Indothiazole derivatives, their synthesis methods and applications

Abstract

This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to indomethacin derivatives, their synthesis methods, and applications. The derivatives possess the chemical structures described in formulas (I), (II), and (III). This invention is the first to propose a series of novel indomethacin derivatives. Furthermore, this invention also proposes a synthesis method for indomethacin derivatives, using 5-hydroxy-1-indanone as a base material, to obtain the indomethacin derivatives of this invention through a series of reactions. This synthesis method yields high-yield products that are easily separated, making it the optimal method for preparing the indomethacin derivatives of this invention. Bioassays have confirmed that the indomethacin derivatives provided by this invention exhibit good toxic activity against aphids, spider mites, and armyworms, and can be applied to the control of plant pests.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to indothiazole derivatives and their synthesis methods and applications. Background Technology

[0002] Piercing-sucking and chewing pests, such as aphids, spider mites, and armyworms, are among the major pests affecting most crops in agriculture. However, due to the long-term and frequent use of pesticides, they have developed particularly serious resistance. Therefore, there is an urgent need to develop new and better insecticides.

[0003] Indanones are a class of organic compounds with an indenyl ring skeleton and a ketone carbonyl group on the ring. They are the core structural unit of many natural products and synthetic drugs. Their basic structure consists of a benzene ring coupled to a five-membered carbon ring with a carbonyl group (C=O), forming a rigid, planar fused ring system. Their basic structures mainly include 1-indanone, 2-indanone, as well as 1,2-indanedione, 1,3-indanedione, and ninhydrine, among others. Indanone structures are widely found in many natural products with significant biological activity. For example, many indanone compounds isolated from plants such as algae, mosses, vines, or microorganisms like Streptomyces have excellent inhibitory activity against the growth of human vascular endothelial factor and are used to regulate tumor angiogenesis. In addition, indanone structures are also found in synthetic drugs, pesticides, dyes, amino acid colorimetric reagents, and various fine chemicals. Indanones have distinctive structural features, especially 1-indanone. Due to its unique electron distribution and ring strain, it can serve as a substrate for reactions, and its carbonyl ortho position is also prone to enolization, thus possessing rich chemical reactivity and providing a basis for structural derivatization.

[0004] Thiazole compounds are a class of five-membered aromatic heterocyclic compounds containing nitrogen and sulfur atoms. Their unique electronic structure and molecular properties make them a "preferred backbone" in pesticide molecule design. The thiazole ring readily interacts with various targets in organisms through hydrogen bonds, van der Waals forces, and metal ion coordination, thus exhibiting a wide range of biological activities. Since Merck successfully developed the first thiazole fungicide, thiabendazole, in 1962, these compounds have rapidly become a research hotspot in the field of green pesticide creation due to their outstanding advantages, including low toxicity to humans and warm-blooded animals, high bioactivity, environmental friendliness, and easy degradation in the environment. Over the past sixty years, domestic and international pesticide research institutions have successfully developed dozens of commercialized thiazole pesticide varieties, covering multiple fields such as insecticides, fungicides, and herbicides. In terms of insecticides, there are neonicotinoids such as imidacloprid, thiamethoxam, thiamethoxam, and thiamethoxam, as well as thiazophos and flufenoxuron; in terms of fungicides, there are thifluzamide, thiazoxamide, bensulfuron-methyl, and seed dressing agents; in terms of herbicides, there are also safeners based on the thiazole structure and herbicides such as thiamethoxam.

[0005] This invention is based on the rational drug design concept of "active structural unit splicing," aiming to innovatively fuse the promising natural indanone skeleton with a highly efficient and mature thiazole pharmacophore. We hypothesize that the organic combination of the two can not only retain their original active characteristics, but also potentially generate novel mechanisms of action and biological activities that transcend single structures through structural complementarity and synergistic effects. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of the prior art and provide indothiazole derivatives, their synthesis methods, and applications.

[0007] The objective of this invention is achieved through the following technical solution:

[0008] The primary objective of this invention is to provide a series of novel indanthiazole derivatives having the chemical structures described in formula (I), (II), or (III):

[0009]

[0010] Wherein, R is any one of alkyl, phenyl, substituted phenyl or heterocyclic, and the alkyl is an aliphatic chain or cycloalkanes.

[0011] As a preferred embodiment, the chemical structural formula of the derivative is any one of 1 to 90:

[0012]

[0013]

[0014] In the formula, (2) to (8) represent the number of carbons at the position on the carbon chain of the derivative.

[0015] The second objective of this invention is to provide a method for synthesizing indenethiazole derivatives in high yield, the synthetic route being as follows:

[0016]

[0017] As a preferred embodiment, step a specifically involves: dissolving compound (A) in a mixed solvent of dichloromethane and ethyl acetate, adding copper bromide, and reacting at 70–80°C for 10–14 h to generate compound (B).

