenyl - 1H - benzo[g]indazole - 4,5 - dione)

[0508] The title compound was synthesized using 3-isopropyl-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material and following the procedure described in (3) of Example 1.

[0509] Yield: 96%, yellow solid.

[0510] 1 H NMR (300 MHz, CDCl3) δ: 8.15 (d, J = 7.7 Hz, 1H), 7.62 - 7.61 (m, 3H), 7.55 - 7.53 (m, 2H), 7.40 (t, J = 7.6 Hz, 1H), 7.32 (m, 1H), 6.82 (d, J = 2.6 Hz, 1H), 3.57 (m, 1H), 1.39 (d, J = 2.2 Hz, 6H).

[0511] Example 11: Synthesis of Compound 11 (3-heptyl-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0512] (1) Synthesis of 3-(hept-1-en-1-yl)-5-methoxy-1-phenyl-1H-benzo[g]indazole

[0513] The title compound was synthesized using n-hexyltriphenylphosphonium bromide (35.3 mmol) and 1-(5-methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)ethan-1-one (7.06 mmol) prepared in (1) of Example 10 and following the procedure described in (4) of Example 9.

[0514] Yield: 95%, yellow solid.

[0515] 1 H NMR (300 MHz, CDCl3) δ: 8.39 (d, J = 8.2 Hz, 1H), 7.66 - 7.50 (m, 7H), 7.35 (t, J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.69 (d, J = 11.2 Hz, 1H), 6.00 (m, 1H), 4.09 (s, 3H), 2.67 (m, 2H), 1.53 (m, 2H), 1.48 - 1.28 (m, 4H), 0.88 (t, J = 5.5 Hz, 3H).

[0516] (2) Synthesis of 3-heptyl-5-methoxy-1-phenyl-1H-benzo[g]indazole

[0517] The title compound was synthesized using 3-(hept-1-en-1-yl)-5-methoxy-1-phenyl-1H-benzo[g]indazole (9.11 mmol) as the starting material and following the procedure described in (5) of Example 10.

[0518] Yield: 96%, white solid.

[0519] 1 H NMR (300 MHz, CDCl3) δ: 8.37 (d, J = 8.2 Hz, 1H), 7.62 - 7.49 (m, 7H), 7.33 (t, J = 7.6 Hz, 1H), 6.94 (s, 1H), 4.09 (s, 3H), 3.03 (t, J = 7.6 Hz, 2H), 1.88 (m, 2H), 1.48 - 1.27 (m, 8H), 0.87 (t, J = 5.5 Hz, 3H).

[0520] (3) Synthesis of 3 - heptyl - 1 - phenyl - 1H - benzo[g]indazol - 5 - ol

[0521] Using 3 - heptyl - 5 - methoxy - 1 - phenyl - 1H - benzo[g]indazole as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0522] (4) Synthesis of Compound 11 (3 - heptyl - 1 - phenyl - 1H - benzo[g]indazole - 4,5 - dione)

[0523] Using 3 - heptyl - 1 - phenyl - 1H - benzo[g]indazol - 5 - ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0524] Yield: 86%, yellow solid.

[0525] 1 H NMR (300 MHz, CDCl3) δ: 8.16 (d, J = 7.6 Hz, 1H), 7.64 - 7.62 (m, 3H), 7.55 - 7.53 (m, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 2.99 (t, J = 7.6 Hz, 2H), 1.77 (m, 2H), 1.43 - 1.11 (m, 8H), 0.86 (t, J = 5.9 Hz, 3H).

[0526] Example 12: Synthesis of Compound 12 (3 - phenethyl - 1 - phenyl - 1H - benzo[g]indazole - 4,5 - dione)

[0527] (1) Synthesis of 5 - methoxy - 1 - phenyl - 3 - styryl - 1H - benzo[g]indazole

[0528] Using phenyltriphenylphosphonium bromide (47.9 mmol) and 1-(5-methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)ethan-1-one (9.6 mmol) prepared in (1) of Example 10, the title compound was synthesized according to the procedure described in (4) of Example 9.

[0529] Yield: 96%, yellow solid.

[0530] 1 H NMR (300 MHz, CDCl3) δ: 8.39 (d, J = 7.7 Hz, 1H), 7.62 - 7.51 (m, 10H), 7.42 - 7.34 (m, 3H), 7.32 - 7.24 (m, 2H), 7.20 (s, 1H), 4.14 (s, 3H).

[0531] (2) Synthesis of 5-methoxy-3-phenethyl-1-phenyl-1H-benzo[g]indazole

[0532] Using 5-methoxy-1-phenyl-3-styryl-1H-benzo[g]indazole (9.21 mmol) as the starting material, the title compound was synthesized according to the procedure described in (5) of Example 10.

[0533] Yield: 98%, white solid.

[0534] 1 H NMR (300 MHz, CDCl3) δ: 8.35 (d, J = 8.2 Hz, 1H), 7.60 - 7.58 (m, 6H), 7.51 (t, J = 7.6 Hz, 1H), 7.35 - 7.30 (m, 1H), 7.31 - 7.29 (m, 5H), 6.71 (s, 1H), 4.00 (s, 3H), 3.36 (t, J = 7.4 Hz, 2H), 3.20 (t, J = 7.4 Hz, 2H).

[0535] (3) Synthesis of 3-phenethyl-1-phenyl-1H-benzo[g]indazol-5-ol

[0536] Using 5-methoxy-3-phenethyl-1-phenyl-1H-benzo[g]indazole as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0537] (4) Synthesis of Compound 12 (3-phenethyl-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0538] The title compound was synthesized using 3-isopropyl-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material and according to the steps described in (3) of Example 1.

[0539] Yield: 66%, yellow solid.

[0540] 1 H NMR (300 MHz, CDCl3) δ: 8.17 (d, J = 7.6 Hz, 1H), 7.64 - 7.62 (m, 3H), 7.53 - 7.52 (m, 2H), 7.45 (t, J = 7.6 Hz, 1H), 7.37 - 7.29 (m, 5H), 7.24 (t, J = 7.6 Hz, 1H), 6.87 (d, J = 7.6 Hz, 1H), 3.30 (t, J = 7.0 Hz, 2H), 3.11 (t, J = 7.0 Hz, 2H).

[0541] Example 13: Synthesis of Compound 13 (1,3-diphenyl-1H-benzo[g]indazole-4,5-dione)

[0542] (1) Synthesis of (1-bromo-4-methoxynaphthalen-2-yl)(phenyl)methanone

[0543] The title compound was synthesized using 1-bromo-N,4-dimethoxy-N-methyl-2-naphthamide prepared in (1) of Preparation Example 4 and phenylmagnesium bromide according to the steps described in (2) of Preparation Example 4.

[0544] Yield: 80%, white solid.

[0545] 1 H NMR (300 MHz, DMSO-d6) δ: 8.35 - 8.29 (m, 2H), 7.79 - 7.67 (m, 5H), 7.57 - 7.54 (m, 2H), 7.05 (s, 1H), 3.97 (s, 3H).

[0546] (2) Synthesis of 1-((1-bromo-4-methoxynaphthalen-2-yl)(phenyl)methylene)-2-phenylhydrazine

[0547] The title compound was synthesized using (1-bromo-4-methoxynaphthalen-2-yl)(phenyl)methanone as the starting material and according to the steps described in (1) of Preparation Example 5.

[0548] (3) Synthesis of 5-methoxy-1,3-diphenyl-1H-benzo[g]indazole

[0549] The title compound was synthesized using 1-((1-bromo-4-methoxynaphthalen-2-yl)(phenyl)methylene)-2-phenylhydrazine as a starting material and according to the procedure described in (2) of Preparation Example 5.

[0550] Yield: 50%, light brown solid.

[0551] 1 H NMR (300 MHz, DMSO-d6) δ: 8.29 (d, J = 2.8 Hz, 1H), 7.91 - 7.88 (m, 2H), 7.55 - 7.36 (m, 9H), 7.34 - 7.28 (m, 1H), 7.25 - 7.19 (m, 1H), 6.89 (s, 1H), 3.98 (s, 3H).

[0552] (4) Synthesis of 1,3-diphenyl-1H-benzo[g]indazol-5-ol

[0553] The title compound was synthesized using 5-methoxy-1,3-diphenyl-1H-benzo[g]indazole as a starting material and according to the procedure described in (2) of Example 1.

[0554] Yield: 90%, light brown solid.

[0555] 1 H NMR (300 MHz, DMSO-d6) δ: 8.20 (d, J = 2.9 Hz, 1H), 7.89 - 7.85 (m, 2H), 7.52 - 7.38 (m, 9H), 7.30 - 7.28 (m, 1H), 7.23 - 7.16 (m, 1H), 6.85 (br s, 1H).

[0556] (5) Synthesis of Compound 13 (1,3-diphenyl-1H-benzo[g]indazole-4,5-dione)

[0557] The title compound was synthesized using 1,3-diphenyl-1H-benzo[g]indazol-5-ol as a starting material and according to the procedure described in (3) of Example 1.

[0558] Yield: 94%, yellow solid.

[0559] 1 H NMR (300 MHz, DMSO-d6) δ: 8.21 - 8.15 (m, 3H), 7.68 - 7.61 (m, 5H), 7.48 - 7.44 (m, 4H), 7.39 - 7.34 (m, 1H), 6.82 (d, J = 1.8 Hz, 1H).

[0560] Example 14: Synthesis of Compound 14 (3-(4-Fluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0561] (1) Synthesis of (1-Bromo-4-methoxynaphthalen-2-yl)(4-fluorophenyl)methanone

[0562] Using 1-bromo-N,4-dimethoxy-N-methyl-2-naphthamide synthesized in (1) of Preparation Example 4 and 4-fluorophenylmagnesium bromide, the title compound was synthesized according to the procedure described in (2) of Preparation Example 4.

[0563] Yield: 80%, white solid.

[0564] 1 H NMR (300 MHz, DMSO-d6) δ: 8.34 - 8.29 (m, 2H), 7.79 - 7.65 (m, 5H), 7.56 - 7.54 (m, 1H), 7.03 (s, 1H), 3.97 (s, 3H).

[0565] (2) Synthesis of 1-((1-Bromo-4-methoxynaphthalen-2-yl)(4-fluorophenyl)methylene)-2-phenylhydrazine

[0566] Using (1-bromo-4-methoxynaphthalen-2-yl)(4-fluorophenyl)methanone as the starting material, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5.

[0567] (3) Synthesis of 3-(4-Fluorophenyl)-5-methoxy-1-phenyl-1H-benzo[g]indazole

[0568] Using 1-((1-bromo-4-methoxynaphthalen-2-yl)(4-fluorophenyl)methylene)-2-phenylhydrazine as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0569] Yield: 45%, light gray solid.

