A benz[b]thiophene derivative containing a sulfonamide unit, a preparation method and application thereof

Abstract

The present application relates to a kind of benz [b] thiophene derivatives containing sulfonamide unit, its preparation method and application.The compound of the present application has the following formula (I) structure, by the anti-plant virus activity test to the series derivatives, prove that it has excellent inhibitory activity to plant virus such as potato Y virus, can be used as the drug or medicament for preventing and treating plant virus disease such as potato Y virus disease.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical industry and pesticides, in particular to benz[b]thiophene derivatives containing sulfamide units and a preparation method thereof, and the application of the benz[b]thiophene derivatives containing sulfamide units as a medicine for preventing and treating plant virus diseases such as potato virus Y. BACKGROUND

[0002] Plant virus disease is a world-class plant protection problem, and is also known as "plant cancer". As the second largest plant disease, plant virus disease causes economic losses of more than 15 billion US dollars worldwide each year. Among them, potato virus Y has strong specialization, great harm, and is difficult to prevent and control, and has become the most serious plant pathogen that harms potatoes, cucumbers, tomatoes and other crops, seriously affecting China's food security. In actual production and planting, once crops are infected with the virus, the yield can be reduced by more than 80%, and even absolute yield and absolute yield can occur. In recent years, plant protection workers have carried out a large amount of development of antiviral agents, among which representative antiviral agents include anilin, ningnanmycin, morpholinium hydrochloride, lentinan and aminosugar, etc. However, due to the problems of phytotoxicity, easy resistance, short effective period, low prevention effect and high cost, the application of these agents in the field is limited, and they cannot be widely promoted.

[0003] As one of the superior structures of drug discovery, benz[b]thiophene skeleton has quite extensive biological activity and pharmacological activity, and can play the roles of antiviral, antibacterial, anticancer, anti-inflammatory, etc. It has been one of the most important lead structures in drug discovery and innovation, and is a hot spot of new drug research. In recent years, benz[b]thiophene derivatives have been widely used in the research of antiviral activity. In the field of medicine, benz[b]thiophene derivatives have wide activities of resisting HIV, hepatitis C virus, herpes virus and influenza virus, etc. In the field of pesticides, benz[b]thiophene and its related isoster series of derivatives are reported to have excellent activities of resisting tobacco mosaic virus and tomato spotted wilt virus.

[0004] In 2001, Krasutsky et al. (Krasutsky, A.; Tada, H.; Cho, H.; Hamilton, H. W.; Weber, P. C.; Gogliotti, R. D.; Nakamura, T. Diazepinoes as antiviral agents [P]. US2004116410A1, 2004.) synthesized and reported a series of benz[b]thiophene diazepine derivatives, and evaluated the activities of the compounds in treating and preventing herpes virus infection by "AVUS" screening method. The activity screening results showed that the EC 50with a value of 0.002 nM, significantly better than the control drug acyclovir (EC 50 = 1.0 nM).

[0005] In 2013, the applicant's team Hu Duyu et al. (Zhang, P.; Tang, C.; Chen, Z.; Wang, B.; Wang, X.; Jin, L. H.; Hu, D. Y. Design, synthesis, and antiviral activity of a-aminophosphonates bearing a benzothiophene moiety [J]. Phosphorus & Sulfur & the Related Elements. 2014, 189 (4): 530-540.) synthesized and reported a series of α-aminophosphonate derivatives containing a benz[b] thiophene moiety. The inhibitory activity of the compounds on tobacco mosaic virus was determined by the half-leaf spot method. The biological assay results showed that the therapeutic activity of the compound on tobacco mosaic virus was 48.1% at a concentration of 500 μg / mL, which was comparable to the activity of the positive control drug nisin (51.9%).

[0006] In 2014, Ai et al. (Ai, T.; Xu, Y.; Qiu, L.; Geraghty, R. J.; Chen, L. Hydroxamic acids block replication of hepatitis C virus [J]. J Med Chem. 2015, 58 (2): 785-800.) synthesized and reported a series of novel benz[b] thiophene-2-hydroxamic acid derivatives. The anti-hepatitis C virus replication activity was tested under the conditions of luciferase, and the activity screening results showed that the EC 50 of the compound was 0.61 μM, showing excellent anti-hepatitis C virus activity.

[0007] In 2018, Wu Shuwen et al. (Wu Shuwen, Zhou Haibing, Lan Ke, Yu Yongshi. A benzene sulfonamide compound and its application in preparing anti-influenza A virus drugs [P]. CN108129454B, 2018.) synthesized and reported a series of benzene sulfonamide derivatives containing a benz[b] thiophene moiety, and found that the benzene sulfonamide compounds could be used to prepare anti-influenza A virus drugs through in vitro anti-influenza A virus activity experiments. The EC 50 of the compound was 0.472 μM, which was comparable to the positive control drug amantadine (EC 50 = 0.425 μM).

[0008] In 2019, Zhejiang Li'En Biotechnology Co., Ltd. Guo Hongliang et al. (Guo Hongliang, Ye Zhen, Ye Xin, Zhuang Xiuyuan, Wang Xuan. A drug for treating influenza virus infection [P]. CN110922396A, 2020.) synthesized a series of drugs containing benzene[b] thiophene structure for treating influenza virus infection, and tested the inhibitory effect of the compounds on influenza virus by in vitro non-therapeutic and non-diagnostic methods. Among them, the inhibition rate of the compound reached 85.2%, which was comparable to the inhibition rate of the positive control drug ribavirin (93.8%).

[0009] In 2021, Liu Xinwen et al. (Liu Xinwen, Ju Han, Zhan Peng, Hou Lingxin, Zhang Ying. An oseltamivir derivative targeting 150-cavity and its preparation method and application [P]. CN113214105A, 2021.) synthesized and reported a series of dibenzo[b] thiophene derivatives, and tested the inhibitory activity of oseltamivir derivatives targeting 150-cavity on influenza virus. Among them, the half maximal inhibitory concentration IC 50 of the compound against various subtypes of influenza virus was less than 100 nM, which was comparable to the positive drug oseltamivir.

[0010] In 2022, the applicant's team Song Baoan et al. (Wang, Y. J.; Luo, Y. Q.; Hu, D. Y.; Song, B. A. Design, synthesis, anti-tomato spotted wilt virus activity, and mechanism of action of thienopyrimidine-containing dithioacetal derivatives [J]. J Agri Food Chem. 2022, 70(20): 6015-6025.) prepared a series of dithioacetal substituted derivatives with thieno[2,3-d]pyrimidine as the parent compound, and tested their anti-tomato spotted wilt virus activity. The results of biological activity test showed that the compounds had good anti-tomato spotted wilt virus activity, and their treatment, protection and passivation activities were 63.0, 56.6 and 74.1%, respectively. The EC 50 values of their protection activity and passivation were 252.8 and 113.5 μg / mL, respectively, which were comparable to ningnanmycin (284.8 and 144.7 μg / mL) and vanillyl thioacetal (624.9 and 300.0 μg / mL).

[0011] In summary, the small molecule drugs containing benz [b] thiophene structure generally have high and broad spectrum of antiviral activity. At present, the relevant literatures and patents mainly focus on the antiviral activity in the field of medicine, and the reports on the antiviral research of the series of derivatives on potato virus, tomato spotted wilt virus and tobacco mosaic virus are less in the field of pesticides. At present, chemical agents are the main means for plant protection, but the small molecule drugs obtained by chemical synthesis, natural product separation and other means on the current market have not ideal prevention and control effect on plant viral diseases. Therefore, it is of great significance to develop new efficient and low-risk anti-plant viral agents with benz [b] thiophene as the parent compound to solve the current prevention and control problems in production. SUMMARY

[0012] One of the purposes of the present application is to provide a kind of benz [b] thiophene derivative containing sulfonamide unit and a preparation method thereof.

[0013] Another purpose of the present application is to provide a composition containing the above-mentioned compound or its stereoisomer, or its salt or its solvate.

[0014] Another purpose of the present application is to provide the use of the above-mentioned compound or its stereoisomer, or its salt or its solvate, or the composition.