[0018] Step b is as follows: Compound (B) is dissolved in dichloromethane, tert-butyldimethylchlorosilane and imidazole are added, and the mixture is reacted at 0°C for 8 to 12 min and then at room temperature for 2 to 4 h to generate compound (C).

[0019] Step c specifically involves dissolving compound (C) in anhydrous ethanol, adding thiourea, and reacting at 85–95°C for 10–14 h to generate compound (D).

[0020] As a preferred embodiment, step d specifically involves dissolving compound (D) in anhydrous dichloromethane, adding triethylamine, 4-dimethylaminopyridine and acyl chloride sequentially, reacting at 0°C for 8–12 min, and then reacting at room temperature for 5–7 h to generate compound (E).

[0021] Step e specifically involves dissolving compound (D) in acetonitrile, then adding triethylamine, 4-dimethylaminopyridine, and sulfonyl chloride sequentially, reacting at 0°C for 10 min, and then reacting at room temperature for 5–7 h to generate compound (F).

[0022] Step f specifically involves dissolving compound (D) in acetone, adding potassium carbonate and benzyl bromide, and reacting at 70–80°C for 10–14 h to generate compound (G).

[0023] As a preferred embodiment, step g specifically involves dissolving compounds (E), (G), and (F) in tetrahydrofuran, adding tetrabutylammonium fluoride, and reacting at room temperature for 25–35 min to generate compounds (I), (II), or (III), respectively.

[0024] As a more preferred embodiment, the reaction reagents and conditions for each step in the synthetic route are as follows:

[0025] Step a: DCM, EtOAC, CuBr2, 75 ℃;

[0026] Step b: DCM, TBSCl, Imidazole, 0-25 ℃;

[0027] Step c: EtOH, Thiourea, 90 ℃;

[0028] Step d: DCM, Et3N, DMAP, RCOCl, 0-25 ℃;

[0029] Step e: MeCN, Et3N, DMAP, RSO2Cl, 0-25 ℃;

[0030] Step f: Acetone, K₂CO₃, RCH₂Br, 75 ℃;

[0031] Step g: THF, TBAF, 25 ℃.

[0032] A third objective of this invention is to provide the application of the above-mentioned indothiazole derivatives and the indothiazole derivatives synthesized by the above-mentioned method in the control of plant pests.

[0033] As a preferred embodiment, the plant pests are aphids, spider mites, and oriental armyworms.

[0034] A fourth objective of the present invention is to provide an insecticide comprising the above-mentioned indothiazole derivative.

[0035] To apply the indomethacin derivatives in agriculture and plant protection, those skilled in the art can use one or more of the indomethacin derivatives as insecticidal active ingredients, combined with pesticide-acceptable carriers or other agricultural active ingredients, to prepare easily applicable formulations, such as water-dispersible granules, wettable powders, or dispersible oil suspensions. The effective content of the indomethacin derivative in the insecticide ranges from 0.01% to 99.99%. When formulating the above-mentioned different formulations, those skilled in the art, in addition to using the selected fungicidal active ingredient, also need to select various adjuvants. Different pesticide formulation adjuvants can be selected as needed. These adjuvants can be one or more of the following: dispersion medium, dispersant, emulsifier, wetting agent, thickener, defoamer, antifreeze, disintegrant, binder, filler, etc.

[0036] The present invention has the following advantages:

[0037] (1) This invention proposes a series of novel indothiazole derivatives for the first time. In addition, this invention also proposes a method for synthesizing indothiazole derivatives. Using 5-hydroxy-1-indanone as a base material, the indothiazole derivatives of this invention are obtained through a series of reactions. The product prepared by this method has a high yield and the product is easy to separate, which is the optimal method for preparing the indothiazole derivatives of this invention.

[0038] (2) The indothiazole derivatives provided by the present invention have been confirmed by bioassay to have good toxic activity against aphids, spider mites and oriental armyworms, and can be applied to the control of plant pests. Detailed Implementation

[0039] The present invention will be further described below with reference to embodiments, but the scope of protection of the present invention is not limited to the following description:

[0040] Example 1: The specific method for synthesizing indothiazole derivatives is as follows:

[0041] (1) Weigh 5-hydroxy-1-indanone (1.94 g, 13.1 mmol) and copper bromide (7.32 g, 32.8 mmol) into a 200 mL dry round-bottom flask, and add a mixed solvent of dichloromethane (40 mL) and ethyl acetate (20 mL). The reaction mixture was stirred at 75 °C for 12 h. The reaction was monitored by TLC until the reaction was complete. The mixture was filtered first, then extracted three times with a mixture of water and dichloromethane. The combined organic layer was washed with brine. The organic phase was then dried on anhydrous Na2SO4 until no lumps were formed. The crude product compound (B) (2.92 g, 98.3%) was concentrated under reduced pressure. Compound (B) was a pale yellow oily liquid and could be used directly in the next step without purification.