[0570] 1 H NMR (300 MHz, DMSO-d6) δ: 8.27 (d, J = 2.8 Hz, 1H), 7.87 - 7.84 (m, 2H), 7.56 - 7.39 (m, 8H), 7.33 - 7.28 (m, 1H), 7.23 - 7.21 (m, 1H), 6.72 (s, 1H), 3.98 (s, 3H).

[0571] (4) Synthesis of 3-(4-Fluorophenyl)-1-phenyl-1H-benzo[g]indazol-5-ol

[0572] Using 3-(4-fluorophenyl)-5-methoxy-1-phenyl-1H-benzo[g]indazole as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1.

[0573] Yield: 89%, light brown solid.

[0574] 1 H NMR (300 MHz, DMSO-d6) δ: 8.23 (d, J = 2.8 Hz, 1H), 7.86 - 7.82 (m, 2H), 7.54 - 7.34 (m, 8H), 7.31 - 7.28 (m, 1H), 7.20 - 7.18 (m, 1H), 6.70 (br s, 1H).

[0575] (5) Synthesis of Compound 14 (3-(4-fluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0576] Using 3-(4-fluorophenyl)-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0577] Yield: 90%, yellow solid.

[0578] 1 H NMR (300 MHz, DMSO-d6) δ: 8.19 - 8.17 (m, 3H,), 7.78 - 7.60 (m, 5H), 7.48 - 7.43 (m, 1H), 7.37 - 7.33 (m, 1H), 7.16 - 7.11 (m, 2H), 6.87 (d, J = 7.7 Hz, 1H).

[0579] Example 15: Synthesis of Compound 15 (3-(3,4-difluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0580] (1) Synthesis of (1-bromo-4-methoxynaphthalen-2-yl)(3,4-difluorophenyl)methanone

[0581] Using 1-bromo-N,4-dimethoxy-N-methyl-2-naphthamide synthesized in (1) of Preparation Example 4 and 3,4-difluorophenylmagnesium bromide, the title compound was synthesized according to the procedure described in (2) of Preparation Example 4.

[0582] Yield: 75%, white solid.

[0583] 11H NMR (300 MHz, DMSO-d6) δ: 8.30 - 8.26 (m, 2H), 7.76 - 7.62 (m, 4H), 7.53 - 7.50 (m, 1H), 7.01 (s, 1H), 3.96 (s, 3H).

[0584] (2) Synthesis of 1-((1-bromo-4-methoxynaphthalen-2-yl)(3,4-difluorophenyl)methylene)-2-phenylhydrazine

[0585] Using (1-bromo-4-methoxynaphthalen-2-yl)(3,4-difluorophenyl)methanone as the starting material, the title compound was synthesized according to the procedure described in (1) of Preparation Example 5.

[0586] (3) Synthesis of 3-(3,4-difluorophenyl)-5-methoxy-1-phenyl-1H-benzo[g]indazole

[0587] Using 1-((1-bromo-4-methoxynaphthalen-2-yl)(3,4-difluorophenyl)methylene)-2-phenylhydrazine as the starting material, the title compound was synthesized according to the procedure described in (2) of Preparation Example 5.

[0588] Yield: 40%, light gray solid.

[0589] 1 1H NMR (300 MHz, DMSO-d6) δ: 8.22 (d, J = 2.8 Hz, 1H), 7.84 - 7.81 (m, 2H), 7.52 - 7.34 (m, 7H), 7.30 - 7.28 (m, 1H), 7.20 - 7.17 (m, 1H), 6.68 (s, 1H), 3.96 (s, 3H).

[0590] (4) Synthesis of 3-(3,4-difluorophenyl)-1-phenyl-1H-benzo[g]indazol-5-ol

[0591] Using 3-(3,4-difluorophenyl)-5-methoxy-1-phenyl-1H-benzo[g]indazole as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 1.

[0592] Yield: 92%, light brown solid.

[0593] 1 1H NMR (300 MHz, DMSO-d6) δ: 8.20 (d, J = 2.8 Hz, 1H), 7.84 - 7.80 (m, 2H), 7.50 - 7.30 (m, 7H), 7.29 - 7.28 (m, 1H), 7.19 - 7.16 (m, 1H), 6.63 (br s, 1H).

[0594] (5) Synthesis of Compound 15 (3-(3,4-difluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0595] Using 3-(3,4-difluorophenyl)-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0596] Yield: 94%, yellow solid.

[0597] 1 H NMR (300 MHz, DMSO-d6) δ: 8.19 - 8.04 (m, 3H), 7.68 - 7.66 (m, 3H), 7.66 - 7.60 (m, 2H), 7.47 - 7.44 (m, 1H), 7.39 - 7.33 (m, 1H), 7.25 - 7.22 (m, 1H), 6.88 - 6.86 (m, 1H).

[0598] Example 16: Synthesis of Compound 16 (3-(bromomethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0599] Using 3-(bromomethyl)-1-phenyl-1H-benzo[g]indazol-5-ol prepared in (2) of Preparation Example 7 as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0600] Yield: 46%, yellow solid.

[0601] 1 H NMR (300 MHz, CDCl3) δ: 8.20 (d, J = 7.6 Hz, 1H), 7.66 - 7.62 (m, 3H), 7.58 - 7.55 (m, 2H), 7.48 (t, J = 7.2 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 6.89 (d, J = 8.2 Hz, 1H), 4.80 (s, 2H).

[0602] Example 17: Synthesis of Compound 17 (3-((dimethylamino)methyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0603] Dissolve 3-(bromomethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione (3.50 mmol, Compound 16) in THF (30 mL). After lowering the temperature to 0 °C, add dimethylamine (35.0 mmol), raise the temperature to room temperature and stir. After completion of the reaction, add water to the reaction solution to terminate the reaction. Extract the reaction solution with ethyl acetate, wash the extract with brine, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, and purify by column chromatography.

[0604] Yield: 58%, yellow solid.

[0605] 1 H NMR (300 MHz, CDCl3) δ: 8.16 (d, J = 7.6 Hz, 1H), 7.63 - 7.61 (m, 3H), 7.55 - 7.52 (m, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 3.91 (s, 2H), 2.44 (s, 6H).

[0606] Example 18: Synthesis of Compound 18 (3-(methoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0607] (1) Synthesis of 5-(methoxymethoxy)-3-(methoxymethyl)-1-phenyl-1H-benzo[g]indazole

[0608] Add NaH (3.65 mmol) to a mixed solvent of methanol (4.86 mmol) and DMF (20 mL), lower the temperature to 0 °C and stir. After stirring for 30 minutes, add 3-(bromomethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole (2.43 mmol, Intermediate 7), and raise the temperature to room temperature for reaction. After completion of the reaction, add water to the reaction solution to terminate the reaction, and extract with ethyl acetate. Wash the extract with brine, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, and purify by column chromatography.

[0609] Yield: 95%, light yellow solid.

[0610] 1 H NMR (300 MHz, CDCl3) δ: 8.40 (d, J = 8.2 Hz, 1H), 7.62 - 7.56 (m, 6H), 7.55 - 7.52 (m, 1H), 7.41 - 7.37 (m, 1H), 7.35 (t, J = 8.4 Hz, 1H), 5.48 (s, 2H), 4.91 (s, 2H), 3.61 (s, 3H), 3.50 (s, 3H).

[0611] (2) Synthesis of 3-(methoxymethyl)-1-phenyl-1H-benzo[g]indazol-5-ol Dissolve 5-(methoxymethoxy)-3-(methoxymethyl)-1-phenyl-1H-benzo[g]indazole (2.31 mmol) in methanol (20 mL). While stirring at room temperature, add 2 drops of concentrated hydrochloric acid, raise the temperature, and react under reflux conditions. After the reaction is completed, concentrate the reaction solution under reduced pressure, add water, and extract with ethyl acetate. Dry the organic layer with anhydrous magnesium sulfate and concentrate under reduced pressure, and use it for the next reaction without further purification.

[0612] (3) Synthesis of Compound 18 (3-(methoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0613] Using 3-(methoxymethyl)-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0614] Yield: 75%, yellow solid.

[0615] 1 H NMR (300 MHz, CDCl3) δ: 8.16 (d, J = 7.6 Hz, 1H), 7.63 - 7.61 (m, 3H), 7.55 - 7.52 (m, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 6.87 (d, J = 7.6 Hz, 1H), 4.86 (s, 2H), 3.57 (s, 3H).

[0616] Example 19: Synthesis of Compound 19 (3-(isopropoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0617] (1) Synthesis of 3-(isopropoxymethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole

[0618] Using isopropanol (0.37 mL) and 3-(bromomethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole (2.43 mmol, Intermediate 7), the title compound was synthesized according to the procedure described in (1) of Example 18.

[0619] Yield: 39%, light yellow solid.

[0620] 11H NMR (300 MHz, CDCl3) δ: 8.40 (d, J = 8.2 Hz, 1H), 7.62 - 7.58 (m, 6H), 7.54 - 7.49 (m, 2H), 7.32 (t, J = 7.4 Hz, 1H), 5.46 (s, 2H), 4.97 (s, 2H), 3.87 - 3.84 (m, 1H), 3.60 (s, 3H), 1.29 (d, J = 5.9 Hz, 6H).

[0621] (2) Synthesis of 3-(isopropoxymethyl)-1-phenyl-1H-benzo[g]indazol-5-ol

[0622] Using 3-(isopropoxymethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole as the starting material, the title compound was synthesized according to the procedure described in (2) of Example 18 and used in the next reaction without further purification.

[0623] (3) Synthesis of Compound 19 (3-(isopropoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0624] Using 3-(isopropoxymethyl)-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was synthesized according to the procedure described in (3) of Example 1.

[0625] Yield: 53%, yellow solid.

[0626] 1 1H NMR (300 MHz, CDCl3) δ: 8.16 (d, J = 7.6 Hz, 1H), 7.62 - 7.60 (m, 3H), 7.54 - 7.53 (m, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 7.6 Hz, 1H), 4.84 (s, 2H), 3.90 (m, 1H), 1.27 (d, J = 6.4 Hz, 6H).

[0627] Example 20: Synthesis of Compound 20 (1-isopropyl-3-methyl-1H-benzo[g]indazole-4,5-dione) and Compound 21 (2-isopropyl-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0628] (1) Synthesis of a mixture of 1-isopropyl-5-methoxy-3-methyl-1H-benzo[g]indazole and 2-isopropyl-5-methoxy-3-methyl-2H-benzo[g]indazole

[0629] 5-Methoxy-3-methyl-1H-benzo[g]indazole (2.1 mmol, Intermediate 8) was dissolved in DMF. After the temperature was lowered to 0 °C, NaH (3.18 mmol) was added, and after the temperature was raised to room temperature, the mixture was stirred. Subsequently, 2-bromopropane (4.24 mmol) was added and the reaction was carried out for 8 hours. The reaction was terminated by adding H2O, and the reaction solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a mixture of 1-isopropyl-5-methoxy-3-methyl-1H-benzo[g]indazole and 2-isopropyl-5-methoxy-3-methyl-2H-benzo[g]indazole, which was used in the next reaction without further purification.