[0015] Another purpose of the present application is to provide a method for preventing and controlling agricultural pests and diseases by using the above-mentioned compound or its stereoisomer, or its salt or its solvate, or the composition.

[0016] The benz [b] thiophene derivative containing sulfonamide unit of the present application has the general structure (I) as follows:

[0017] To achieve the above-mentioned purposes, the present application adopts the following technical solutions:

[0018]

[0019] In the formula:

[0020] R 1 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, thiol, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl, and optionally substituted or unsubstituted aryl; R 2 is independently selected from one or more of hydrogen, deuterium, halogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, and optionally substituted or unsubstituted cycloalkyl; R 3one or more independently selected from any substituted or unsubstituted alkyl, any substituted or unsubstituted alkenyl, any substituted or unsubstituted cycloalkyl, any substituted or unsubstituted aryl, any substituted or unsubstituted heteroaryl, any substituted or unsubstituted benzyl.

[0021] Preferably, R 1 one or more independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, cyano, amino, thiol, carboxyl, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6alkenyl, substituted or unsubstituted C6-C 15 substituted or unsubstituted C3-C6heteroaryl; the substitution means optionally substituted with one or more of halogen, nitro, hydroxyl, cyano, amino, thiol, carboxyl, C1-C6alkyl; 2 one or more independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6alkenyl; R 3 one or more independently selected from substituted or unsubstituted C1-C 12 alkyl, substituted or unsubstituted C1-C6alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted C6-C 15 substituted or unsubstituted C3-C6heteroaryl; the substitution means optionally substituted with one or more of halogen, nitro, hydroxyl, cyano, amino, thiol, carboxyl, C1-C6alkyl;

[0022] More preferably, R 1 one or more independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, cyano, amino, thiol, carboxyl, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, iso-butyl, phenyl, benzyl, pyridyl, dioxazolyl; R 2 one or more independently selected from hydrogen, deuterium, methyl; R 3 one or more independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, iso-butyl, n-pentyl, iso-pentyl, hexyl, heptyl, octyl, cyclopropanyl, cyclohexan, morpholinyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrrolyl, furanyl, thienyl, thiazolyl, benzopyrrolyl, pyridazin, pyrimidin, pyrazin, vinyl, amino, methylamino, dimethylamino, ethylamino,

[0023] Preferred compounds are the following compounds I1-I54:

[0024] Compound I1: N-(4-((4-methylphenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0025] Compound I2: N-(4-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0026] Compound I3: N-(4-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0027] Compound I4: N-(4-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0028] Compound I5: N-(4-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0029] Compound I6: N-(4-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0030] Compound I7: N-(4-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0031] Compound I8: N-(4-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0032] Compound I9: N-(4-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0033] Compound I10: N-(4-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0034] Compound I11: N-(4-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0035] Compound I12: N-(4-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0036] Compound I13: N-(4-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0037] Compound 114: N-(4-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0038] Compound 115: N-(4-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0039] Compound 116: N-(4-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0040] Compound 117: N-(4-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0041] Compound 118: N-(4-((phenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0042] Compound 119: N-(3-((4-methylphenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0043] Compound 120: N-(3-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0044] Compound 121: N-(3-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0045] Compound 122: N-(3-((phenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0046] Compound 123: N-(3-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0047] Compound 124: N-(3-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0048] Compound 125: N-(3-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0049] Compound 126: N-(3-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0050] Compound I27: N-(3-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0051] Compound I28: N-(3-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0052] Compound I29: N-(3-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0053] Compound I30: N-(3-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0054] Compound I31: N-(3-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0055] Compound I32: N-(3-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0056] Compound I33: N-(3-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0057] Compound I34: N-(3-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0058] Compound I35: N-(3-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0059] Compound I36: N-(3-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0060] Compound I37: N-(2-((4-methylphenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0061] Compound I38: N-(2-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0062] Compound 139: N-(2-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0063] Compound 140: N-(2-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0064] Compound 141: N-(2-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0065] Compound 142: N-(2-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0066] Compound 143: N-(2-((phenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0067] Compound 144: N-(2-((phenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0068] Compound 145: N-(2-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0069] Compound 146: N-(2-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0070] Compound 147: N-(2-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0071] Compound 148: N-(2-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0072] Compound 149: N-(2-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0073] Compound 150: N-(2-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0074] Compound 151: N-(2-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0075] Compound I52: N-(2-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0076] Compound I53: N-(2-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0077] Compound I54: N-(2-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide;

[0078]

[0079] Most preferably, specifically comprising:

[0080]

[0081] The present application also provides a composition containing the compound or its stereoisomer, or its salt or its solvate, and an agriculturally acceptable adjuvant or a bactericide, a pesticide or a herbicide; preferably, the dosage form of the composition is selected from the group consisting of an emulsifiable concentrate (EC), a powder (DP), a wettable powder (WP), a granule (GR), an aqueous solution (AS), a suspension concentrate (SC), an ultra-low volume spray (ULV), a soluble powder (SP), a microcapsule (MC), a smoke (FU), an emulsion (EW), a water dispersible granule (WG).

[0082] The use of the compound or its stereoisomer, or its salt or its solvate, or the composition in the prevention and treatment of agricultural pests, preferably the agricultural pests are plant viral diseases; more preferably, the agricultural pests are potato Y virus.

[0083] The present application provides a method for preventing and treating agricultural pests, wherein the compound or its stereoisomer, or its salt or its solvate, or the composition thereof acts on the pests or their living environment; preferably, the agricultural pests are plant viral diseases; more preferably, the agricultural pests are potato Y virus.

[0084] The term "alkyl" used herein includes branched and straight chain saturated hydrocarbon groups having the indicated number of carbon atoms. For example, "C 1-10 alkyl" (or alkylene) groups are intended to include C1, C2, C3, C4, C5, C6, C7, C8, C9, and C 10 alkyl groups. In addition, for example, "C 1-6"Alkyl" means an alkyl group having from 1 to 6 carbon atoms. The alkyl group can be unsubstituted or substituted such that one or more of its hydrogen atoms are replaced by other chemical groups. Examples of alkyl groups include, but are not limited to, methyl (e.g., monofluoromethyl, difluoromethyl, and trifluoromethyl), ethyl, propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl), and the like.

[0085] "Alkenyl" is a hydrocarbon that includes both straight chain and branched chain structures and has one or more carbon-carbon double bonds occurring at any stable point in the chain. For example, "C 2-6 "Alkenyl" (or alkenylene) is intended to include C2, C3, C4, C5, and C6 alkenyl groups. Examples of alkenyl groups include, but are not limited to, ethenyl, 1- propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, and the like.

[0086] The term "cycloalkyl" refers to cycloalkyl groups, including mono-, bi- or polycyclic ring systems. C 3-7 C3, C4, C5, C6, and C7 cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. As used herein, "carbocyclic" or "carbocyclic ring" means any stable 3-, 4-, 5-, 6-, or 7-membered monocyclic ring or 7-, 8-, 9-, 10-, 11-, 12-, or 13-membered bicyclic or tricyclic ring which can be saturated, partially unsaturated, unsaturated, or aromatic. Examples of such carbocyclic rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, pentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadiene, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, anthryl, and tetrahydronaphthyl (tetrahydronaphthalenyl). As noted above, bridged rings are also included within the definition of carbocyclic rings (e.g., [2.2.2]bicyclooctane). If not otherwise specified, the preferred carbocyclic rings are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. When the term "carbocyclic" is used, it is intended to include "aryl." A bridge is a one or two carbon atom linkage between one or more carbon atoms that are not adjacent. Preferably, the bridge is one or two carbon atoms. It is noted that a bridge always converts a monocyclic ring into a bicyclic ring. When the ring is bridged, substituents on the ring are also present on the bridge.

[0087] The term "aryl" means a monocyclic or bicyclic aromatic hydrocarbon group having from 6 to 12 carbon atoms in the ring portions, such as phenyl and naphthyl, each of which can be substituted.