[0042] (2) Compound (B) (2.27 g, 10 mmol), imidazole (2.04 g, 30 mmol), and tert-butyldimethylchlorosilane (3.01 g, 20 mmol) were weighed and added to a 200 mL dry round-bottom flask, and dichloromethane (40 mL) was added. The reaction mixture was stirred at 0 °C for 10 min and then cooled to room temperature for 3 h. The reaction was monitored by TLC until the reaction was complete. The mixture was extracted three times with a mixture of water and dichloromethane. The bound organic layer was washed with brine. The organic phase was collected and dried on anhydrous Na2SO4 until no agglomeration occurred. The crude product (C) was concentrated under reduced pressure. The crude product (C) was purified by silica gel column chromatography (petroleumether / ethyl acetate, 10:1, v / v) to obtain compound (C) (3.04 g, 89.2%).

[0043] (3) Weigh compound (C) (1.71 g, 5 mmol) and thiourea (0.49 g, 6.5 mmol) into a 100 mL dry round-bottom flask, and add anhydrous ethanol (30 mL). The reaction mixture was stirred at 90 °C for 12 h. The reaction was monitored by TLC until the reaction was complete. After concentration under reduced pressure, the mixture was extracted three times with a mixture of water and ethyl acetate. The bound organic layer was washed with brine. The organic phase was collected and dried on anhydrous Na2SO4 until no agglomeration occurred. The crude product (D) was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 2:1, v / v) to obtain compound (D) (1.07 g, 67.2%).

[0044] (4) Weigh compound (D) (0.15 g, 0.47 mmol), triethylamine (0.20 ml, 1.41 mmol), and 4-dimethylaminopyridine (0.03 g, 0.02 mmol) and add them to a 50 mL dry round-bottom flask. Add anhydrous dichloromethane (10 mL). Add acyl chloride (0.71 mmol) dropwise to the reaction mixture at 0 °C. Stir at 0 °C for 10 min and then react at room temperature for 6 h. Monitor the reaction by TLC until it is complete. Extract three times with a mixture of water and dichloromethane. Wash the combined organic layer with brine. Collect the organic phase and dry it on anhydrous Na2SO4 until no agglomeration occurs. Concentrate under reduced pressure to obtain crude product (E). Purify the crude product by silica gel column chromatography (petroleum ether / ethyl acetate, 5:1, v / v) to obtain a series of compounds (E) (65.8-92.5%).

[0045] (5) Weigh compound (D) (0.15 g, 0.47 mmol) and potassium carbonate (0.19 g, 1.41 mmol) into a 50 mL dry round-bottom flask, add acetone (10 mL), and then add benzyl bromide (0.94 mmol). The reaction mixture was reacted at 75 °C for 12 h. The reaction was monitored by TLC until the reaction was complete. After concentration under reduced pressure, the mixture was extracted three times with a mixture of water and ethyl acetate. The bound organic layer was washed with brine. The organic phase was collected and dried on anhydrous Na2SO4 until no agglomeration occurred. The crude product G was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate, 3:1, v / v) to obtain a series of compounds G (70.5-82.3%).

[0046] (6) Weigh compound (D) (0.15 g, 0.47 mmol), triethylamine (0.20 ml, 1.41 mmol), and 4-dimethylaminopyridine (0.03 g, 0.02 mmol) and add them to a 50 mL dry round-bottom flask. Add anhydrous dichloromethane (10 mL). Add sulfonyl chloride (0.71 mmol) dropwise to the reaction mixture at 0 °C. Stir at 0 °C for 10 min and then react at room temperature for 6 h. Monitor the reaction by TLC until it is complete. Extract three times with a mixture of water and dichloromethane. Wash the bound organic layer with brine. Collect the organic phase and dry it on anhydrous Na2SO4 until no agglomeration occurs. Concentrate under reduced pressure to obtain the crude product (F). Purify the crude product by silica gel column chromatography (petroleum ether / ethyl acetate, 4:1, v / v) to obtain a series of compounds (F) (60.8-90.1%).

[0047] (7) Weigh out compounds (E), (G), and (F) (0.50 mmol) and tetrabutylammonium fluoride (0.26 g, 1 mmol) respectively and add them to a 50 mL dry round-bottom flask. Add tetrahydrofuran (10 mL). The reaction mixture was allowed to react at room temperature for 30 min. The reaction was monitored by TLC until the reaction was complete. The mixture was extracted three times with a mixture of water and ethyl acetate. The combined organic layer was washed with brine. The organic phase was collected and dried on anhydrous Na2SO4 until no agglomeration occurred. The crude products (Ⅰ), (Ⅱ), and (Ⅲ) were concentrated under reduced pressure. The crude products were purified by silica gel column chromatography (petroleum ether / ethyl acetate, 1:1, v / v) to obtain a series of compounds (93.2-99.5%).