[0630] (2) Synthesis of a mixture of 1-isopropyl-3-methyl-1H-benzo[g]indazol-5-ol and 2-isopropyl-3-methyl-2H-benzo[g]indazol-5-ol

[0631] Using the mixture of 1-isopropyl-5-methoxy-3-methyl-1H-benzo[g]indazole and 2-isopropyl-5-methoxy-3-methyl-2H-benzo[g]indazole as the starting material, the mixture of the title compounds was obtained according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification.

[0632] (3) Synthesis of Compound 20 (1-isopropyl-3-methyl-1H-benzo[g]indazole-4,5-dione) and Compound 21 (2-isopropyl-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0633] Using the mixture of 1-isopropyl-3-methyl-1H-benzo[g]indazol-5-ol and 2-isopropyl-3-methyl-2H-benzo[g]indazol-5-ol as the starting material, the mixture of the title compounds was obtained according to the procedure described in (3) of Example 1, and Compound 20 and Compound 21 were separated from this mixture.

[0634] (Compound 20) Yield: 7%, yellow solid.

[0635] 1 H NMR (300 MHz, CDCl3) δ: 8.04 - 8.01 (m, 2H), 7.82 - 7.77 (m, 1H), 7.61 - 7.56 (m, 1H), 5.22 - 5.14 (m, 1H), 2.39 (s, 3H), 1.51 (d, J = 5.9 Hz, 6H).

[0636] (Compound 21) Yield: 6%, yellow solid.

[0637] 11H NMR (300 MHz, CDCl3) δ: 8.11 - 8.03 (m, 2H), 7.66 - 7.62 (m, 1H), 7.45 - 7.40 (m, 1H), 4.54 - 4.50 (m, 1H), 2.65 (s, 3H), 1.56 (d, J = 6.5 Hz, 6H).

[0638] Example 21: Synthesis of Compound 22 (1,3 - dimethyl - 1H - benzo[g]indazole - 4,5 - dione) and Compound 23 (2,3 - dimethyl - 2H - benzo[g]indazole - 4,5 - dione)

[0639] (1) Synthesis of a mixture of 5 - methoxy - 1,3 - dimethyl - 1H - benzo[g]indazole and 5 - methoxy - 2,3 - dimethyl - 2H - benzo[g]indazole

[0640] Using 5 - methoxy - 3 - methyl - 1H - benzo[g]indazole (2.1 mmol, Intermediate 8) and methyl iodide (4.24 mmol), a mixture of the title compounds was obtained according to the procedure described in (1) of Example 20 and used in the next reaction without further purification of the mixture.

[0641] (2) Synthesis of a mixture of 1,3 - dimethyl - 1H - benzo[g]indazole - 5 - ol and 2,3 - dimethyl - 2H - benzo[g]indazole - 5 - ol

[0642] Using the mixture of 5 - methoxy - 1,3 - dimethyl - 1H - benzo[g]indazole and 5 - methoxy - 2,3 - dimethyl - 2H - benzo[g]indazole as the starting material, a mixture of the title compounds was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification of the mixture.

[0643] (3) Synthesis of Compound 22 (1,3 - dimethyl - 1H - benzo[g]indazole - 4,5 - dione) and Compound 23 (2,3 - dimethyl - 2H - benzo[g]indazole - 4,5 - dione)

[0644] Using the mixture of 1,3 - dimethyl - 1H - benzo[g]indazole - 5 - ol and 2,3 - dimethyl - 2H - benzo[g]indazole - 5 - ol as the starting material, a mixture of the title compounds was obtained according to the procedure described in (3) of Example 1, and Compound 22 and Compound 23 were separated from the mixture.

[0645] (Compound 22) Yield: 2%, yellow solid.

[0646] 11H NMR (300 MHz, CDCl3) δ: 8.25 - 8.20 (m, 1H), 7.83 - 7.79 (m, 1H), 7.76 - 7.72 (m, 1H), 7.56 - 7.52 (m, 1H), 4.26 (s, 3H), 2.55 (s, 3H).

[0647] (Compound 23) Yield: 1.5%, yellow solid.

[0648] 1 1H NMR (300 MHz, CDCl3) δ: 8.14 - 8.10 (m, 1H), 7.98 - 7.93 (m, 1H), 7.68 - 7.64 (m, 1H), 7.49 - 7.46 (m, 1H), 3.89 (s, 3H), 2.66 (s, 3H).

[0649] Example 22: Synthesis of Compound 24 (3 - ((1H - imidazol - 1 - yl)methyl)-1 - phenyl - 1H - benzo[g]indazole - 4,5 - dione)

[0650] (1) Synthesis of 3 - ((1H - imidazol - 1 - yl)methyl)-5 - methoxy - 1 - phenyl - 1H - benzo[g]indazole

[0651] Dissolve 3 - (bromomethyl)-5 - methoxy - 1 - phenyl - 1H - benzo[g]indazole (0.33 mmol) synthesized in (1) of Preparation Example 7 and imidazole (0.66 mmol) in DMF. After cooling the temperature to 0 °C, add NaH (3.18 mmol) to the reaction solution, raise the temperature to room temperature, and react for 12 hours. Add H2O to terminate the reaction, and extract the reaction solution with ethyl acetate. Dry the organic layer with anhydrous magnesium sulfate, concentrate under reduced pressure, and purify by column chromatography.

[0652] 1 1H NMR (300 MHz, CDCl3) δ: 8.34 (m, 1H), 7.75 (s, 1H), 7.60 - 7.50 (m, 7H), 7.34 (m, 1H), 7.10 (m, 2H), 6.45 (m, 1H), 5.55 (s, 2H), 3.95 (s, 3H).

[0653] (2) Synthesis of 3 - ((1H - imidazol - 1 - yl)methyl)-1 - phenyl - 1H - benzo[g]indazole - 5 - ol

[0654] Use 3 - ((1H - imidazol - 1 - yl)methyl)-5 - methoxy - 1 - phenyl - 1H - benzo[g]indazole as the starting material, and obtain the title compound according to the procedure described in (2) of Example 1. It is used in the next reaction without further purification.

[0655] (3) Synthesis of Compound 24 (3-((1H-imidazol-1-yl)methyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0656] Using 3-((1H-imidazol-1-yl)methyl)-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0657] Yield: 60%, yellow solid.

[0658] 1 H NMR (300 MHz, CDCl3) δ: 8.15 (m, 1H), 7.78 (s, 1H), 7.66 - 7.64 (m, 3H), 7.52 - 7.50 (m, 2H), 7.44 (m, 1H), 7.34 (m, 1H), 7.22 (m, 1H), 7.02 (m, 1H), 6.84 (m, 1H), 5.44 (s, 2H).

[0659] Example 23: Synthesis of Compound 25 (1-(4-fluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0660] (1) Synthesis of 1-(4-fluorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol

[0661] Using 1-(4-fluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification.

[0662] (2) Synthesis of Compound 25 (1-(4-fluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0663] Using 1-(4-fluorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0664] Yield: 40%, yellow solid.

[0665] 1 H NMR (300 MHz, CDCl3) δ: 8.03 - 7.98 (m, 1H), 7.72 - 7.68 (m, 2H), 7.55 - 7.50 (m, 4H), 6.78 - 6.75 (m, 1H), 2.45 (s, 3H).

[0666] Example 24: Synthesis of Compound 26 (1-(4-chlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0667] (1) Synthesis of 1-(4-chlorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol

[0668] Using 1-(4-chlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0669] (2) Synthesis of Compound 26 (1-(4-chlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0670] Using 1-(4-chlorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0671] Yield: 44%, yellow solid.

[0672] 1 H NMR (300 MHz, CDCl3) δ: 8.12 - 8.10 (m, 1H), 7.58 - 7.53 (m, 2H), 7.48 - 7.45 (m, 2H), 7.44 - 7.36 (m, 2H), 6.90 (s, 1H), 2.56 (s, 3H).

[0673] Example 25: Synthesis of Compound 27 (1-(3,5-difluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0674] (1) Synthesis of 1-(3,5-difluorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol

[0675] Using 1-(3,5-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0676] (2) Synthesis of Compound 27 (1-(3,5-difluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0677] Using 1-(3,5-difluorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0678] Yield: 12%, yellow solid.

[0679] 1 H NMR (300 MHz, CDCl3) δ: 8.17 - 8.15 (m, 1H), 7.51 - 7.44 (m, 2H), 7.13 - 7.08 (m, 3H), 6.99 - 6.97 (m, 1H), 2.59 (s, 3H).

[0680] Example 26: Synthesis of Compound 28 (1-(2,4-dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0681] (1) Synthesis of 1-(2,4-dichlorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol

[0682] Using 1-(2,4-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification.

[0683] (2) Synthesis of Compound 28 (1-(2,4-dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0684] Using 1-(2,4-dichlorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0685] Yield: 32%, yellow solid.

[0686] 1 H NMR (300 MHz, CDCl3) δ: 8.17 - 8.15 (m, 1H), 7.69 (s, 1H), 7.60 - 7.54 (m, 2H), 7.50 - 7.40 (m, 2H), 6.72 - 6.70 (m, 1H), 2.61 (s, 3H).

[0687] Example 27: Synthesis of Compound 29 (3-methyl-1-p-tolyl-1H-benzo[g]indazole-4,5-dione)

[0688] (1) Synthesis of 3-methyl-1-p-tolyl-1H-benzo[g]indazol-5-ol

[0689] Using 5-methoxy-3-methyl-1-p-tolyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0690] (2) Synthesis of Compound 29 (3-methyl-1-p-tolyl-1H-benzo[g]indazole-4,5-dione)

[0691] Using 3-methyl-1-p-tolyl-1H-benzo[g]indazole-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0692] Yield: 27%, yellow solid.

[0693] 1 H NMR (300 MHz, CDCl3) δ: 8.12 - 8.10 (m, 1H), 7.40 - 7.32 (m, 6H), 6.90 - 6.88 (m, 1H), 2.58 (s, 3H), 2.51 (s, 3H).

[0694] Example 28: Synthesis of Compound 30 (3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole-4,5-dione)

[0695] (1) Synthesis of 3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole-5-ol

[0696] Using 5-methoxy-3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0697] (2) Synthesis of Compound 30 (3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole-4,5-dione)

[0698] Using 3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0699] Yield: 21%, yellow solid.

[0700] 11H NMR (300 MHz, CDCl3) δ: 8.69 - 8.66 (m, 1H), 8.20 - 8.14 (m, 1H), 8.09 - 8.06 (m, 1H), 7.78 - 7.74 (m, 1H), 7.59 - 7.56 (m, 1H), 7.46 - 7.42 (m, 2H), 7.08 - 6.94 (m, 1H), 2.66 - 2.63 (s, 3H).