[0088] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine and iodine.

[0089] The term "heteroaryl" refers to substituted and unsubstituted aromatic 5- or 6-membered monocyclic groups, 9- or 10-membered bicyclic groups, and 11- to 14- membered tricyclic groups, having at least one heteroatom (O, S, or N) in at least one ring, with the heteroatom-containing rings preferably having 1, 2, or 3 heteroatoms selected from O, S, and N. Each ring of the heteroaryl group containing a heteroatom can contain one or two oxygen or sulfur atoms and / or from 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less, and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups can contain only carbon atoms and can be saturated, partially saturated, or unsaturated. Nitrogen and sulfur atoms can be optionally oxidized and nitrogen atoms can be optionally quaternized. The bicyclic or tricyclic heteroaryl must include at least one fully aromatic ring, but the other fused rings can be aromatic or nonaromatic. The heteroaryl group can be attached at any available nitrogen or carbon atom of any ring. When valence permits, the additional ring, if it is a cycloalkyl or heterocycloalkyl, is additionally optionally substituted with =0 (oxo). DETAILED DESCRIPTION

[0090] The application is further described in the following examples. It should be understood that the examples are merely for illustration of the application and should not be taken as limiting the application. Simple modifications to the preparation methods of the application within the concept of the application are intended to be within the scope of the application. All the raw materials and solvents used in the examples are commercially available reagents of corresponding purity.

[0091] Example 1: Synthesis of N-(4-((4-methylphenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (II):

[0092] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0093] Ethyl mercaptoacetate (5.75 mmol, 630.83 μL) was added dropwise to a solution of 2-chloro-5-trifluoromethylbenzaldehyde (4.79 mmol, 1.00 g) and anhydrous potassium carbonate (5.75 mmol, 795.18 mg) in DMF at 0 °C. After stirring the reaction at 0 °C for 30 minutes, the reaction was warmed to 60 °C for 12 hours. The reaction was checked by thin layer chromatography and after the completion of the reaction, the solution was filtered to remove the precipitate. The filtrate was concentrated under reduced pressure. The reaction mixture was extracted with ethyl acetate and the organic phase was washed with saturated brine. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the product.

[0094] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0095] Anhydrous lithium hydroxide (458.41 mg, 19.14 mmol) was added dropwise to a solution of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate (1.05 g, 3.83 mmol) in methanol at room temperature. After 12 hours of reaction at room temperature, the reaction was checked by thin layer chromatography. After the reaction was completed, the reaction system was concentrated under vacuum, dissolved in water, and acidified with dilute hydrochloric acid. When the pH was 6, a large amount of white precipitate was precipitated. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated brine. The organic layers were combined and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to obtain the product.

[0096] (3) Synthesis of N-(4-aminophenyl)-4-methylbenzenesulfonamide:

[0097] P-phenylenediamine (300 mg, 2.77 mmol) was dissolved in 15 mL of dichloromethane, and triethylamine (280 mg, 2.77 mmol) was added. 4-Methoxybenzenesulfonyl chloride (573 mg, 2.77 mmol) was dissolved in 5 mL of dichloromethane and added dropwise to the above solution in an ice bath. After the addition was complete, the reaction was allowed to react at room temperature. The reaction was checked by thin layer chromatography. After the starting material was completely reacted, the dichloromethane was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target compound.

[0098] (4) Synthesis of N-(4-((4-methylphenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0099] 5-Trifluoromethylbenzo[b]thiophene-2-carboxylic acid (246.20 mg, 1 mmol), N-(4-aminophenyl)-4-methylbenzenesulfonamide (262.33 mg, 1 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (570.35 mg, 1.5 mmol) were dissolved in 20 mL of DMF. After the reaction was stirred uniformly, N,N-diisopropylethylamine (435.47 μL, 2 mmol) was slowly added dropwise. The reaction was carried out at room temperature. The reaction was checked by thin layer chromatography. After the starting material was completely reacted, the system was saturated with brine, stirred, and allowed to stand. The white solid precipitated was suction filtered and dried. The crude product was purified by silica gel column chromatography, and recrystallized using an ethanol and water system to obtain the target compound. White solid 236 mg, yield 48.56%.

[0100] Example 2: Synthesis of N-(4-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I2):

[0101] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0102] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0103] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0104] Synthesized as in the method and conditions of Example 1(2), except that ethyl 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylate was used as the starting material;

[0105] (3) Synthesis of N-(4-aminophenyl)-4-methylbenzenesulfonamide:

[0106] Synthesized as in the method and conditions of Example 1(3);

[0107] (4) Synthesis of N-(4-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0108] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid was used as the starting material;

[0109] Example 3: Synthesis of N-(4-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I3):

[0110] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0111] Synthesized as in the method and conditions of Example 1(1);

[0112] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0113] Synthesized as in the method and conditions of Example 1(2);

[0114] (3) Synthesis of N-(4-aminophenyl)-2-bromobenzenesulfonamide:

[0115] Synthesized as in the method and conditions of Example 1(3), except that 2-bromobenzenesulfonyl chloride was used as the starting material;

[0116] (4) Synthesis of N-(4-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0117] Synthesized as in the method and conditions of Example 1(4), except that N-(4- aminophenyl)-2-bromobenzenesulfonamide was used as the starting material;

[0118] Example 4: Synthesis of N-(4-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (Ⅰ4):

[0119] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0120] The synthesis is performed as described in Example 1(1), except that 2-chloro-5-trifluoromethylacetophenone is used as the raw material.

[0121] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0122] The synthesis was performed as described in Example 1(2), except that ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate was used as the raw material.

[0123] (3) Synthesis of N-(4-aminophenyl)-2-bromobenzenesulfonamide:

[0124] The synthesis is performed as described in Example 1(3), except that 2-bromobenzenesulfonyl chloride is used as the raw material.

[0125] (4) Synthesis of N-(4-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0126] The synthesis was performed as described in Example 1(4), except that 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(4-aminophenyl)-2-bromobenzenesulfonamide were used as raw materials.

[0127] Example 5: Synthesis of N-(4-((4-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (Ⅰ5):

[0128] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0129] As in Example 1(1), the method and conditions for synthesis;

[0130] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0131] As in Example 1(2), the method and conditions for synthesis;

[0132] (3) Synthesis of N-(4-aminophenyl)-4-chlorobenzenesulfonamide:

[0133] The method and conditions for synthesis are the same as in Example 1(3), except that 4-chlorobenzenesulfonyl chloride is used as the raw material;

[0134] (4) Synthesis of N-(4-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0135] Synthesized as in the method and conditions of Example 1(4), except that N-(4- aminophenyl)-4-chlorobenzenesulfonamide was used as the starting material;

[0136] Example 6: Synthesis of N-(4-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I6):

[0137] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0138] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0139] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0140] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0141] (3) Synthesis of N-(4-aminophenyl)-4-chlorobenzenesulfonamide:

[0142] Synthesized as in the method and conditions of Example 1(3), except that 4-chlorobenzenesulfonyl chloride was used as the starting material;

[0143] (4) Synthesis of N-(4-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0144] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(4-aminophenyl)-4- chlorobenzenesulfonamide were used as the starting materials;

[0145] Example 7: Synthesis of N-(4-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I7):

[0146] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0147] Synthesized as in the method and conditions of Example 1(1);

[0148] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0149] Synthesized as in the method and conditions of Example 1(2) except that 2- chloro-5-trifluoromethylacetophenone was used as the starting material;

[0150] (3) Synthesis of N-(4-aminophenyl)-2-fluorobenzenesulfonamide:

[0151] Synthesized as in the method and conditions of Example 1(3) except that 2- fluorobenzenesulfonyl chloride was used as the starting material;

[0152] (4) Synthesis of N-(4-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0153] Synthesized as in the method and conditions of Example 1(4) except that N-(4- aminophenyl)-2-fluorobenzenesulfonamide was used as the starting material;

[0154] Example 8: Synthesis of N-(4-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I8):

[0155] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0156] Synthesized as in the method and conditions of Example 1(1) except that 2-chloro- 5-trifluoromethylacetophenone was used as the starting material;