[0048] The indothiazole derivative synthesized in Example 1 was processed by... 1 H-NMR, 13 C-NMR confirmation was performed, and the specific results are as follows:

[0049] Compound 1

[0050]

[0051] 1 H NMR (400 MHz, DMSO-D6) δ 12.83 (s, 1H), 9.45 – 9.40 (m, 1H), 7.66 (dd, J = 7.6, 1.7 Hz, 1H), 7.61 – 7.51 (m, 2H), 7.47 (td, J = 7.3, 1.5 Hz,1H), 7.34 (dd, J = 8.1, 1.3 Hz, 1H), 7.00 (d, J = 2.1 Hz, 1H), 6.76 (dt, J =8.1, 2.0 Hz, 1H), 3.81 (s, 2H).

[0052] 13 C NMR (101 MHz, DMSO-D6) δ 165.00, 161.51, 156.29, 155.87, 148.44,134.81, 132.47, 130.88, 130.37, 130.03, 128.94, 127.86, 127.78, 118.97,113.96, 113.66, 32.70.

[0053] Compound 2:

[0054]

[0055] 1H NMR (400 MHz, DMSO-D6) δ 12.84 (s, 1H), 9.38 (s, 1H), 8.14 – 8.06 (m, 2H), 7.64 – 7.55 (m, 2H), 7.32 (d, J = 8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.73 (dd, J = 8.1, 2.3 Hz, 1H), 3.78 (s, 2H).

[0056] 13C NMR (101 MHz, DMSO-D6) δ 165.25, 162.15, 158.96, 150.87, 148.32, 135.11, 134.74, 130.28, 130.11, 130.03, 128.45, 127.86, 127.78, 118.97, 113.57, 113.45, 32.70.

[0057] Compound 3:

[0058]

[0059] 1H NMR (400 MHz, DMSO-D6) δ 12.87 (s, 1H), 9.39 (s, 1H), 8.15 (t, J = 1.9 Hz, 1H), 8.04 (ddd, J = 7.8, 1.8, 1.1 Hz, 1H), 7.67 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.74 (dd, J = 8.1, 2.3 Hz, 1H), 3.77 (s, 2H).

[0060] 13C NMR (101 MHz, DMSO-D6) δ 164.32, 162.33, 156.31, 149.95, 148.46, 135.79, 134.23, 133.99, 132.83, 131.11, 130.23, 128.43, 127.33, 118.93, 113.98, 113.68, 32.73.

[0061] Compound 4:

[0062]

[0063] 1H NMR (400 MHz, DMSO-D6) δ 12.81 (s, 1H), 9.42 (d, J = 1.8 Hz, 1H), 7.78 – 7.70 (m, 1H), 7.62 (dd, J = 7.5, 1.9 Hz, 1H), 7.55 – 7.42 (m, 2H), 7.34 (dd, J = 8.1, 1.5 Hz, 1H), 7.01 (d, J = 2.1 Hz, 1H), 6.76 (dt, J = 8.1, 2.1 Hz, 1H), 3.81 (s, 2H).

[0064] 13C NMR (101 MHz, DMSO-D6) δ 165.39, 161.02, 155.79, 155.40, 147.95,136.54, 132.93, 131.99, 129.42, 128.46, 127.73, 127.39, 119.29, 118.48,113.47, 113.17, 32.21.

[0065] Compound 5:

[0066]

[0067] 1H NMR (400 MHz, DMSO-D6) δ 12.90 (s, 1H), 9.42 (s, 1H), 8.32 (t, J =1.8 Hz, 1H), 8.11 (ddd, J = 7.8, 1.7, 1.0 Hz, 1H), 7.83 (ddd, J = 8.0, 2.0,1.0 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.00 (d, J =2.2 Hz, 1H), 6.77 (dd, J = 8.1, 2.3 Hz, 1H), 3.81 (s, 2H).

[0068] 13C NMR (101 MHz, DMSO-D6) δ 166.66, 164.42, 156.31, 155.87, 148.45,135.71, 131.32, 131.21, 127.69, 122.41, 122.05, 121.89, 118.92, 115.68,113.98, 113.68, 32.74.

[0069] Compound 6:

[0070]

[0071] 1H NMR (400 MHz, DMSO-D6) δ 12.89 (s, 1H), 9.42 (s, 1H), 8.03 – 7.91(m, 2H), 7.61 (td, J = 8.0, 5.9 Hz, 1H), 7.50 (tdd, J = 8.4, 2.6, 1.0 Hz,1H), 7.36 (d, J = 8.1 Hz, 1H), 7.00 (d, J = 2.2 Hz, 1H), 6.77 (dd, J = 8.1,2.2 Hz, 1H), 3.82 (s, 2H).