[0701] Example 29: Synthesis of Compound 31 (3 - Methyl - 1 - (pyridin - 3 - yl) - 1H - benzo[g]indazole - 4,5 - dione)

[0702] (1) Synthesis of 3 - Methyl - 1 - (pyridin - 3 - yl) - 1H - benzo[g]indazol - 5 - ol

[0703] Using 5 - Methoxy - 3 - methyl - 1 - (pyridin - 3 - yl) - 1H - benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification.

[0704] (2) Synthesis of Compound 31 (3 - Methyl - 1 - (pyridin - 3 - yl) - 1H - benzo[g]indazole - 4,5 - dione)

[0705] Using 3 - Methyl - 1 - (pyridin - 3 - yl) - 1H - benzo[g]indazol - 5 - ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0706] Yield: 27%, yellow solid.

[0707] 1 1H NMR (300 MHz, CDCl3) δ: 8.90 - 8.86 (m, 2H), 8.25 - 8.21 (m, 1H), 7.97 - 7.94 (m, 1H), 7.66 - 7.62 (m, 1H), 7.52 - 7.49 (m, 1H), 7.43 - 7.40 (m, 1H), 6.90 - 6.88 (m, 1H), 2.65 (s, 3H).

[0708] Example 30: Synthesis of Compound 32 (1 - (2,4 - Difluorophenyl) - 3 - methyl - 1H - benzo[g]indazole - 4,5 - dione)

[0709] (1) Synthesis of 1 - (2,4 - Difluorophenyl) - 3 - methyl - 1H - benzo[g]indazol - 5 - ol

[0710] Using 1-(2,4-difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0711] (2) Synthesis of Compound 32 (1-(2,4-difluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0712] Using 1-(2,4-difluorophenyl)-3-methyl-1H-benzo[g]indazole-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0713] Yield: 27%, yellow solid.

[0714] 1 H NMR (300 MHz, CDCl3) δ: 8.14 - 8.12 (m, 1H), 7.67 - 7.60 (m, 1H), 7.48 - 7.41 (m, 2H), 7.19 - 7.12 (m, 2H), 6.85 - 6.83 (m, 1H), 2.58 (s, 3H).

[0715] Example 31: Synthesis of Compound 33 (1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0716] (1) Synthesis of 1-phenyl-1H-benzo[g]indazole-5-ol

[0717] Using 5-methoxy-1-phenyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0718] (2) Synthesis of Compound 33 (1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0719] Using 1-phenyl-1H-benzo[g]indazole-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0720] Yield: 30%, yellow solid.

[0721] 11H NMR (300 MHz, CDCl3) δ: 8.23 (s, 1H), 8.20 - 8.17 (m, 1H), 7.64 - 7.63 (m, 3H), 7.54 - 7.50 (m, 2H), 7.47 - 7.42 (m, 1H), 7.37 - 7.32 (m, 1H), 6.90 - 6.87 (m, 1H).

[0722] Example 32: Synthesis of Compound 34 (1 - Phenyl - 3 - (trifluoromethyl)-1H - benzo[g]indazole - 4,5 - dione)

[0723] (1) Synthesis of 1 - Phenyl - 3 - (trifluoromethyl)-1H - benzo[g]indazol - 5 - ol

[0724] Using 5 - Methoxy - 1 - phenyl - 3 - (trifluoromethyl)-1H - benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0725] (2) Synthesis of Compound 34 (1 - Phenyl - 3 - (trifluoromethyl)-1H - benzo[g]indazole - 4,5 - dione)

[0726] Using 1 - Phenyl - 3 - (trifluoromethyl)-1H - benzo[g]indazol - 5 - ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0727] Yield: 19%, yellow solid.

[0728] 1 1H NMR (300 MHz, CDCl3) δ: 8.23 - 8.20 (m, 1H), 7.68 - 7.66 (m, 3H), 7.56 - 7.48 (m, 3H), 7.41 - 7.36 (m, 1H), 6.89 - 6.87 (m, 1H).

[0729] Example 33: Synthesis of Compound 35 (7 - Fluoro - 3 - methyl - 1 - phenyl - 1H - benzo[g]indazole - 4,5 - dione)

[0730] (1) Synthesis of 7 - Fluoro - 3 - methyl - 1 - phenyl - 1H - benzo[g]indazol - 5 - ol

[0731] Using 7 - Fluoro - 5 - methoxy - 3 - methyl - 1 - phenyl - 1H - benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0732] (2) Synthesis of Compound 35 (7-Fluoro-3-methyl-1-phenyl-1H-benzo[g]indazole-4,5-dione)

[0733] Using 7-fluoro-3-methyl-1-phenyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0734] Yield: 29%, yellow solid.

[0735] 1 H NMR (300 MHz, CDCl3) δ: 7.85 - 7.82 (m, 1H), 7.63 - 7.59 (m, 3H), 7.58 - 7.46 (m, 2H), 7.26 - 7.25 (m, 1H), 7.09 - 7.04 (m, 1H), 6.88 - 6.82 (m, 1H), 2.61 (s, 3H).

[0736] Example 34: Synthesis of Compound 36 (1-(3,5-Dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0737] (1) Synthesis of 1-(4-Chlorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol

[0738] Using 1-(3,5-dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole (Intermediate 20) as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0739] (2) Synthesis of Compound 36 (1-(3,5-Dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0740] Using 1-(3,5-dichlorophenyl)-3-methyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0741] Yield: 59%, yellow solid.

[0742] 1 H NMR (300 MHz, CDCl3) δ: 8.16 (d, 1H), 7.62 (s, 1H), 7.49 (m, 4H), 6.98 (d, 1H), 2.62 (s, 3H).

[0743] Example 35: Synthesis of Compound 37 (4-(3-Methyl-4,5-dioxo-4,5-dihydro-1H-benzo[g]indazol-1-yl)benzoic acid)

[0744] (1) Synthesis of 4-(5-Hydroxy-3-methyl-1H-benzo[g]indazol-1-yl)benzoic acid

[0745] Using methyl 4-(5-methoxy-3-methyl-1H-benzo[g]indazol-1-yl)benzoate as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0746] (2) Synthesis of Compound 37 (4-(3-Methyl-4,5-dioxo-4,5-dihydro-1H-benzo[g]indazol-1-yl)benzoic acid)

[0747] Using 4-(5-hydroxy-3-methyl-1H-benzo[g]indazol-1-yl)benzoic acid as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0748] Yield: 48%, yellow solid.

[0749] 1 H NMR (300 MHz, CDCl3) δ: 13.40 (s, 1H), 8.19 - 8.17 (m, 2H), 7.97 - 7.95 (m, 1H), 7.73 - 7.72 (m, 2H), 7.49 - 7.48 (m, 2H), 6.80 (s, 1H), 2.43 (s, 3H).

[0750] Example 36: Synthesis of Compound 38 (3-Methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole-4,5-dione)

[0751] (1) Synthesis of 3-Methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazol-5-ol

[0752] Using 5-methoxy-3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification.

[0753] (2) Synthesis of Compound 38 (3-Methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole-4,5-dione)

[0754] Using 3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0755] Yield: 43%, yellow solid.

[0756] 1 H NMR (300 MHz, CDCl3) δ: 8.14 - 8.13 (m, 2H), 8.03 - 8.01 (m, 1H), 7.68 - 7.66 (m, 2H), 7.60 - 7.59 (m, 1H), 7.52 - 7.50 (m, 1H), 7.41 - 7.31 (m, 2H), 7.12 - 7.10 (m, 1H), 6.44 (s, 1H), 2.70 (s, 3H).

[0757] Example 37: Synthesis of Compound 39 (1-(5-chloropyridin-3-yl)-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0758] (1) Synthesis of 1-(5-chloropyridin-3-yl)-3-methyl-1H-benzo[g]indazol-5-ol

[0759] Using 1-(5-chloropyridin-3-yl)-5-methoxy-3-methyl-1H-benzo[g]indazole as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification.

[0760] (2) Synthesis of Compound 39 (3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole-4,5-dione)

[0761] Using 3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0762] Yield: 38%, yellow solid.

[0763] 1 H NMR (300 MHz, CDCl3) δ: 8.93 - 8.91 (m, 1H), 8.71 - 8.69 (m, 1H), 8.20 - 8.15 (m, 2H), 7.50 - 7.45 (m, 1H), 7.40 - 7.32 (m, 1H), 6.85 (s, 1H), 2.56 (s, 3H).

[0764] Example 38: Synthesis of Compound 40 (3-methyl-1-(thiazol-2-yl)-1H-benzo[g]indazole-4,5-dione)

[0765] (1) Synthesis of 2-(5-methoxy-3-methyl-1H-benzo[g]indazol-1-yl)thiazole

[0766] Dissolve 5-methoxy-3-methyl-1H-benzo[g]indazole (1 mmol, intermediate 8), copper(I) iodide (5 mol%), N,N'-dimethylethylenediamine (10 mol%), and tripotassium phosphate (2 mmol) in DMF. Raise the temperature to 110 °C, add 2-bromothiazole (1.2 mmol), and react. Add H2O to terminate the reaction, extract the reaction solution with ethyl acetate, and remove the residual moisture in the organic layer with anhydrous magnesium sulfate. Concentrate the organic layer under reduced pressure to obtain the title compound, which is used in the next reaction without further purification of this compound.

[0767] (2) Synthesis of 3-methyl-1-(thiazol-2-yl)-1H-benzo[g]indazol-5-ol

[0768] Use 2-(5-methoxy-3-methyl-1H-benzo[g]indazol-1-yl)thiazole as the starting material and obtain the title compound according to the procedure described in (2) of Example 1, which is used in the next reaction without further purification of this compound.

[0769] (3) Synthesis of Compound 40 (3-methyl-1-(thiazol-2-yl)-1H-benzo[g]indazole-4,5-dione)

[0770] Use 3-methyl-1-(thiazol-2-yl)-1H-benzo[g]indazol-5-ol as the starting material and obtain the title compound according to the procedure described in (3) of Example 1.

[0771] Yield: 38%, yellow solid.

[0772] 1 H NMR (300 MHz, CDCl3) δ: 8.15 - 8.13 (m, 1H), 8.06 - 8.04 (m, 1H), 7.76 - 7.75 (m, 1H), 7.53 - 7.44 (m, 3H), 2.56 (s, 3H).