[0157] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0158] Synthesized as in the method and conditions of Example 1(2) except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0159] (3) Synthesis of N-(4-aminophenyl)-2-fluorobenzenesulfonamide:

[0160] Synthesized as in the method and conditions of Example 1(3) except that 2- fluorobenzenesulfonyl chloride was used as the starting material;

[0161] (4) Synthesis of N-(4-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0162] Synthesized as in the method and conditions of Example 1(4) except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(4-aminophenyl)-2- fluorobenzenesulfonamide were used as the starting materials;

[0163] Example 9: Synthesis of N-(4-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I9):

[0164] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0165] Synthesized as in Example 1(1) method and conditions;

[0166] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0167] Synthesized as in Example 1(2) method and conditions;

[0168] (3) Synthesis of N-(4-aminophenyl)-2-chlorobenzenesulfonamide:

[0169] Synthesized as in Example 1(3) method and conditions, except that 2-chlorobenzenesulfonyl chloride was used as a starting material;

[0170] (4) Synthesis of N-(4-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0171] Synthesized as in Example 1(4) method and conditions, except that N-(4- aminophenyl)-2-chlorobenzenesulfonamide was used as a starting material;

[0172] Example 10: N-(4-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (110):

[0173] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2- carboxylate:

[0174] Synthesized as in Example 1(1) method and conditions, except that 2-chloro-5- trifluoromethylacetophenone was used as a starting material;

[0175] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0176] Synthesized as in Example 1(2) method and conditions, except that ethyl 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylate was used as a starting material;

[0177] (3) Synthesis of N-(4-aminophenyl)-2-chlorobenzenesulfonamide:

[0178] Synthesized as in Example 1(3) method and conditions, except that 2-chlorobenzenesulfonyl chloride was used as a starting material;

[0179] (4) Synthesis of N-(4-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0180] Synthesized as in the method and conditions of Example 1 (4) except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(4-aminophenyl)-2- chlorobenzenesulfonamide were used as starting materials;

[0181] Example 11: Synthesis of N-(4-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I11):

[0182] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0183] Synthesized as in the method and conditions of Example 1 (1) except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0184] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0185] Synthesized as in the method and conditions of Example 1 (2) except that ethyl 5- trifluoromethylbenzo[b]thiophene-2-carboxylate was used as starting material;

[0186] (3) Synthesis of N-(4-aminophenyl)-3-fluorobenzenesulfonamide:

[0187] Synthesized as in the method and conditions of Example 1 (3) except that 3-fluorobenzenesulfonyl chloride was used as starting material;

[0188] (4) Synthesis of N-(4-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0189] Synthesized as in the method and conditions of Example 1 (4) except that N-(4- aminophenyl)-3-fluorobenzenesulfonamide was used as starting material;

[0190] Example 12: Synthesis of N-(4-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I12):

[0191] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0192] Synthesized as in the method and conditions of Example 1 (1) except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0193] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0194] Synthesized as in the method and conditions of Example 1 (2) except that ethyl 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylate was used as starting material;

[0195] (3) Synthesis of N-(4-aminophenyl)-3-fluorobenzenesulfonamide:

[0196] Synthesized as in the method and conditions of Example 1(3), except that 3- chlorobenzenesulfonyl chloride was used as the starting material;

[0197] (4) Synthesis of N-(4-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0198] Synthesized as in the method and conditions of Example 1(4), except that N-(4- aminophenyl)-3-chlorobenzenesulfonamide and 5-trifluoromethylbenzo[b]thiophene-2- carboxylic acid were used as the starting materials;

[0199] Example 13: Synthesis of N-(4-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I13):

[0200] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0201] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0202] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0203] Synthesized as in the method and conditions of Example 1(2);

[0204] (3) Synthesis of N-(4-aminophenyl)-3-chlorobenzenesulfonamide:

[0205] Synthesized as in the method and conditions of Example 1(3), except that 3- chlorobenzenesulfonyl chloride was used as the starting material;

[0206] (4) Synthesis of N-(4-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0207] Synthesized as in the method and conditions of Example 1(4), except that N-(4- aminophenyl)-3-chlorobenzenesulfonamide was used as the starting material;

[0208] Example 14: Synthesis of N-(4-((3-chlorophenyl)sulfonamido)phenyl)-3- methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (I14):

[0209] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2- carboxylate:

[0210] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0211] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0212] Synthesized as in Example 1 (2) with the exception that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0213] (3) Synthesis of N-(4-aminophenyl)-3-chlorobenzenesulfonamide:

[0214] Synthesized as in Example 1 (3) with the exception that 3-chlorobenzenesulfonyl chloride was used as the starting material;

[0215] (4) Synthesis of N-(4-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0216] Synthesized as in Example 1 (4) with the exception that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(4-aminophenyl)-3- chlorobenzenesulfonamide were used as the starting materials;

[0217] Example 15: Synthesis of N-(4-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I 15):

[0218] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0219] Synthesized as in Example 1 (1);

[0220] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0221] Synthesized as in Example 1 (2);

[0222] (3) Synthesis of N-(4-aminophenyl)-4-fluorobenzenesulfonamide:

[0223] Synthesized as in Example 1 (3) with the exception that 4-fluorobenzenesulfonyl chloride was used as the starting material;

[0224] (4) Synthesis of N-(4-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0225] Synthesized as in Example 1 (4) with the exception that N-(4-aminophenyl)-4- fluorobenzenesulfonamide was used as the starting material;

[0226] Example 16: Synthesis of N-(4-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I 16):

[0227] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0228] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0229] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0230] Synthesized as in the method and conditions of Example 1(2), except that ethyl 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylate was used as the starting material;

[0231] (3) Synthesis of N-(4-aminophenyl)-4-fluorobenzenesulfonamide:

[0232] Synthesized as in the method and conditions of Example 1(3), except that 4-fluorobenzenesulfonyl chloride was used as the starting material;

[0233] (4) Synthesis of N-(4-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0234] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(4-aminophenyl)-4- fluorobenzenesulfonamide were used as the starting materials;

[0235] Example 17: Synthesis of N-(4-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (I17):

[0236] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0237] Synthesized as in the method and conditions of Example 1(1);

[0238] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0239] Synthesized as in the method and conditions of Example 1(2);

[0240] (3) Synthesis of N-(4-aminophenyl)benzenesulfonamide:

[0241] Synthesized as in the method and conditions of Example 1(3), except that benzenesulfonyl chloride was used as the starting material;

[0242] (4) Synthesis of N-(4-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0243] Synthesized by the method and under the conditions of Example 1(4), except that N-(4- aminophenyl)-benzenesulfonamide was used as the starting material;

[0244] Example 18: Synthesis of N-(4-((phenyl)sulfonamidyl)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I 18):

[0245] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0246] Synthesized by the method and under the conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0247] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0248] Synthesized by the method and under the conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0249] (3) Synthesis of N-(4-aminophenyl)-benzenesulfonamide:

[0250] Synthesized by the method and under the conditions of Example 1(3), except that benzenesulfonyl chloride was used as the starting material;

[0251] (4) Synthesis of N-(4-((phenyl)sulfonamidyl)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0252] Synthesized by the method and under the conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(4-aminophenyl)-benzenesulfonamide were used as the starting materials;

[0253] Example 19: Synthesis of N-(3-((4-methylphenyl)sulfonamidyl)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I 19):

[0254] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0255] Synthesized by the method and under the conditions of Example 1(1);

[0256] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0257] Synthesized by the method and under the conditions of Example 1(2);

[0258] (3) Synthesis of N-(3-aminophenyl)-4-methylbenzenesulfonamide:

[0259] Synthesized according to the method and conditions of Example 1(3), except that m- phenylenediamine was used as the starting material;

[0260] (4) Synthesis of N-(3-((4-methylphenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0261] Synthesized according to the method and conditions of Example 1(4), except that N-(3- aminophenyl)-4-methylbenzenesulfonamide was used as the starting material;