[0072] 13C NMR (101 MHz, DMSO-D6) δ 166.17, 164.35, 155.65, 155.87, 148.45,135.71, 131.45, 131.21, 127.89, 122.35, 122.22, 121.57, 118.79, 115.37,113.69, 113.57, 32.48.

[0073] Compound 7:

[0074]

[0075] 1H NMR (400 MHz, DMSO-D6) δ 12.68 (s, 1H), 9.38 (s, 1H), 7.73 (td, J= 7.5, 1.8 Hz, 1H), 7.59 (dddd, J = 8.4, 7.3, 5.3, 1.8 Hz, 1H), 7.39 – 7.26(m, 3H), 6.97 (d, J = 2.2 Hz, 1H), 6.73 (dd, J = 8.1, 2.3 Hz, 1H), 3.78 (s,2H).

[0076] 13C NMR (101 MHz, DMSO-D6) δ 162.80, 161.14, 158.64, 156.30, 148.45,134.19, 130.86, 128.94, 127.82, 125.15, 122.74, 118.97, 117.02, 116.80,113.96, 113.66, 32.71.

[0077] Compound 8:

[0078]

[0079] 1H NMR (400 MHz, DMSO-D6) δ 12.84 (s, 1H), 9.38 (s, 1H), 8.06 – 7.98 (m, 2H), 7.76 – 7.69 (m, 2H), 7.32 (d, J = 8.1 Hz, 1H), 6.96 (d, J = 2.2 Hz, 1H), 6.73 (dd, J = 8.1, 2.2 Hz, 1H), 3.77 (s, 2H).

[0080] 13C NMR (101 MHz, DMSO-D6) δ 163.35, 161.79, 159.44, 156.57, 148.77,134.89, 131.86, 129.57, 127.52, 125.33, 122.45, 118.97, 117.08, 116.82,113.96, 113.56, 32.78.

[0081] Compound 9:

[0082]

[0083] 1H NMR (400 MHz, DMSO-D6) δ 12.89 (s, 1H), 9.43 (s, 1H), 7.73 – 7.53(m, 2H), 7.42 – 7.29 (m, 2H), 7.01 (d, J = 2.1 Hz, 1H), 6.77 (dd, J = 8.1,2.3 Hz, 1H), 3.82 (s, 2H).

[0084] 13C NMR (101 MHz, DMSO-D6) δ161.21, 161.01, 155.87, 151.04, 150.69,148.51, 147.96, 128.35, 127.50, 125.45, 125.24, 120.62, 120.45, 118.52,113.50, 113.18, 32.25.

[0085] Compound 10:

[0086]

[0087] 1H NMR (400 MHz, DMSO-D6) δ 13.01 (s, 1H), 9.44 (d, J = 2.6 Hz, 1H), 8.18 (dd, J = 8.2, 1.2 Hz, 1H), 7.93 – 7.75 (m, 3H), 7.34 (d, J = 8.2 Hz,1H), 7.01 (d, J = 2.2 Hz, 1H), 6.77 (dd, J = 8.1, 2.2 Hz, 1H), 3.82 (s, 2H).

[0088] 13C NMR (101 MHz, DMSO-D6) δ 164.46, 161.23, 159.87, 156.32, 148.44,147.06, 134.74, 132.25, 130.86, 130.20, 128.89, 127.87, 124.94, 118.97,113.97, 113.67, 32.74.

[0089] Compound 11:

[0090]

[0091] 1H NMR (400 MHz, DMSO-D6) δ 12.34 (s, 1H), 8.57 (s, 1H), 8.09 (t, J =1.9 Hz, 1H), 7.70 – 7.55 (m, 2H), 6.97 (td, J = 8.0, 1.8 Hz, 1H), 6.50 (d, J = 8.1 Hz, 1H), 6.13 (d, J = 2.2 Hz, 1H), 5.91 (dd, J = 8.1, 2.2 Hz, 1H), 2.94 (s, 2H).

[0092] 13C NMR (101 MHz, DMSO-D6) δ 164.48, 161.26, 159.93, 156.42, 148.44,147.25, 134.74, 132.34, 130.86, 130.23, 128.96, 127.89, 124.94, 118.97,113.88, 113.70, 32.74.

[0093] Compound 12:

[0094]

[0095] 1H NMR (400 MHz, DMSO-D6) δ 13.14 (s, 1H), 9.44 (s, 1H), 8.39 – 8.27(m, 4H), 7.36 (d, J = 8.1 Hz, 1H), 7.00 (d, J = 2.1 Hz, 1H), 6.77 (dd, J =8.1, 2.2 Hz, 1H), 3.81 (s, 2H).

[0096] 13C NMR (101 MHz, DMSO-D6) δ 164.53, 161.15, 159.93, 156.23, 148.49,146.99, 134.82, 132.19, 130.95, 130.15, 128.96, 127.79, 125.00, 118.88,114.02, 113.60, 32.82.