[0773] Example 39: Synthesis of Compound 41 (3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazole-4,5-dione) and Compound 42 (3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazole-4,5-dione)

[0774] (1) Synthesis of a mixture of 5-methoxy-3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazole and 5-methoxy-3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazole

[0775] Dissolve 5-methoxy-3-methyl-1H-benzo[g]indazole (2 mmol, Intermediate 8), copper(I) iodide (5 mol%), N,N'-dimethylethylenediamine (10 mol%), tripotassium phosphate (4 mmol), and 4-iodopyridine (2.4 mmol) in DMF. React at a temperature below 80 °C for 8 hours. Add H2O to terminate the reaction, extract the reaction solution with ethyl acetate, dry the organic layer with anhydrous magnesium sulfate, and concentrate under reduced pressure to obtain a mixture of 5-methoxy-3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazole and 5-methoxy-3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazole, which is used in the next reaction without further purification.

[0776] (2) Synthesis of a mixture of 3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazol-5-ol and 3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazol-5-ol

[0777] Use the mixture of 5-methoxy-3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazole and 5-methoxy-3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazole as the starting material and obtain the mixture of the title compounds according to the procedure described in (2) of Example 1, which is used in the next reaction without further purification.

[0778] (3) Synthesis of Compound 41 (3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazole-4,5-dione) and Compound 42 (3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazole-4,5-dione)

[0779] Use the mixture of 3-methyl-1-(pyridin-4-yl)-1H-benzo[g]indazol-5-ol and 3-methyl-2-(pyridin-4-yl)-2H-benzo[g]indazol-5-ol as the starting material and obtain the mixture of the title compounds according to the procedure described in (3) of Example 1. Separate Compound 41 and Compound 42 from this mixture.

[0780] (Compound 41) Yield: 6% overall, yellow solid.

[0781] 11H NMR (300 MHz, CDCl3) δ: 9.01 - 9.00 (m, 1H), 8.21 - 8.20 (m, 1H), 7.66 - 7.65 (m, 1H), 7.25 - 7.23 (m, 1H), 7.21 - 7.17 (m, 4H), 2.38 (s, 3H).

[0782] (Compound 42) Yield: 4% overall, yellow solid.

[0783] 1 1H NMR (300 MHz, CDCl3) δ: 8.87 - 8.85 (m, 1H), 8.19 - 8.17 (m, 1H), 8.12 - 8.10 (m, 1H), 7.73 - 7.69 (m, 1H), 7.60 - 7.59 (m, 2H), 7.55 - 7.51 (m, 1H), 2.85 (s, 3H).

[0784] Example 40: Synthesis of Compound 43 (3 - methyl - 1H - benzo[g]indazole - 4,5 - dione)

[0785] (1) Synthesis of 3 - methyl - 1H - benzo[g]indazol - 5 - ol

[0786] Using methoxy - 3 - methyl - 1H - benzo[g]indazole (Intermediate 8) as the starting material, the title compound was obtained according to the procedure described in (2) of Example 1 and was used in the next reaction without further purification.

[0787] (2) Synthesis of Compound 43 (3 - methyl - 1H - benzo[g]indazole - 4,5 - dione)

[0788] Using 3 - methyl - 1H - benzo[g]indazol - 5 - ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0789] Yield: 80%, yellow solid.

[0790] 1 1H NMR (300 MHz, DMSO - d6) δ: 13.65 (br s, 1H), 7.98 - 7.95 (m, 2H), 7.76 - 7.73 (m, 1H), 7.54 - 7.50 (m, 1H), 2.54 (s, 3H).

[0791] Example 41: Synthesis of Compound 44 (3 - methyl - 2 - (benzenesulfonyl Group ) - 2H - benzo[g]indazole - 4,5 - dione)

[0792] Dissolve 3-methyl-1H-benzo[g]indazole-4,5-dione (0.95 mmol, Compound 43) and dimethylaminopyridine (10 mol%) in dichloromethane (10 mL). While stirring, add trimethylamine (1.5 mmol) and benzenesulfonyl chloride (1.2 mmol), and react at room temperature. After the reaction is completed, add water to terminate the reaction, and extract the reaction solution with ethyl acetate. Dry the organic layer with anhydrous magnesium sulfate, concentrate under reduced pressure, and purify by column chromatography.

[0793] Yield: 28%, yellow solid.

[0794] 1 H NMR (300 MHz, DMSO-d6) δ: 8.17 - 8.12 (m, 4H), 7.74 - 7.70 (m, 2H), 7.65 - 7.61 (m, 2H), 7.57 - 7.53 (m, 1H), 3.02 (s, 3H).

[0795] Example 42: Synthesis of Compound 45 (3-methyl-2-(4-fluorobenzenesulfonyl)-2H-benzo[g]indazole-4,5-dione)

[0796] Use 3-methyl-1H-benzo[g]indazole-4,5-dione (0.95 mmol, Compound 43) and 4-fluorobenzenesulfonyl chloride (1.2 mmol) as starting materials and reactants, and obtain the title compound according to the procedure described in (1) of Example 41.

[0797] Yield: 35.2%, yellow solid.

[0798] 1 H NMR (300 MHz, CDCl3) δ: 8.19 - 8.11 (m, 4H), 7.73 - 7.69 (m, 1H), 7.56 - 7.52 (m, 1H), 7.33 - 7.30 (m, 2H), 3.02 (s, 3H).

[0799] Example 43: Synthesis of Compound 46 (2-(2-chlorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0800] Use 3-methyl-1H-benzo[g]indazole-4,5-dione (0.95 mmol, Compound 43) and 2-chlorobenzenesulfonyl chloride (1.2 mmol) as starting materials and reactants, and obtain the title compound according to the procedure described in (1) of Example 41.

[0801] Yield: 42.3%, yellow solid.

[0802] 11H NMR (300 MHz, CDCl3) δ: 8.43 - 8.41 (m, 1H), 8.16 - 8.14 (m, 1H), 7.95 - 7.93 (m, 1H), 7.68 - 7.51 (m, 5H), 3.11 (s, 3H).

[0803] Example 44: Synthesis of Compound 47 (2-(3-chlorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0804] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and 3-chlorobenzenesulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0805] Yield: 36.6%, yellow solid.

[0806] 1 1H NMR (300 MHz, CDCl3) δ: 8.17 - 8.14 (m, 2H), 8.11 - 8.10 (m, 1H), 8.02 - 8.00 (m, 1H), 7.75 - 7.68 (m, 2H), 7.59 - 7.53 (m, 2H), 3.02 (s, 3H).

[0807] Example 45: Synthesis of Compound 48 (3-methyl-2-(pyridin-3-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione)

[0808] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and pyridine-3-sulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0809] Yield: 28%, yellow solid.

[0810] 1 1H NMR (300 MHz, CDCl3) δ: 8.35 - 8.34 (m, 1H), 8.95 - 8.93 (m, 1H), 8.42 - 8.39 (m, 1H), 8.17 - 8.11 (m, 2H), 7.74 - 7.70 (m, 1H), 7.60 - 7.56 (m, 2H), 3.05 (s, 3H).

[0811] Example 46: Synthesis of Compound 49 (2-(4-chlorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0812] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.95 mmol, Compound 43) and 4-chlorobenzenesulfonyl chloride (1.2 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0813] Yield: 41%, yellow solid.

[0814] 1 H NMR (300 MHz, CDCl3) δ: 8.16 - 8.12 (m, 2H), 8.08 - 8.05 (m, 2H), 7.73 - 7.69 (m, 1H), 7.61 - 7.55 (m, 3H), 3.01 (s, 3H).

[0815] Example 47: Synthesis of Compound 50 (3-methyl-2-toluenesulfonyl-2H-benzo[g]indazole-4,5-dione)

[0816] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.95 mmol, Compound 43) and 4-toluenesulfonyl chloride (1.2 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0817] Yield: 41%, yellow solid.

[0818] 1 H NMR (300 MHz, CDCl3) δ: 8.15 - 8.13 (m, 2H), 8.01 - 7.98 (m, 2H), 7.72 - 7.68 (m, 1H), 7.55 - 7.51 (m, 1H), 7.41 - 7.39 (m, 2H), 3.00 (s, 3H), 2.45 (s, 3H).

[0819] Example 48: Synthesis of Compound 51 (2-(4-methoxybenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0820] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and 4-methoxybenzenesulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0821] Yield: 64%, yellow solid.

[0822] 11H NMR (300 MHz, CDCl3) δ: 8.15 - 8.13 (m, 2H), 8.06 - 8.03 (m, 2H), 7.72 - 7.68 (m, 1H), 7.54 - 7.50 (m, 1H), 7.07 - 7.03 (m, 2H), 3.89 (s, 3H), 3.00 (s, 3H).

[0823] Example 49: Synthesis of Compound 52 (Methyl 4-(3-methyl-4,5-dioxo-4,5-dihydro-2H-benzo[g]indazole-2-ylsulfonyl)benzoate)

[0824] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and methyl 4-(chlorosulfonyl)benzoate (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0825] Yield: 44.8%, yellow solid.

[0826] 1 1H NMR (300 MHz, CDCl3) δ: 8.27 - 8.18 (m, 4H), 8.16 - 8.12 (m, 2H), 7.73 - 7.69 (m, 1H), 7.57 - 7.53 (m, 1H), 3.96 (s, 3H), 3.02 (s, 3H).

[0827] Example 50: Synthesis of Compound 53 (2-(Cyclopropylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0828] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and cyclopropylsulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0829] Yield: 74%, yellow solid.

[0830] 1 1H NMR (300 MHz, CDCl3) δ: 8.20 - 8.16 (m, 2H), 7.75 - 7.71 (m, 1H), 7.59 - 7.55 (m, 1H), 3.07 - 3.01 (m, 1H), 2.97 (s, 3H), 1.61 - 1.58 (m, 2H), 1.32 - 1.26 (m, 2H).

[0831] Example 51: Synthesis of Compound 54 (2-(Cyclopentylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0832] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and cyclopentanesulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0833] Yield: 26.7%, yellow solid.

[0834] 1 H NMR (300 MHz, CDCl3) δ: 8.20 - 8.16 (m, 2H), 7.75 - 7.71 (m, 1H), 7.59 - 7.55 (m, 1H), 4.27 - 4.19 (m, 1H), 2.99 (s, 3H), 2.22 - 2.13 (m, 2H), 2.10 - 2.01 (m, 2H), 1.94 - 1.84 (m, 2H), 1.77 - 1.68 (m, 2H).

[0835] Example 52: Synthesis of Compound 55 (4-(3-methyl-4,5-dioxo-4,5-dihydro-2H-benzo[g]indazole-2-ylsulfonyl)benzonitrile)

[0836] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and 4-cyanobenzenesulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0837] Yield: 22.5%, yellow solid.

[0838] 1 H NMR (300 MHz, CDCl3) δ: 8.27 - 8.25 (m, 2H), 8.17 - 8.15 (m, 1H), 8.12 - 8.10 (m, 1H), 7.93 - 7.91 (m, 2H), 7.74 - 7.71 (m, 1H), 7.59 - 7.55 (m, 1H), 3.03 (s, 3H).