[0262] Example 20: Synthesis of N-(3-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I20):

[0263] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0264] Synthesized according to the method and conditions of Example 1(1), except that 2-chloro- 5-trifluoromethylacetophenone was used as the starting material;

[0265] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0266] Synthesized according to the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0267] (3) Synthesis of N-(3-aminophenyl)-4-methylbenzenesulfonamide:

[0268] Synthesized according to the method and conditions of Example 1(3), except that m- phenylenediamine was used as the starting material;

[0269] (4) Synthesis of N-(3-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0270] Synthesized according to the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-4- methylbenzenesulfonamide were used as the starting materials;

[0271] Example 21: Synthesis of N-(3-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (I21):

[0272] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0273] Synthesized according to the method and conditions of Example 1(1);

[0274] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0275] Synthesized according to the method and conditions of Example 1(2);

[0276] (3) Synthesis of N-(3-aminophenyl)-benzenesulfonamide:

[0277] Synthesized according to the method and conditions of Example 1(3), except that m- phenylenediamine and benzenesulfonyl chloride were used as starting materials;

[0278] (4) Synthesis of N-(3-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2- carboxamide:

[0279] Synthesized according to the method and conditions of Example 1(4), except that N-(3- aminophenyl)-benzenesulfonamide was used as starting material;

[0280] Example 22: Synthesis of N-(3-((phenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I22):

[0281] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0282] Synthesized according to the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0283] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0284] Synthesized according to the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as starting material;

[0285] (3) Synthesis of N-(3-aminophenyl)-benzenesulfonamide:

[0286] Synthesized according to the method and conditions of Example 1(3), except that m- phenylenediamine and benzenesulfonyl chloride were used as starting materials;

[0287] (4) Synthesis of N-(3-((phenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2- carboxamide:

[0288] Synthesized according to the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-benzenesulfonamide were used as starting materials;

[0289] Example 23: Synthesis of N-(3-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I23), comprising the following steps:

[0290] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0291] Synthesized as in Example 1(1) method and condition;

[0292] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0293] Synthesized as in Example 1(2) method and condition;

[0294] (3) Synthesis of N-(3-aminophenyl)-4-fluorobenzenesulfonamide:

[0295] Synthesized as in Example 1(3) method and condition, except that m-phenylenediamine and 4-fluorobenzenesulfonyl chloride were used as starting materials;

[0296] (4) Synthesis of N-(3-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0297] Synthesized as in Example 1(4) method and condition, except that N-(3- aminophenyl)-4-fluorobenzenesulfonamide was used as starting material;

[0298] Example 24: Synthesis of N-(3-((4-fluorophenyl)sulfonamido)phenyl)-3- methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (I24):

[0299] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0300] Synthesized as in Example 1(1) method and condition, except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0301] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0302] Synthesized as in Example 1(2) method and condition, except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as starting material;

[0303] (3) Synthesis of N-(3-aminophenyl)-4-fluorobenzenesulfonamide:

[0304] Synthesized as in Example 1(3) method and condition, except that m-phenylenediamine and 4-fluorobenzenesulfonyl chloride were used as starting materials;

[0305] (4) Synthesis of N-(3-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0306] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-4- fluorobenzenesulfonamide were used as starting materials;

[0307] Example 25: Synthesis of N-(3-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I25):

[0308] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0309] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0310] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0311] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid was used as starting material;

[0312] (3) Synthesis of N-(3-aminophenyl)-4-chlorobenzenesulfonamide:

[0313] Synthesized as in the method and conditions of Example 1(3), except that m-phenylenediamine and 4-chlorobenzenesulfonyl chloride were used as starting materials;

[0314] (4) Synthesis of N-(3-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0315] Synthesized as in the method and conditions of Example 1(4), except that N-(3- aminophenyl)-4-chlorobenzenesulfonamide was used as starting material;

[0316] Example 26: Synthesis of N-(3-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I26):

[0317] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0318] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0319] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0320] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0321] (3) Synthesis of N-(3-amino phenyl)-4-chlorobenzenesulfonamide:

[0322] Synthesized as in the method and conditions of Example 1(3), except that m-phenylenediamine and 4-chlorobenzenesulfonyl chloride were used as the starting materials;

[0323] (4) Synthesis of N-(3-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0324] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-amino phenyl)-4- chlorobenzenesulfonamide were used as the starting materials;

[0325] Example 27: Synthesis of N-(3-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I27):

[0326] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0327] Synthesized as in the method and conditions of Example 1(1);

[0328] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0329] Synthesized as in the method and conditions of Example 1(2);

[0330] (3) Synthesis of N-(3-amino phenyl)-3-fluorobenzenesulfonamide:

[0331] Synthesized as in the method and conditions of Example 1(3), except that m-phenylenediamine and 3-fluorobenzenesulfonyl chloride were used as the starting materials;

[0332] (4) Synthesis of N-(3-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0333] Synthesized as in the method and conditions of Example 1(4), except that N-(3-amino phenyl)-3-fluorobenzenesulfonamide was used as the starting material;

[0334] Example 28: Synthesis of N-(3-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I28):

[0335] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0336] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0337] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0338] Synthesized as in the method and conditions of Example 1(2), except that ethyl 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylate was used as the starting material;

[0339] (3) Synthesis of N-(3-aminophenyl)-3-fluorobenzenesulfonamide:

[0340] Synthesized as in the method and conditions of Example 1(3), except that m-phenylenediamine and 3-fluorobenzenesulfonyl chloride were used as the starting materials;

[0341] (4) Synthesis of N-(3-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0342] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-3- fluorobenzenesulfonamide were used as the starting materials;

[0343] Example 29: Synthesis of N-(3-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I29):

[0344] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0345] Synthesized as in the method and conditions of Example 1(1);

[0346] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0347] Synthesized as in the method and conditions of Example 1(2);

[0348] (3) Synthesis of N-(3-aminophenyl)-2-fluorobenzenesulfonamide:

[0349] Synthesized as in the method and conditions of Example 1(3), except that m-phenylenediamine and 2-fluorobenzenesulfonyl chloride were used as the starting materials;

[0350] (4) Synthesis of N-(3-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0351] Synthesized as in the method and conditions of Example 1(4), except that N-(3- aminophenyl)-2-fluorobenzenesulfonamide was used as the starting material;

[0352] Example 30: Synthesis of N-(3-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I30):

[0353] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0354] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0355] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0356] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0357] (3) Synthesis of N-(3-aminophenyl)-2-fluorobenzenesulfonamide:

[0358] Synthesized as in the method and conditions of Example 1(3), except that m-phenylenediamine and 2-fluorobenzenesulfonyl chloride were used as the starting materials;

[0359] (4) Synthesis of N-(3-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0360] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-2- fluorobenzenesulfonamide were used as the starting materials;

[0361] Example 31: Synthesis of N-(3-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I31):

[0362] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0363] Synthesized as in the method and conditions of Example 1(1);

[0364] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0365] Synthesized as in the method and conditions of Example 1(2);

[0366] (3) Synthesis of N-(3-aminophenyl)-3-chlorobenzenesulfonamide:

[0367] Synthesized as in the method and conditions of Example 1(3), except that m- phenylenediamine and 3-chlorobenzenesulfonyl chloride were used as starting materials;

[0368] (4) Synthesis of N-(3-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0369] Synthesized as in the method and conditions of Example 1(4), except that N-(3- aminophenyl)-3-chlorobenzenesulfonamide was used as starting material;

[0370] Example 32: Synthesis of N-(3-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I32):

[0371] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0372] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0373] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0374] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as starting material;

[0375] (3) Synthesis of N-(3-aminophenyl)-3-chlorobenzenesulfonamide:

[0376] Synthesized as in the method and conditions of Example 1(3), except that m- phenylenediamine and 3-chlorobenzenesulfonyl chloride were used as starting materials;

[0377] (4) Synthesis of N-(3-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0378] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-3- chlorobenzenesulfonamide were used as starting materials;

[0379] Example 33: Synthesis of N-(3-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I33):

[0380] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0381] As in Example 1(1), the method and conditions for synthesis;

[0382] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0383] As in Example 1(2), the method and conditions for synthesis;

[0384] (3) Synthesis of N-(3-aminophenyl)-2-chlorobenzenesulfonamide:

[0385] The method and conditions for synthesis are the same as in Example 1(3), except that m-phenylenediamine and 2-chlorobenzenesulfonyl chloride are used as raw materials;

[0386] (4) Synthesis of N-(3-((2-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0387] The synthesis is performed as described in Example 1(4), except that N-(3-aminophenyl)-2-chlorobenzenesulfonamide is used as the raw material.