[0097] Compound 13:

[0098]

[0099] 1H NMR (400 MHz, DMSO-D6) δ 12.61 (s, 1H), 9.40 (s, 1H), 7.58 (dd, J= 7.5, 1.5 Hz, 1H), 7.43 (td, J = 7.5, 1.5 Hz, 1H), 7.37 – 7.28 (m, 3H), 7.00(d, J = 2.2 Hz, 1H), 6.76 (dd, J = 8.1, 2.2 Hz, 1H), 3.80 (s, 2H), 2.43 (s,3H).

[0100] 13C NMR (101 MHz, DMSO-D6) δ 164.85, 161.83, 155.84, 155.28, 148.02,137.92, 133.24, 131.88, 128.75, 128.60, 128.56, 127.15, 125.26, 118.32,113.54, 113.11, 32.25, 20.86.

[0101] Compound 14:

[0102]

[0103] 1H NMR (400 MHz, DMSO-D6) δ 12.71 (s, 1H), 9.41 (s, 1H), 7.97 (d, J =2.1 Hz, 1H), 7.92 (dt, J = 6.8, 2.2 Hz, 1H), 7.46 – 7.40 (m, 2H), 7.36 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 2.2 Hz, 1H), 6.77 (dd, J = 8.1, 2.2 Hz, 1H), 3.80 (s, 2H), 2.39 (s, 3H).

[0104] 13C NMR (101 MHz, DMSO-D6) δ 164.78, 161.91, 155.75, 155.34, 147.97,138.01, 133.16, 131.95, 128.69,128.61, 128.56, 127.23, 125.19, 118.38,113.45, 113.18, 32.20, 20.94.

[0105] Compound 15:

[0106]

[0107] 1H NMR (400 MHz, DMSO-D6) δ 12.66 (s, 1H), 9.39 (s, 1H), 8.04 – 7.95 (m, 2H), 7.37 – 7.25 (m, 3H), 6.97 (d, J = 2.2 Hz, 1H), 6.75 (dd, J = 8.1,2.3 Hz, 1H), 3.76 (s, 2H), 2.33 (s, 3H).

[0108] 13C NMR (101 MHz, DMSO-D6) δ 165.07, 162.57, 156.24, 155.81, 148.47,143.30, 138.33, 133.58, 129.80, 129.71, 129.13, 128.62, 127.67, 118.87,113.95, 113.67, 32.68, 21.60.

[0109] Compound 16:

[0110]

[0111] 1H NMR (400 MHz, DMSO-D6) δ 12.91 (s, 1H), 9.41 (s, 1H), 7.90 – 7.86 (m, 1H), 7.84 – 7.72 (m, 3H), 7.34 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 2.2 Hz, 1H), 6.76 (dd, J = 8.1, 2.3 Hz, 1H), 3.82 (s, 2H).

[0112] 13C NMR (101 MHz, DMSO-D6) δ 165.19, 161.00, 155.80, 147.94, 133.58,132.61, 130.86, 128.97, 128.41, 127.40, 126.55, 126.45, 125.02, 122.29,118.46, 113.45, 113.16, 32.19.

[0113] Compound 17:

[0114]

[0115] 1H NMR (400 MHz, DMSO-D6) δ 13.17 (s, 1H), 9.40 (s, 1H), 8.93 (t, J =2.0 Hz, 1H), 8.53 – 8.48 (m, 1H), 8.43 (ddd, J = 8.3, 2.4, 1.0 Hz, 1H), 7.82(t, J = 8.0 Hz, 1H), 7.33 (d, J = 8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.74(dd, J = 8.1, 2.3 Hz, 1H), 3.79 (s, 2H).

[0116] 13C NMR (101 MHz, DMSO-D6) δ 165.26, 160.94, 155.88, 147.89, 133.64,132.54, 130.95, 128.93, 128.46, 127.32, 126.61, 126.40, 125.09, 122.23,118.54, 113.38, 113.21, 32.13.

[0117] Compound 18:

[0118]

[0119] 1H NMR (400 MHz, DMSO-D6) δ 13.05 (s, 1H), 9.44 (s, 1H), 8.34 – 8.27(m, 2H), 7.93 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 2.2Hz, 1H), 6.78 (dd, J = 8.1, 2.2 Hz, 1H), 3.82 (s, 2H).

[0120] 13C NMR (101 MHz, DMSO-D6) δ165.18, 162.23, 156.34, 155.45, 148.47,134.78, 133.29, 129.57, 126.12, 126.03, 125.55, 123.18, 122.67, 120.25,118.95, 113.99, 113.69, 32.76.