[0839] Example 53: Synthesis of Compound 56 (3-methyl-2-(4-nitrobenzosulfonyl)-2H-benzo[g]indazole-4,5-dione)

[0840] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.94 mmol, Compound 43) and 4-nitrobenzenesulfonyl chloride (1.13 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0841] Yield: 32%, yellow solid.

[0842] 1 H NMR (300 MHz, CDCl3) δ: 8.47 - 8.45 (m, 2H), 8.36 - 8.33 (m, 2H), 8.17 - 8.15 (m, 1H), 8.12 - 8.10 (m, 1H), 7.75 - 7.71 (m, 1H), 7.59 - 7.55 (m, 1H), 3.05 (s, 3H).

[0843] Example 54: Synthesis of Compound 57 (3 - Methyl - 2 - (4 - (trifluoromethyl)phenylsulfonyl)-2H - benzo[g]indazole - 4,5 - dione)

[0844] Using 3 - methyl - 1H - benzo[g]indazole - 4,5 - dione (0.71 mmol, Compound 43) and 4 - (trifluoromethyl)phenylsulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0845] Yield: 54.8%, yellow solid.

[0846] 1 H NMR (300 MHz, CDCl3) δ: 8.28 - 8.26 (m, 2H), 8.17 - 8.12 (m, 2H), 7.90 - 7.88 (m, 2H), 7.74 - 7.70 (m, 1H), 7.58 - 7.54 (m, 1H), 3.03 (s, 3H).

[0847] Example 55: Synthesis of Compound 58 (2 - (3,4 - Difluorophenylsulfonyl)-3 - methyl - 2H - benzo[g]indazole - 4,5 - dione)

[0848] Using 3 - methyl - 1H - benzo[g]indazole - 4,5 - dione (0.5 mmol, Compound 43) and 3,4 - difluorophenylsulfonyl chloride (0.6 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0849] Yield: 20.6%, red - yellow solid.

[0850] 1 H NMR (300 MHz, CDCl3) δ: 8.19 - 8.12 (m, 2H), 8.02 - 7.94 (m, 2H), 7.77 - 7.71 (m, 1H), 7.60 - 7.52 (m, 1H), 7.46 - 7.39 (m, 1H), 3.02 (s, 3H).

[0851] Example 56: Synthesis of Compound 59 (2-(2,4-Difluorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0852] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and 2,4-difluorobenzenesulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0853] Yield: 14.6%, yellow solid.

[0854] 1 H NMR (300 MHz, CDCl3) δ: 8.29 - 8.23 (m, 1H), 8.19 - 8.15 (m, 1H), 8.07 - 8.01 (m, 1H), 7.73 - 7.65 (m, 1H), 7.59 - 7.52 (m, 1H), 7.19 - 7.15 (m, 1H), 7.04 - 6.96 (m, 1H), 3.08 (s, 3H).

[0855] Example 57: Synthesis of Compound 60 (3-Methyl-2-(quinolin-8-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione)

[0856] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and quinoline-8-sulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0857] Yield: 30%, yellow solid.

[0858] 1 H NMR (300 MHz, CDCl3) δ: 8.90 - 8.89 (m, 1H), 8.82 - 8.80 (m, 1H), 8.25 - 8.19 (m, 2H), 8.10 - 8.08 (m, 1H), 7.93 - 7.91 (m, 1H), 7.81 - 7.77 (m, 1H), 7.56 - 7.50 (m, 2H), 7.46 - 7.44 (m, 1H), 3.40 (s, 3H).

[0859] Example 58: Synthesis of Compound 61 (3-Methyl-2-(1-methyl-1H-imidazol-2-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione)

[0860] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and 1-methylimidazole-2-sulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0861] Yield: 16%, yellow solid.

[0862] 1 H NMR (300 MHz, CDCl3) δ: 8.18 - 8.16 (m, 1H), 8.09 - 8.03 (m, 1H), 7.73 - 7.69 (m, 1H), 7.58 - 7.52 (m, 1H), 7.23 (s, 1H), 7.14 (s, 1H), 4.22 (s, 3H), 3.10 (s, 3H).

[0863] Example 59: Synthesis of Compound 62 (3-methyl-2-(morpholinosulfonyl)-2H-benzo[g]indazole-4,5-dione)

[0864] Using 3-methyl-1H-benzo[g]indazole-4,5-dione (0.71 mmol, Compound 43) and morpholine-4-sulfonyl chloride (0.85 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 41.

[0865] Yield: 23.5%, yellow solid.

[0866] 1 H NMR (300 MHz, CDCl3) δ: 8.20 - 8.18 (m, 1H), 8.10 - 8.08 (m, 1H), 7.75 - 7.72 (m, 1H), 7.58 - 7.55 (m, 1H), 3.86 - 3.84 (m, 4H), 3.62 - 3.60 (m, 4H), 2.93 (s, 3H).

[0867] Example 60: Synthesis of Compound 63 (1-benzyl-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0868] (1) Synthesis of 1-benzyl-5-methoxy-3-methyl-1H-benzo[g]indazole

[0869] Using 5-methoxy-3-methyl-1H-benzo[g]indazole (2.1 mmol, Intermediate 8) and benzyl bromide (4.2 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 20.

[0870] Yield: 45%, gray solid.

[0871] 1 1H NMR (300 MHz, CDCl3) δ: 8.38 - 8.36 (m, 1H), 8.26 - 8.24 (m, 1H), 7.54 - 7.43 (m, 2H), 7.29 - 7.21 (m, 3H), 7.11 - 7.09 (m, 2H), 6.88 (s, 1H), 5.98 (s, 2H), 4.05 (s, 3H), 2.64 (s, 3H).

[0872] (2) Synthesis of 1-benzyl-3-methyl-1H-benzo[g]indazol-5-ol

[0873] Using 1-benzyl-5-methoxy-3-methyl-1H-benzo[g]indazole as the starting material and obtaining a mixture of the title compound according to the steps described in (2) of Example 1, which was used in the next reaction without further purification of the mixture.

[0874] (3) Synthesis of compound 63 (1-benzyl-3-methyl-1H-benzo[g]indazole-4,5-dione)

[0875] Using 1-benzyl-3-methyl-1H-benzo[g]indazol-5-ol as the starting material and obtaining the title compound according to the steps described in (3) of Example 1.

[0876] Yield: 59%, yellow solid.

[0877] 1 1H NMR (300 MHz, CDCl3) δ: 8.14 - 8.12 (m, 1H), 7.52 - 7.50 (m, 2H), 7.45 - 7.30 (m, 4H), 7.15 - 7.13 (m, 2H), 5.73 (s, 2H), 2.57 (s, 3H).

[0878] Example 61: Synthesis of compound 64 (3-methyl-1-phenethyl-1H-benzo[g]indazole-4,5-dione)

[0879] (1) Synthesis of 5-methoxy-3-methyl-1-phenethyl-1H-benzo[g]indazole

[0880] Using 5-methoxy-3-methyl-1H-benzo[g]indazole (2 mmol, intermediate 8) and phenethyl bromide (4 mmol) as the starting materials and reactants, and obtaining the title compound according to the steps described in (1) of Example 20, which was used in the next reaction without further purification.

[0881] (2) Synthesis of 3-Methyl-1-phenethyl-1H-benzo[g]indazol-5-ol

[0882] Using 5-Methoxy-3-methyl-1-phenethyl-1H-benzo[g]indazole as the starting material, a mixture of the title compounds was obtained according to the steps described in (2) of Example 1 and was used in the next reaction without further purification of the mixture.

[0883] (3) Synthesis of Compound 64 (3-Methyl-1-phenethyl-1H-benzo[g]indazole-4,5-dione)

[0884] Using 3-Methyl-1-phenethyl-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the steps described in (3) of Example 1.

[0885] Yield: 20%, yellow solid.

[0886] 1 H NMR (300 MHz, CDCl3) δ: 8.21 - 8.19 (m, 1H), 7.66 - 7.61 (m, 2H), 7.52 - 7.48 (m, 1H), 7.34 - 7.30 (m, 2H), 7.25 - 7.21 (m, 3H), 4.72 - 4.68 (m, 2H), 3.30 - 3.27 (m, 2H), 2.55 (s, 3H).

[0887] Example 62: Synthesis of Compound 65 (1-(4-Fluorophenethyl)-3-methyl-1H-benzo[g]indazole-4,5-dione) and Compound 66 (2-(4-Fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0888] (1) Synthesis of a mixture of 1-(4-Fluorophenethyl)-5-methoxy-3-methyl-1H-benzo[g]indazole and 2-(4-Fluorophenethyl)-5-methoxy-3-methyl-2H-benzo[g]indazole

[0889] Using 5-Methoxy-3-methyl-1H-benzo[g]indazole (2 mmol, Intermediate 8) and 4-Fluorophenethyl bromide (4 mmol) as the starting materials and reactants, a mixture of the title compounds 1-(4-Fluorophenethyl)-5-methoxy-3-methyl-1H-benzo[g]indazole and 2-(4-Fluorophenethyl)-5-methoxy-3-methyl-2H-benzo[g]indazole was obtained according to the steps described in (1) of Example 20 and was used in the next reaction without further purification of the mixture.

[0890] (2) Synthesis of a mixture of 1-(4-fluorophenethyl)-3-methyl-1H-benzo[g]indazol-5-ol and 2-(4-fluorophenethyl)-3-methyl-2H-benzo[g]indazol-5-ol

[0891] A mixture of 1-(4-fluorophenethyl)-5-methoxy-3-methyl-1H-benzo[g]indazole and 2-(4-fluorophenethyl)-5-methoxy-3-methyl-2H-benzo[g]indazole was used as the starting material, and the mixture of the title compounds was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification of the mixture.

[0892] (3) Synthesis of compound 65 (1-(4-fluorophenethyl)-3-methyl-1H-benzo[g]indazole-4,5-dione) and compound 66 (2-(4-fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0893] A mixture of 1-(4-fluorophenethyl)-3-methyl-1H-benzo[g]indazol-5-ol and 2-(4-fluorophenethyl)-3-methyl-2H-benzo[g]indazol-5-ol was used as the starting material, and the mixture of the title compounds was obtained according to the procedure described in (3) of Example 1. Compound 65 and compound 66 were separated from this mixture.

[0894] (Compound 65) Yield: 3%, yellow solid.

[0895] 1 H NMR (300 MHz, CDCl3) δ: 8.23 - 8.21 (m, 1H), 7.67 - 7.59 (m, 2H), 7.54 - 7.50 (m, 1H), 7.18 - 7.15 (m, 2H), 7.02 - 6.98 (m, 2H), 4.70 - 4.66 (m, 2H), 3.8 - 3.25 (m, 2H), 2.55 (s, 3H).

[0896] (Compound 66) Yield: 2%, yellow solid.