[0388] Example 34: Synthesis of N-(3-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (Ⅰ34):

[0389] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0390] The synthesis is performed as described in Example 1(1), except that 2-chloro-5-trifluoromethylacetophenone is used as the raw material.

[0391] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0392] The synthesis was performed as described in Example 1(2) using the same method and conditions, except that ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate was used as the raw material.

[0393] (3) Synthesis of N-(3-aminophenyl)-2-chlorobenzenesulfonamide:

[0394] The method and conditions for synthesis are the same as in Example 1(3), except that m-phenylenediamine and 2-chlorobenzenesulfonyl chloride are used as raw materials;

[0395] (4) Synthesis of N-(3-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0396] The synthesis was performed as described in Example 1(4), except that 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-2-chlorobenzenesulfonamide were used as raw materials.

[0397] Example 35: Synthesis of N-(3-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I35):

[0398] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0399] Synthesized according to the method and conditions of Example 1(1);

[0400] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0401] Synthesized according to the method and conditions of Example 1(2);

[0402] (3) Synthesis of N-(3-aminophenyl)-2-bromobenzenesulfonamide:

[0403] Synthesized according to the method and conditions of Example 1(3), except that m- phenylenediamine and 2-bromobenzenesulfonyl chloride were used as starting materials;

[0404] (4) Synthesis of N-(3-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0405] Synthesized according to the method and conditions of Example 1(4), except that N-(3- aminophenyl)-2-bromobenzenesulfonamide was used as a starting material;

[0406] Example 36: Synthesis of N-(3-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I36):

[0407] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0408] Synthesized according to the method and conditions of Example 1(1), except that 2- chloro-5-trifluoromethylacetophenone was used as a starting material;

[0409] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0410] Synthesized according to the method and conditions of Example 1(2), except that ethyl 3- methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate was used as a starting material;

[0411] (3) Synthesis of N-(3-aminophenyl)-2-bromobenzenesulfonamide:

[0412] Synthesized according to the method and conditions of Example 1(3), except that m- phenylenediamine and 2-bromobenzenesulfonyl chloride were used as starting materials;

[0413] (4) Synthesis of N-(3-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0414] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-2- bromobenzenesulfonamide were used as starting materials;

[0415] Example 37: Synthesis of N-(2-((4-methylphenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I37):

[0416] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0417] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0418] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0419] Synthesized as in the method and conditions of Example 1(2);

[0420] (3) Synthesis of N-(2-aminophenyl)-4-methylbenzenesulfonamide:

[0421] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 4-methylbenzenesulfonyl chloride were used as starting materials;

[0422] (4) Synthesis of N-(2-((4-methylphenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0423] Synthesized as in the method and conditions of Example 1(4), except that N-(2- aminophenyl)-4-methylbenzenesulfonamide was used as starting material;

[0424] Example 38: Synthesis of N-(2-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I38):

[0425] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0426] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0427] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0428] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0429] (3) Synthesis of N-(2-aminophenyl)-4-methylbenzenesulfonamide:

[0430] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 4-methylbenzenesulfonyl chloride were used as the starting materials;

[0431] (4) Synthesis of N-(2-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0432] Synthesized as in the method and conditions of Example 1(4), except that N-(2- aminophenyl)-4-methylbenzenesulfonamide was used as the starting material;

[0433] Example 39: Synthesis of N-(2-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I39):

[0434] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0435] Synthesized as in the method and conditions of Example 1(1);

[0436] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0437] Synthesized as in the method and conditions of Example 1(2);

[0438] (3) Synthesis of N-(2-aminophenyl)-4-fluorobenzenesulfonamide:

[0439] Synthesized as in the method and conditions of Example 1(3), except that o- phenylenediamine and 4-fluorobenzenesulfonyl chloride were used as the starting materials;

[0440] (4) Synthesis of N-(2-((4-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0441] Synthesized as in the method and conditions of Example 1(4), except that N-(2- aminophenyl)-4-fluorobenzenesulfonamide was used as the starting material;

[0442] Example 40: Synthesis of N-(2-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I40):

[0443] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0444] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0445] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0446] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0447] (3) Synthesis of N-(2-aminophenyl)-4-fluorobenzenesulfonamide:

[0448] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 4-fluorobenzenesulfonyl chloride were used as the starting materials;

[0449] (4) Synthesis of N-(2-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0450] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(3-aminophenyl)-4- fluorobenzenesulfonamide were used as the starting materials;

[0451] Example 41: Synthesis of N-(2-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I41):

[0452] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0453] Synthesized as in the method and conditions of Example 1(1);

[0454] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0455] Synthesized as in the method and conditions of Example 1(2);

[0456] (3) Synthesis of N-(2-aminophenyl)-3-fluorobenzenesulfonamide:

[0457] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 3-fluorobenzenesulfonyl chloride were used as the starting materials;

[0458] (4) Synthesis of N-(2-((3-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0459] Synthesized by the method and in the conditions of Example 1(4), except that N-(2- aminophenyl)-3-fluorobenzenesulfonamide was used as the starting material;

[0460] Example 42: Synthesis of N-(2-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I42):

[0461] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0462] Synthesized by the method and in the conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0463] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0464] Synthesized by the method and in the conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0465] (3) Synthesis of N-(2-aminophenyl)-3-fluorobenzenesulfonamide:

[0466] Synthesized by the method and in the conditions of Example 1(3), except that o-phenylenediamine and 3-fluorobenzenesulfonyl chloride were used as the starting materials;

[0467] (4) Synthesis of N-(2-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0468] Synthesized by the method and in the conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(2-aminophenyl)-3- fluorobenzenesulfonamide were used as the starting materials;

[0469] Example 43: Synthesis of N-(2-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (I43):

[0470] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0471] Synthesized by the method and in the conditions of Example 1(1);

[0472] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0473] Synthesized by the method and in the conditions of Example 1(2);

[0474] (3) Synthesis of N-(2-aminophenyl)-benzenesulfonamide:

[0475] Synthesized as in the method and conditions of Example 1(3), except that o- phenylenediamine and benzenesulfonyl chloride were used as starting materials;

[0476] (4) Synthesis of N-(2-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0477] Synthesized as in the method and conditions of Example 1(4), except that N-(2- aminophenyl)-benzenesulfonamide was used as starting material;

[0478] Example 44: Synthesis of N-(2-((phenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I44):

[0479] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0480] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0481] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0482] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as starting material;

[0483] (3) Synthesis of N-(2-aminophenyl)-benzenesulfonamide:

[0484] Synthesized as in the method and conditions of Example 1(3), except that o- phenylenediamine and benzenesulfonyl chloride were used as starting materials;

[0485] (4) Synthesis of N-(2-((phenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0486] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(2-aminophenyl)- benzenesulfonamide were used as starting materials;

[0487] Example 45: Synthesis of N-(2-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I45):

[0488] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0489] Synthesized as in the method and conditions of Example 1(1);

[0490] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0491] Synthesized as in Example 1 (2) with the exception that 2-chloro-5- trifluoromethylacetophenone was used as the starting material.

[0492] (3) Synthesis of N-(2-aminophenyl)-2-fluorobenzenesulfonamide:

[0493] Synthesized as in Example 1 (3) with the exception that o-phenylenediamine and 2-fluorobenzenesulfonyl chloride were used as the starting materials.

[0494] (4) Synthesis of N-(2-((2-fluorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0495] Synthesized as in Example 1 (4) with the exception that N-(2- aminophenyl)-2-fluorobenzenesulfonamide was used as the starting material.