[0121] Compound 19:

[0122]

[0123] 1H NMR (400 MHz, DMSO-D6) δ 11.91 (s, 1H), 9.41 (s, 1H), 7.76 (dd, J = 7.7, 1.8 Hz, 1H), 7.57 (ddd, J = 8.4, 7.3, 1.9 Hz, 1H), 7.35 (d, J = 8.1Hz, 1H), 7.23 (dd, J = �.6, 1.0 Hz, 1H), 7.10 (td, J = 7.5, 1.0 Hz, 1H), 6.99(d, J = 2.2 Hz, 1H), 6.76 (dd, J = 8.1, 2.3 Hz, 1H), 3.95 (s, 3H), 3.80 (s,2H).

[0124] 13C NMR (101 MHz, DMSO-D6) δ 164.62, 163.08, 162.66, 156.28, 155.68,148.54, 133.50, 132.86, 130.72, 129.10, 127.62, 124.52, 118.78, 114.47,113.86, 113.60, 56.06, 32.60.

[0125] Compound 20:

[0126]

[0127] 1H NMR (400 MHz, DMSO-D6) δ 11.94 (s, 1H), 8.56 (s, 1H), 7.23 (s,0H), 6.92 – 6.82 (m, 2H), 6.61 (t, J = 8.2 Hz, 1H), 6.51 (d, J = 8.1 Hz, 1H),6.34 (ddd, J = 8.2, 2.5, 1.1 Hz, 1H), 6.16 (d, J = 2.1 Hz, 1H), 5.93 (dd, J =8.1, 2.3 Hz, 1H), 3.01 (s, 3H), 2.96 (s, 2H).

[0128] It should be noted that there are some possible typos in the original text (such as "�.6" in the 1H NMR data which should probably be "8.6", and "52" in the 13C NMR data which should probably be "52", and "2" in the 1H NMR data of Compound 20 which should probably be "2"), and they are translated as they are in this translation.13C NMR (101 MHz, DMSO-D6) δ 164.49, 163.22, 162.80, 156.14, 155.82,148.40, 133.64, 132.72, 130.58, 129.24, 127.48, 124.66, 118.92, 114.33,114.00, 113.74, 55.92, 32.74.

[0129] Compound 21:

[0130]

[0131] 1H NMR (400 MHz, DMSO-D6) δ 12.61 (s, 1H), 9.42 (s, 1H), 8.18 – 8.10(m, 2H), 7.37 (d, J = 8.1 Hz, 1H), 7.11 – 7.02 (m, 2H), 7.01 (d, J = 2.2 Hz, 1H), 6.78 (dd, J = 8.1, 2.2 Hz, 1H), 3.83 (s, 3H), 3.79 (d, J = 1.3 Hz, 2H).

[0132] 13C NMR (101 MHz, DMSO-D6) δ 164.56, 163.15, 162.73, 156.21, 155.75,148.47, 133.57, 132.79, 130.65, 129.17, 127.55, 124.59, 118.85, 114.40,113.93, 113.67, 55.99, 32.67.

[0133] Compound 22:

[0134]

[0135] 1H NMR (400 MHz, DMSO-D6) δ 12.50 (s, 1H), 9.36 (s, 1H), 7.29 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.88 (s, 2H), 6.72 (dd, J = 8.1, 2.2Hz, 1H), 3.76 (s, 2H), 2.23 (s, 3H), 2.17 (s, 6H).

[0136] 13C NMR (101 MHz, DMSO-D6) δ 165.14, 162.49, 156.30, 155.74, 148.52,143.24, 138.40, 133.50, 129.86, 129.66, 129.20, 128.56, 127.72, 118.79,114.01, 113.62, 32.75, 21.54, 18.71, 18.70.

[0137] Compound 23:

[0138]

[0139] 1H NMR (400 MHz, DMSO-D6) δ 12.63 (s, 1H), 9.40 (s, 1H), 7.76 (d, J =1.6 Hz, 2H), 7.35 (d, J = 8.1 Hz, 1H), 7.26 (s, 1H), 7.00 (d, J = 2.1 Hz,1H), 6.77 (dd, J = 8.1, 2.2 Hz, 1H), 3.80 (s, 2H), 2.35 (s, 6H).

[0140] 13C NMR (101 MHz, DMSO-D6) δ 165.39, 162.48, 156.23, 155.86, 148.47,138.33, 134.35, 132.42, 129.10, 127.69, 126.35, 121.57, 120.72, 118.85,113.94, 113.67, 32.68, 21.35.

[0141] Compound 24:

[0142]

[0143] 1H NMR (400 MHz, DMSO-D6) δ 11.89 (d, J = 1.4 Hz, 1H), 9.44 – 9.39(m, 1H), 7.83 – 7.76 (m, 1H), 7.56 (ddt, J = 9.7, 7.4, 1.5 Hz, 1H), 7.35 (d,J = 8.1 Hz, 1H), 7.21 (dd, J = 8.5, 1.7 Hz, 1H), 7.15 – 7.06 (m, 1H), 6.99(d, J = 2.2 Hz, 1H), 6.79 – 6.72 (m, 1H), 4.24 (qd, J = 6.9, 1.2 Hz, 2H),3.80 (s, 2H), 1.45 (t, J = 6.9 Hz, 3H).