[0897] 1 H NMR (300 MHz, CDCl3) δ: 8.15 - 8.13 (m, 1H), 8.06 - 8.04 (m, 1H), 7.70 - 7.66 (m, 1H), 7.49 - 7.45 (m, 1H), 7.04 - 6.94 (m, 4H), 4.30 - 4.27 (m, 2H), 3.22 - 3.19 (m, 2H), 2.22 (s, 3H).

[0898] Example 63: Synthesis of Compound 67 (3-Methyl-1-(3-phenylpropyl)-1H-benzo[g]indazole-4,5-dione)

[0899] (1) Synthesis of 5-Methoxy-3-methyl-1-(3-phenylpropyl)-1H-benzo[g]indazole

[0900] Using 5-methoxy-3-methyl-1H-benzo[g]indazole (2 mmol, Intermediate 8) and 1-bromo-3-phenylpropane (4 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 20 and used in the next reaction without further purification.

[0901] (2) Synthesis of 3-Methyl-1-(3-phenylpropyl)-1H-benzo[g]indazol-5-ol

[0902] Using 5-methoxy-3-methyl-1-(3-phenylpropyl)-1H-benzo[g]indazole as the starting material, a mixture of the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification of the mixture.

[0903] (3) Synthesis of Compound 67 (3-Methyl-1-(3-phenylpropyl)-1H-benzo[g]indazole-4,5-dione)

[0904] Using 3-methyl-1-(3-phenylpropyl)-1H-benzo[g]indazol-5-ol as the starting material, the title compound was obtained according to the procedure described in (3) of Example 1.

[0905] Yield: 32%, yellow solid.

[0906] 1 H NMR (300 MHz, CDCl3) δ: 8.13 - 8.11 (m, 1H), 7.45 - 7.43 (m, 2H), 7.36 - 7.33 (m, 2H), 7.29 - 7.20 (m, 4H), 4.46 - 4.40 (m, 2H), 2.84 - 2.80 (m, 2H), 2.50 (s, 3H), 2.31 - 2.27 (m, 2H).

[0907] Example 64: Synthesis of Compound 68 (3-Methyl-1-(4-methylphenethyl)-1H-benzo[g]indazole-4,5-dione) and Compound 69 (3-Methyl-2-(4-methylphenethyl)-2H-benzo[g]indazole-4,5-dione)

[0908] (1) Synthesis of a mixture of 5-methoxy-3-methyl-1-(4-methylphenethyl)-1H-benzo[g]indazole and 5-methoxy-3-methyl-2-(4-methylphenethyl)-2H-benzo[g]indazole

[0909] Using 5-methoxy-3-methyl-1H-benzo[g]indazole (2 mmol, Intermediate 8) and 4-methylphenethyl bromide (4 mmol) as starting materials and reactants, and obtaining the title compounds, a mixture of 5-methoxy-3-methyl-1-(4-methylphenethyl)-1H-benzo[g]indazole and 5-methoxy-3-methyl-2-(4-methylphenethyl)-2H-benzo[g]indazole, according to the procedure described in (1) of Example 20. The mixture was used in the next reaction without further purification.

[0910] (2) Synthesis of a mixture of 3-methyl-1-(4-methylphenethyl)-1H-benzo[g]indazol-5-ol and 3-methyl-2-(4-methylphenethyl)-2H-benzo[g]indazol-5-ol

[0911] Using the mixture of 5-methoxy-3-methyl-1-(4-methylphenethyl)-1H-benzo[g]indazole and 5-methoxy-3-methyl-2-(4-methylphenethyl)-2H-benzo[g]indazole as the starting material and obtaining the title compound mixture according to the procedure described in (2) of Example 1. The mixture was used in the next reaction without further purification.

[0912] (3) Synthesis of Compound 68 (3-methyl-1-(4-methylphenethyl)-1H-benzo[g]indazole-4,5-dione) and Compound 69 (3-methyl-2-(4-methylphenethyl)-2H-benzo[g]indazole-4,5-dione)

[0913] Using the mixture of 3-methyl-1-(4-methylphenethyl)-1H-benzo[g]indazol-5-ol and 3-methyl-2-(4-methylphenethyl)-2H-benzo[g]indazol-5-ol as the starting material and obtaining the title compound mixture according to the procedure described in (3) of Example 1. Compounds 68 and 69 were separated from the mixture.

[0914] (Compound 68) Yield: 10%, yellow solid.

[0915] 11H NMR (300 MHz, CDCl3) δ: 8.21 - 8.19 (m, 1H), 7.63 (s, 2H), 7.52 - 7.50 (m, 1H), 7.11 (s, 4H), 4.69 - 4.65 (m, 2H), 3.26 - 3.22 (m, 2H), 2.56 (s, 2H), 2.31 (s, 3H).

[0916] (Compound 69) Yield: 9%, yellow solid.

[0917] 1 1H NMR (300 MHz, CDCl3) δ: 8.16 - 8.13 (m, 1H), 8.07 - 8.05 (m, 1H), 7.69 - 7.67 (m, 1H), 7.46 - 7.44 (m, 1H), 7.08 - 7.05 (m, 2H), 6.95 - 6.92 (m, 2H), 4.30 - 4.26 (m, 2H), 3.19 - 3.15 (m, 2H), 2.31 (s, 3H), 2.16 (s, 3H).

[0918] Example 65: Synthesis of Compound 70 (2-(2-Fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0919] (1) Synthesis of 2-(2-Fluorophenethyl)-5-methoxy-3-methyl-2H-benzo[g]indazole

[0920] Using 5-methoxy-3-methyl-1H-benzo[g]indazole (2 mmol, Intermediate 8) and 2-fluorophenethyl bromide (4 mmol) as starting materials and reactants, the title compound was obtained according to the procedure described in (1) of Example 20 and used in the next reaction without further purification.

[0921] (2) Synthesis of 2-(2-Fluorophenethyl)-3-methyl-2H-benzo[g]indazol-5-ol

[0922] Using 2-(2-fluorophenethyl)-5-methoxy-3-methyl-2H-benzo[g]indazole as the starting material, the mixture of the title compound was obtained according to the procedure described in (2) of Example 1 and used in the next reaction without further purification of the mixture.

[0923] (3) Synthesis of Compound 70 (2-(2-Fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione)

[0924] The title compound was obtained using 2-(2-fluorophenethyl)-3-methyl-2H-benzo[g]indazol-5-ol as the starting material and following the steps described in (3) of Example 1.

[0925] Yield: 3%, yellow solid.

[0926] 1 H NMR (300 MHz, CDCl3) δ: 8.14 - 8.12 (m, 1H), 8.05 - 8.03 (m, 1H), 7.69 - 7.65 (m, 1H), 7.48 - 7.44 (m, 1H), 7.25 - 7.23 (m, 1H), 7.08 - 6.96 (m, 3H), 4.36 - 4.33 (m, 2H), 3.28 - 3.25 (m, 2H), 2.27 (s, 3H).

[0927] Experimental example

[0928] Experimental Example 1. In vitro NQO1 Enzyme Activity Test

[0929] In order to determine the NQO1 enzyme activity of the compounds synthesized in the examples, the following experiment was conducted.

[0930] After dissolving the compound of the present invention's example in DMSO to make a 10 mM stock solution, it was diluted with DMSO to a concentration of 250 μM to prepare a compound sample solution. For the experimental group, the previously prepared compound sample solution was added to the enzyme reaction solution, which was prepared by adding 50 μl of a 1.54 mM cytochrome C solution to 900 μl of a 50 mM Tris-HCl (pH 7.5) solution containing 0.14% BSA. For the negative control group, DMSO without the compound of the present invention was added to the same enzyme reaction solution. For each experimental group and negative control group, after adding 20 μl of 100 ng / mL NQO1 protein, 10 μl of a 20 mM NADH solution was added to make the total volume reach 1 mL, and the absorbance change was measured at a wavelength of 550 nm for 10 minutes using a 1 mL cuvette. As cytochrome C was reduced at 550 nm within 10 minutes, the reaction kinetics was measured by the increase in absorbance. The absorbance value was obtained, and thus, the NQO1 activity of the compound of the present invention was expressed as the amount of reduced cytochrome C (nmol of reduced cytochrome C / min / μg of NQO1 protein).

[0931] Absorbance coefficient of cytochrome C: 21.1 (μmol / mL) -1 cm -1

[0932] BSA: Bovine Serum Albumin

[0933] Tris-HC: Tris(hydroxymethyl)aminomethane hydrochloride (buffer solution)

[0934] Equipment = Cary 100 UV-Visible Spectrophotometer

[0935] The results are shown in Tables 1 to 8 below.

[0936] Table 1

[0937]

[0938]

[0939] Table 2

[0940]

[0941] Table 3

[0942]

[0943] Table 4

[0944]

[0945] Table 5

[0946]

[0947] Table 6

[0948]

[0949] Table 7

[0950]

[0951] Table 8

[0952]

[0953] As shown in Tables 1 to 8 above, when treated with the compound of the present invention (experimental group), the amount of reduced cytochrome C was increased compared to the untreated case (negative control group), thereby confirming that the compound of the present invention is used as a substrate for NQO1 to activate the redox reaction of NQO1.

Claims

1. A compound represented by the following Chemical Formula 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof: Chemical Formula 1 In the formula, R1 is H or a halogen; R2 does not exist, or is selected from the group consisting of H, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 6-10 aryl, and substituted or unsubstituted heteroaryl; R3 is absent or is selected from the group consisting of substituted or unsubstituted C 1-10 alkyl, unsubstituted heteroaryl, and -S(O)(O)R5; provided that R2 and R3 are not both absent and are not both an alkyl group or a heteroaryl group at the same time; R4 is selected from the group consisting of H, substituted or unsubstituted C 1-10 alkyl, and substituted or unsubstituted C 6-10 aryl; X1 and X4 are carbon atoms, and X2 and X3 are nitrogen atoms; is a single bond or a double bond, depending on R1, R2, R3, X1, X2, X3 and X4; and is absent or is a single bond, depending on X1, X2, X3 and X4; The alkyl group is a straight-chain, branched-chain or cyclic hydrocarbon group, and can contain at least one double bond or triple bond in the hydrocarbon chain. When the alkyl group is substituted, its substituents are selected from the group consisting of halogen, C 1-6 alkoxy, substituted or unsubstituted C 6-10 aryl, heteroaryl and -NR6R7; When the aryl or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)OR5, and C 1-6 alkyl substituted with one, two, or three halogens; R5 is selected from the group consisting of H, C 1-6 alkyl, unsubstituted C 3-6 cycloalkyl, unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; R6 and R7 are each independently H or C 1-6 alkyl; The aryl is a C 6-10 aromatic ring, the heterocyclic group is a 3- to 7-membered heterocyclic group having at least one heteroatom selected from N, O, and S in the ring, and the heteroaryl is a 5- to 10-membered heteroaromatic ring having at least one heteroatom selected from N, O, and S in the ring.