[0496] Example 46: Synthesis of N-(2-((2-fluorophenyl)sulfonamido)phenyl)-3- methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (I46):

[0497] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0498] Synthesized as in Example 1 (1) with the exception that 2-chloro-5- trifluoromethylacetophenone was used as the starting material.

[0499] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0500] Synthesized as in Example 1 (2) with the exception that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material.

[0501] (3) Synthesis of N-(2-aminophenyl)-2-fluorobenzenesulfonamide:

[0502] Synthesized as in Example 1 (3) with the exception that o-phenylenediamine and 2-fluorobenzenesulfonyl chloride were used as the starting materials.

[0503] (4) Synthesis of N-(2-((2-fluorophenyl)sulfonamido)phenyl)-3- methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0504] Synthesized as in Example 1 (4) with the exception that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(2- aminophenyl)-2-fluorobenzenesulfonamide were used as the starting materials.

[0505] Example 47: Synthesis of N-(2-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I47):

[0506] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0507] Synthesized as in Example 1(1) method and condition;

[0508] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0509] Synthesized as in Example 1(2) method and condition;

[0510] (3) Synthesis of N-(2-aminophenyl)-3-chlorobenzenesulfonamide:

[0511] Synthesized as in Example 1(3) method and condition, except that o-phenylenediamine and 3-chlorobenzenesulfonyl chloride were used as starting materials;

[0512] (4) Synthesis of N-(2-((3-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0513] Synthesized as in Example 1(4) method and condition, except that N-(2- aminophenyl)-3-chlorobenzenesulfonamide was used as starting material;

[0514] Example 48: Synthesis of N-(2-((3-chlorophenyl)sulfonamido)phenyl)-3- methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (I48):

[0515] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0516] Synthesized as in Example 1(1) method and condition, except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0517] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0518] Synthesized as in Example 1(2) method and condition, except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as starting material;

[0519] (3) Synthesis of N-(2-aminophenyl)-3-chlorobenzenesulfonamide:

[0520] Synthesized as in Example 1(3) method and condition, except that o-phenylenediamine and 3-chlorobenzenesulfonyl chloride were used as starting materials;

[0521] (4) Synthesis of N-(2-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0522] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(2-aminophenyl)-3-chlorobenzenesulfonamide were used as starting materials;

[0523] Example 49: Synthesis of N-(2-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I49):

[0524] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0525] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0526] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0527] Synthesized as in the method and conditions of Example 1(2), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0528] (3) Synthesis of N-(2-aminophenyl)-2-chlorobenzenesulfonamide:

[0529] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 2-chlorobenzenesulfonyl chloride were used as starting materials;

[0530] (4) Synthesis of N-(2-((2-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0531] Synthesized as in the method and conditions of Example 1(4), except that N-(2- aminophenyl)-2-chlorobenzenesulfonamide was used as starting material;

[0532] Example 50: Synthesis of N-(2-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I50):

[0533] (1) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0534] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as starting material;

[0535] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0536] Synthesized as in the method and conditions of Example 1(2), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester was used as the starting material;

[0537] (3) Synthesis of N-(2-aminophenyl)-2-chlorobenzenesulfonamide:

[0538] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 2-chlorobenzenesulfonyl chloride were used as the starting materials;

[0539] (4) Synthesis of N-(2-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0540] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(2-aminophenyl)-2- chlorobenzenesulfonamide were used as the starting materials;

[0541] Example 51: Synthesis of N-(2-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I51):

[0542] (1) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid ethyl ester:

[0543] Synthesized as in the method and conditions of Example 1(1);

[0544] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0545] Synthesized as in the method and conditions of Example 1(2);

[0546] (3) Synthesis of N-(2-aminophenyl)-4-chlorobenzenesulfonamide:

[0547] Synthesized as in the method and conditions of Example 1(3), except that o- phenylenediamine and 4-chlorobenzenesulfonyl chloride were used as the starting materials;

[0548] (4) Synthesis of N-(2-((4-chlorophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0549] Synthesized as in the method and conditions of Example 1(4), except that N-(2- aminophenyl)-4-chlorobenzenesulfonamide was used as the starting material;

[0550] Example 52: Synthesis of N-(2-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I52):

[0551] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0552] Synthesized as in the method and conditions of Example 1(1), except that 2-chloro-5- trifluoromethylacetophenone was used as the starting material;

[0553] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0554] Synthesized as in the method and conditions of Example 1(2), except that ethyl 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylate was used as the starting material;

[0555] (3) Synthesis of N-(2-aminophenyl)-4-chlorobenzenesulfonamide:

[0556] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 4-chlorobenzenesulfonyl chloride were used as the starting materials;

[0557] (4) Synthesis of N-(2-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0558] Synthesized as in the method and conditions of Example 1(4), except that 3-methyl-5- trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(2-aminophenyl)-4- chlorobenzenesulfonamide were used as the starting materials;

[0559] Example 53: Synthesis of N-(2-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide (I53):

[0560] (1) Synthesis of ethyl 5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0561] Synthesized as in the method and conditions of Example 1(1);

[0562] (2) Synthesis of 5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0563] Synthesized as in the method and conditions of Example 1(2);

[0564] (3) Synthesis of N-(2-aminophenyl)-2-bromobenzenesulfonamide:

[0565] Synthesized as in the method and conditions of Example 1(3), except that o-phenylenediamine and 2-bromobenzenesulfonyl chloride were used as the starting materials;

[0566] (4) Synthesis of N-(2-((2-bromophenyl)sulfonamido)phenyl)-5- (trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0567] The synthesis is performed as described in Example 1(4), except that N-(2-aminophenyl)-2-bromobenzenesulfonamide is used as the raw material.

[0568] Example 54: Synthesis of N-(2-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide (Ⅰ54):

[0569] (1) Synthesis of ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate:

[0570] The synthesis is performed as described in Example 1(1), except that 2-chloro-5-trifluoromethylacetophenone is used as the raw material.

[0571] (2) Synthesis of 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid:

[0572] The synthesis was performed as described in Example 1(2), except that ethyl 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylate was used as the raw material.

[0573] (3) Synthesis of N-(2-aminophenyl)-2-bromobenzenesulfonamide:

[0574] The synthesis is performed as described in Example 1(3) using the same method and conditions, except that o-phenylenediamine and 2-bromobenzenesulfonyl chloride are used as raw materials;

[0575] (4) Synthesis of N-(2-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide:

[0576] The synthesis was performed as described in Example 1(4), except that 3-methyl-5-trifluoromethylbenzo[b]thiophene-2-carboxylic acid and N-(2-aminophenyl)-2-bromobenzenesulfonamide were used as raw materials.

[0577] The physicochemical properties of the benzo[b]thiophene derivatives containing sulfonamide units prepared in the above examples are shown in Tables 1, 2, and 3. Their structural formulas and proton nuclear magnetic resonance spectra (NMR spectra) are also described. 1 HNMR, carbon spectrum 13 The 12C NMR and high-resolution mass spectrometry (HRMS) data are shown in Table 4.

[0578] Table 1. Physicochemical properties of the target compounds in the examples.

[0579]

[0580]

[0581] Table 2 Physicochemical properties of the target compounds in the examples

[0582]

[0583] Table 3 Physico-chemical properties of example target compounds

[0584]

[0585]

[0586] Table 4 Structural formula and spectral data of example target compounds

[0587]

[0588]

[0589]

[0590]

[0591]

[0592]

[0593]

[0594]

[0595]

[0596]

[0597]

[0598]

[0599] Test Example 1, Antiviral activity of target compounds against Potato Y virus

[0600] (1) Test method

[0601] A. Virus purification

[0602] The method of Zhou Xueping (Zhou Xueping, Xu Zhixin, Xu Jing, Li Debao. Study on cucumber mosaic virus infecting luffa [J]. Journal of South China Agricultural University, 1995, 16(2): 74-79.) was used to select the upper leaves of Nicotiana tabacum. L plants infected by the virus for more than 3 weeks, which were homogenized in phosphate buffer, filtered through double-layer gauze, centrifuged at 8000g, treated with polyethylene glycol twice, and then centrifuged again. The precipitate was suspended in phosphate buffer to obtain the purified virus solution. The whole experiment was carried out at 4°C. The absorbance value at 260nm wavelength was measured by ultraviolet spectrophotometer, and the virus concentration was calculated according to the formula.