2. The compound according to claim 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof, characterized in that R2 is absent or is selected from the group consisting of H, unsubstituted C 1-10 alkyl, substituted or unsubstituted C 6-10 aryl, and substituted or unsubstituted heteroaryl, wherein when the aryl or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, halogen, and -C(O)OR5; R3 is absent or is an unsubstituted C 1-10 alkyl, unsubstituted heteroaryl; provided that R2 and R3 are not both absent and are not both an alkyl group or a heteroaryl group at the same time; R4 is selected from the group consisting of H, substituted or unsubstituted C 1-10 alkyl, and substituted or unsubstituted C 6-10 aryl, wherein when the alkyl is substituted, the substituent is selected from the group consisting of halogen, C 1-6 alkoxy, unsubstituted C 6-10 aryl, heteroaryl, and -NR6R7, and when the aryl is substituted, the substituent is halogen; R5, R6, and R7 are each independently H or C 1-6 alkyl group.

3. The compound according to claim 2, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof, characterized in that the aryl group is a phenyl group or a naphthyl group, and the heteroaryl group is a pyridyl group, a pyridazinyl group, a pyrrolyl group, a pyrazolyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group or a furyl group.

4. The compound according to claim 3, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof, characterized in that, The compound is selected from the group consisting of the following compounds: 3-Methyl-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-Isopropyl-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-Heptyl-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-Phenethyl-1-phenyl-1H-benzo[g]indazole-4,5-dione; 1,3-Diphenyl-1H-benzo[g]indazole-4,5-dione; 3-(4-Fluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-(3,4-Difluorophenyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-(Bromomethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-((Dimethylamino)methyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-(Methoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione; 3-(Isopropoxymethyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione; 1-Isopropyl-3-methyl-1H-benzo[g]indazole-4,5-dione; 2-Isopropyl-3-methyl-2H-benzo[g]indazole-4,5-dione; 1,3-Dimethyl-1H-benzo[g]indazole-4,5-dione; 2,3-Dimethyl-2H-benzo[g]indazole-4,5-dione; 3-((1H-Imidazol-1-yl)methyl)-1-phenyl-1H-benzo[g]indazole-4,5-dione; 1-(4-Fluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 1-(4-Chlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 1-(3,5-Difluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 1-(2,4-Dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 3-Methyl-1-p-tolyl-1H-benzo[g]indazole-4,5-dione; 3-Methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole-4,5-dione; 3-Methyl-1-(pyridin-3-yl)-1H-benzo[g]indazole-4,5-dione; 1-(2,4-Difluorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 1-Phenyl-1H-benzo[g]indazole-4,5-dione; 1-Phenyl-3-(trifluoromethyl)-1H-benzo[g]indazole-4,5-dione; 7-Fluoro-3-methyl-1-phenyl-1H-benzo[g]indazole-4,5-dione; 1-(3,5-Dichlorophenyl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 4-(3-Methyl-4,5-dioxo-4,5-dihydro-1H-benzo[g]indazol-1-yl)benzoic acid; 3-Methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole-4,5-dione; 1-(5-Chloropyridin-3-yl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 3-Methyl-1-(thiazol-2-yl)-1H-benzo[g]indazole-4,5-dione; 3-Methyl-1-(pyridin-4-yl)-1H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(pyridin-4-yl)-2H-benzo[g]indazole-4,5-dione; and 3-Methyl-1H-benzo[g]indazole-4,5-dione.

5. The compound according to claim 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof, characterized in that, R2 and R3 each independently do not exist or are a substituted alkyl group, provided that R2 and R3 do not both not exist or are not both alkyl groups at the same time, and the substituent of the alkyl group is an unsubstituted C 6-10 aryl group or a C 1-6 alkyl group or a C 6-10 aryl group substituted by an alkyl group or a halogen; R4 is an unsubstituted C 1-10 alkyl group.

6. The compound according to claim 5, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof, characterized in that, The aryl is phenyl or naphthyl.

7. The compound according to claim 6, or a pharmaceutically acceptable salt, enantiomer, diastereoisomer or tautomer thereof, characterized in that, The compound is selected from the group consisting of the following compounds: 1-Benzyl-3-methyl-1H-benzo[g]indazole-4,5-dione; 3-Methyl-1-phenethyl-1H-benzo[g]indazole-4,5-dione; 1-(4-Fluorophenethyl)-3-methyl-1H-benzo[g]indazole-4,5-dione; 2-(4-Fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 3-Methyl-1-(3-phenylpropyl)-1H-benzo[g]indazole-4,5-dione; 3-Methyl-1-(4-methylphenethyl)-1H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(4-methylphenethyl)-2H-benzo[g]indazole-4,5-dione; and 2-(2-Fluorophenethyl)-3-methyl-2H-benzo[g]indazole-4,5-dione.

8. The compound according to claim 1, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof, characterized in that, R2 is absent; R3 is -S(O)(O)R5; R4 is an unsubstituted C 1-10 alkyl group; R5 is selected from the group consisting of C 1-6 alkyl, unsubstituted C 3-6 cycloalkyl, unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; and Wherein, When the aryl or heteroaryl is substituted, its substituents are independently selected from the group consisting of C 1-6 alkyl C 1-6 alkoxy, halogen, nitro, cyano, -C(O)OR9, and C 1-6 alkyl substituted with one, two or three halogens, wherein R9 is C 1-6 alkyl.

9. The compound according to claim 8, or a pharmaceutically acceptable salt, enantiomer, diastereomer or tautomer thereof, characterized in that, The aryl is phenyl or naphthyl; the heteroaryl is pyridyl, pyridazinyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl or furyl; and the heterocyclic group is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl.

10. The compound according to claim 9, or a pharmaceutically acceptable salt, enantiomer, diastereoisomer or tautomer thereof, characterized in that, The compound is selected from the group consisting of the following compounds: 3-Methyl-2-(benzenesulfonyl)-2H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(4-fluorobenzenesulfonyl)-2H-benzo[g]indazole-4,5-dione; 2-(2-Chlorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 2-(3-Chlorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(pyridin-3-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione; 2-(4-Chlorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(toluenesulfonyl)-2H-benzo[g]indazole-4,5-dione; 2-(4-Methoxybenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; Methyl 4-(3-methyl-4,5-dioxo-4,5-dihydro-2H-benzo[g]indazol-2-ylsulfonyl)benzoate; 2-(Cyclopropylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 2-(Cyclopentylsulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 4-(3-Methyl-4,5-dioxo-4,5-dihydro-2H-benzo[g]indazol-2-ylsulfonyl)benzonitrile; 3-Methyl-2-(4-nitrobenzenesulfonyl)-2H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(4-(trifluoromethyl)benzenesulfonyl)-2H-benzo[g]indazole-4,5-dione; 2-(3,4-Difluorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 2-(2,4-Difluorobenzenesulfonyl)-3-methyl-2H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(quinolin-8-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione; 3-Methyl-2-(1-methyl-1H-imidazol-2-ylsulfonyl)-2H-benzo[g]indazole-4,5-dione; and 3-Methyl-2-(morpholinesulfonyl)-2H-benzo[g]indazole-4,5-dione.

11. A compound represented by the following Chemical Formula 2, or a salt, enantiomer, diastereomer or tautomer thereof: Chemical Formula 2 In the formula, R1 is H or halogen; R2 does not exist, or is selected from the group consisting of H, substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 6-10 aryl, and substituted or unsubstituted heteroaryl; R3 is absent or is selected from the group consisting of substituted or unsubstituted C 1-10 alkyl, unsubstituted heteroaryl, and -S(O)(O)R5; provided that R2 and R3 are not simultaneously absent and are not simultaneously alkyl or heteroaryl; R4 is selected from the group consisting of H, substituted or unsubstituted C 1-10 alkyl, and substituted or unsubstituted C 6-10 aryl; X1 and X4 are carbon atoms, and X2 and X3 are nitrogen atoms; is a single bond or a double bond, depending on R1, R2, R3, X1, X2, X3 and X4; Absent or a single bond, depending on X1, X2, X3 and X4; The alkyl group is a straight-chain, branched-chain or cyclic hydrocarbon and may contain at least one double bond or triple bond in the hydrocarbon chain. When the alkyl group is substituted, its substituents are selected from the group consisting of halogen, C 1-6 alkoxy, substituted or unsubstituted C 6-10 aryl and -NR6R7; When the aryl or heteroaryl is substituted, the substituents are independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, nitro, -C(O)OR5, and C 1-6 alkyl substituted with one, two, or three halogens; R5 is selected from the group consisting of H, C 1-6 alkyl, unsubstituted C 3-6 cycloalkyl, unsubstituted C 2-5 heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; R6 and R7 are each independently H or C 1-6 alkyl; R8 is C 1-6 alkyl or C 1-6 alkoxy-substituted C 1-6 alkyl; and The aryl is C 6-10 aryl ring, the heteroaryl group is a 3- to 7-membered heteroaryl group having at least one heteroatom selected from N, O, and S in the ring, and the heteroaryl is a 5- to 10-membered heteroaryl ring having at least one heteroatom selected from N, O, and S in the ring.

12. The compound according to claim 11, or a salt, enantiomer, diastereomer or tautomer thereof, characterized in that, The compound is selected from the group consisting of the following compounds: 5-Methoxy-3-methyl-1-phenyl-1H-benzo[g]indazole; (5-Methoxy-1-phenyl-1H-benzo[g]indazol-3-yl)methanol; 3-(Bromomethyl)-5-(methoxymethoxy)-1-phenyl-1H-benzo[g]indazole; 5-Methoxy-3-methyl-1H-benzo[g]indazole; 1-(4-Fluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole; 1-(4-Chlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole; 1-(3,5-Difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole; 1-(2,4-Dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole; 5-Methoxy-3-methyl-1-p-tolyl-1H-benzo[g]indazole; 5-Methoxy-3-methyl-1-(pyridin-2-yl)-1H-benzo[g]indazole; 5-Methoxy-3-methyl-1-(pyridin-3-yl)-1H-benzo[g]indazole; 1-(2,4-Difluorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole; 5-Methoxy-1-phenyl-1H-benzo[g]indazole; 5-Methoxy-1-phenyl-3-(trifluoromethyl)-1H-benzo[g]indazole; 7-Fluoro-5-methoxy-3-methyl-1-phenyl-1H-benzo[g]indazole; 1-(3,5-Dichlorophenyl)-5-methoxy-3-methyl-1H-benzo[g]indazole; methyl 4-(5-methoxy-3-methyl-1H-benzo[g]indazol-1-yl)benzoate; 5-methoxy-3-methyl-1-(naphthalen-1-yl)-1H-benzo[g]indazole; and 1-(5-chloropyridin-3-yl)-5-methoxy-3-methyl-1H-benzo[g]indazole.

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