[0603] Virus concentration (mg / mL) = (A 260 × dilution factor) / E 0.1％ 1cm 260nm .

[0604] E represents the extinction coefficient, i.e. the light absorption value of a suspension with a concentration of 0.1% (1mg / mL) at a wavelength of 260nm and a light path of 1cm. The E of potato Y virus is 5.0. 0.1％ 1cm 260nm .

[0605] B. In vivo treatment of potato Y virus infection by the agent

[0606] In vivo treatment of infection by the agent: the Amaranthus palmeri plants at the 5-6 leaf stage with uniform growth were topped, and the whole leaves were inoculated with virus by evenly scattering gold sand and using a brush pen to dip the virus solution (6x10 -3 mg / mL). After natural drying, the leaves were washed with water. After the leaves dried, the left half of the leaves was lightly coated with the agent, and the right half of the leaves was coated with the corresponding solvent at the same concentration as the control. After 4-5 days, the number of withered spots was recorded, and the inhibition rate was calculated according to the following formula.

[0607] C. In vivo protection of potato Y virus infection by the agent

[0608] In vivo protection of potato Y virus infection by the agent: the Amaranthus palmeri plants at the 5-6 leaf stage with uniform growth were topped, and the left half of the leaves was lightly coated with the agent, and the right half of the leaves was coated with the corresponding solvent at the same concentration as the control. After 24 hours, the whole leaves were inoculated with virus by evenly scattering gold sand and using a brush pen to dip the virus solution (6x10 -3 mg / mL). The leaves were washed with water, and after 4-5 days, the number of withered spots was recorded, and the inhibition rate was calculated according to the following formula.

[0609] D. In vivo passivation of potato Y virus infection by the agent

[0610] In vivo inactivation of potato virus Y infection by the agent: Select amaranth plants with uniform growth at the 5-6 leaf stage, top them, sprinkle carborundum evenly over the entire leaf, and use a brush to apply virus solution (6×10). -3 Inoculate the left half of the leaf with the virus (mg / mL) and the right half with a mixture of the virus and the test compound after 30 min of reaction. After air drying, rinse the leaves with water. Record the number of necrotic spots after 4-5 days and calculate the inhibition rate using the following formula:

[0611]

[0612] The average number of necrotic spots on the untreated half-leaf and the average number of necrotic spots on the treated half-leaf were both calculated using the average of three replicates for each group.

[0613] Table 5. The therapeutic, protective, and inactivating activities of the target compounds against potato virus Y at a concentration of 500 μg / mL.

[0614]

[0615] Table 6. The therapeutic, protective, and inactivating activities of the target compounds against potato virus Y at a concentration of 500 μg / mL.

[0616]

[0617]

[0618] Table 7. The therapeutic, protective, and inactivating activities of the target compounds against potato virus Y at a concentration of 500 μg / mL.

[0619]

[0620] The anti-potato virus Y activity of benzo[b]thiophene derivatives containing sulfonamide units was tested using the half-leaf necrotic spot method at a concentration of 500 μg / mL, with ningnanmycin as the control agent. The bioassay results in Tables 5, 6, or 7 show that most target compounds exhibited some anti-potato virus Y activity. The compounds generally showed better therapeutic and protective activities than the control agent ningnanmycin. Specifically, compound I1 (67.88%, 67.44%) showed significantly higher therapeutic and protective activities than the control agent ningnanmycin (47.20%, 46.62%); the inactivation activities of compounds I5, I38, and I41 (78.09%, 85.06%, and 80.40%) were comparable to those of the control agent ningnanmycin (84.20%).

[0621] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A benzo[b]thiophene compound containing a sulfonamide unit or a salt thereof, characterized in that... It has the characteristics shown in general formula (I): In the formula: R 1 Independently selected from trifluoromethyl; R 2 Independently selected from hydrogen, deuterium, halogen, and unsubstituted C1-C6 alkyl groups; R 3 Independently selected from substituted or unsubstituted phenyl groups; The substitution refers to the optional substitution by one or more of halogens, C1-C6 alkyl groups.

2. The benzo[b]thiophene compound or its salt containing a sulfonamide unit according to claim 1, characterized in that: R 1 Independently selected from trifluoromethyl; R 2 Independently selected from hydrogen, deuterium, halogens, and methyl groups; R 3 Independently selected from phenyl, .

3. The benzo[b]thiophene compound or its salt containing a sulfonamide unit according to claim 1, characterized in that... Selected from the following specific compounds: Compound I1: N-(4-((4-methylphenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I2: N-(4-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I3: N-(4-((2-bromophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I4: N-(4-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I5: N-(4-((4-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I6: N-(4-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I7: N-(4-((2-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I8: N-(4-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I9: N-(4-((2-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I10: N-(4-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I11: N-(4-((3-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I12: N-(4-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I13: N-(4-((3-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I14: N-(4-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I15: N-(4-((4-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I16: N-(4-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I17: N-(4-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I18: N-(4-((phenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I19: N-(3-((4-methylphenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I20: N-(3-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I21: N-(3-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I22: N-(3-((phenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I23: N-(3-((4-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I24: N-(3-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I25: N-(3-((4-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I26: N-(3-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I27: N-(3-((3-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I28: N-(3-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I29: N-(3-((2-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I30: N-(3-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I31: N-(3-((3-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I32: N-(3-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I33: N-(3-((2-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I34: N-(3-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I35: N-(3-((2-bromophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I36: N-(3-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I37: N-(2-((4-methylphenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I38: N-(2-((4-methylphenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I39: N-(2-((4-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I40: N-(2-((4-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I41: N-(2-((3-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I42: N-(2-((3-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I43: N-(2-((phenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I44: N-(2-((phenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I45: N-(2-((2-fluorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I46: N-(2-((2-fluorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I47: N-(2-((3-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I48: N-(2-((3-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I49: N-(2-((2-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I50: N-(2-((2-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I51: N-(2-((4-chlorophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I52: N-(2-((4-chlorophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I53: N-(2-((2-bromophenyl)sulfonamido)phenyl)-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide; Compound I54: N-(2-((2-bromophenyl)sulfonamido)phenyl)-3-methyl-5-(trifluoromethyl)benzo[b]thiophene-2-carboxamide.

4. The method for preparing the benzo[b]thiophene compound or its salt containing a sulfonamide unit as described in claim 1, characterized in that... include:

5. The method for preparing the benzo[b]thiophene compound or its salt containing a sulfonamide unit as described in claim 4, characterized in that... include:

6. A composition, characterized in that... The composition contains any of the compounds or salts thereof as described in claims 1-3, and agriculturally available adjuvants or fungicides, insecticides or herbicides; the formulation of the composition is selected from emulsifiable concentrates (EC), powders (DP), wettable powders (WP), granules (GR), aqueous solutions (AS), suspensions (SC), ultra-low volume sprays (ULV), soluble powders (SP), microcapsules (MC), fumigants (FU), water-in-oil emulsions (EW), and water-dispersible granules (WG).

7. Use of the compound or salt thereof of any one of claims 1-3, or the composition of claim 6, in the prevention and control of agricultural pests and diseases, wherein the agricultural pest or disease is potato virus Y.

8. A method for preventing and controlling agricultural pests and diseases, characterized in that: To subject the compound or salt thereof of any one of claims 1-3, or the composition of claim 6, to a hazardous substance or its living environment; The agricultural pest and disease mentioned is potato virus Y disease.

9. A method for protecting plants from agricultural pests and diseases, comprising the step of contacting a pest with a compound or salt thereof as described in any one of claims 1-3, or a composition as described in claim 6; wherein the agricultural pest or disease is potato virus Y.

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