[0144] 13C NMR (101 MHz, DMSO-D6) δ 163.96, 161.38, 157.06, 156.24, 155.87,148.44, 134.07, 131.00, 128.98, 127.76, 121.85, 121.26, 119.00, 113.93,113.77, 113.63, 65.09, 32.66, 15.09.

[0145] Compound 25:

[0146]

[0147] 1H NMR (400 MHz, DMSO-D6) δ 12.55 (s, 1H), 9.36 (s, 1H), 8.12 – 8.04(m, 2H), 7.32 (d, J = 8.0 Hz, 1H), 7.04 – 6.99 (m, 2H), 6.97 (d, J = 2.2 Hz,1H), 6.73 (dd, J = 8.1, 2.2 Hz, 1H), 4.08 (q, J = 6.9 Hz, 2H), 3.76 (s, 2H),1.31 (t, J = 6.9 Hz, 3H).

[0148] 13C NMR (101 MHz, DMSO-D6) δ 164.56, 162.74, 162.48, 156.21, 155.80,148.46, 133.84, 130.66, 129.15, 127.54, 124.41, 120.08, 118.83, 114.79,113.93, 113.67, 64.03, 32.68, 15.06.

[0149] Compound 26:

[0150]

[0151] 1H NMR (400 MHz, DMSO-D6) δ 12.71 (s, 1H), 9.43 (s, 1H), 8.06 (d, J =8.3 Hz, 2H), 7.37 (dd, J = 8.1, 5.0 Hz, 3H), 7.01 (d, J = 2.1 Hz, 1H), 6.78(dd, J = 8.1, 2.2 Hz, 1H), 3.80 (s, 2H), 2.68 (q, J = 7.6 Hz, 2H), 1.20 (t, J= 7.6 Hz, 3H).

[0152] 13C NMR (101 MHz, DMSO-D6) δ 165.08, 162.55, 156.24, 155.81, 149.39,148.46, 129.97, 129.10, 128.73, 128.55, 127.67, 118.87, 113.95, 113.67,32.69, 28.65, 15.74.

[0153] Compound 27:

[0154]

[0155] 1H NMR (400 MHz, DMSO-D6) δ 12.78 (s, 1H), 9.42 (s, 1H), 8.17 – 8.10(m, 2H), 7.67 – 7.60 (m, 1H), 7.55 (dd, J = 8.2, 6.8 Hz, 2H), 7.36 (d, J =8.1 Hz, 1H), 7.01 (d, J = 2.2 Hz, 1H), 6.77 (dd, J = 8.1, 2.2 Hz, 1H), 3.81(s, 2H).

[0156] 13C NMR (101 MHz, DMSO-D6) δ 165.55, 162.45, 156.27, 151.07, 148.46,133.09, 132.51, 129.16, 129.04, 128.60, 128.34, 127.98, 127.77, 118.89,113.96, 113.68, 32.71.

[0157] Compound 28:

[0158]

[0159] 1H NMR (400 MHz, DMSO-D6) δ 12.50 (s, 1H), 9.40 (s, 1H), 7.36 – 7.26(m, 3H), 7.03 – 6.94 (m, 4H), 6.76 (dd, J = 8.1, 2.2 Hz, 1H), 3.77 (s, 2H).

[0160] 13C NMR (101 MHz, DMSO-D6) δ 167.12, 161.25, 158.23, 156.25, 148.38,130.07, 128.95, 127.54, 121.76, 118.90, 115.06, 113.93, 113.65, 32.67.

[0161] Compound 29:

[0162]

[0163] 1H NMR (400 MHz, DMSO-D6) δ 12.95 (s, 1H), 9.42 (s, 1H), 7.89 – 7.80(m, 2H), 7.55 (tt, J = 9.1, 2.4 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.00 (d, J = 2.1 Hz, 1H), 6.77 (dd, J = 8.1, 2.2 Hz, 1H), 3.80 (s, 2H).

[0164] 13C NMR (101 MHz, DMSO-D6) δ 164.08, 163.95, 161.62, 161.49, 159.45,156.36, 148.44, 128.91, 128.03, 118.95, 113.99, 113.67, 112.15, 111.96,108.48, 108.23, 32.74.

[0165] Compound 30:

[0166]

[0167] 1H NMR (400 MHz, DMSO-D6) δ 12.99 (s, 1H), 9.44 (s, 1H), 8.14 (d, J =1.9 Hz, 2H), 7.90 (t, J = 1.9 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.00 (d, J =2.3 Hz, 1H), 6.77 (dd, J = 8.1, 2.2 Hz, 1H), 3.81 (s, 2H).

[0168] 13C NMR (101 MHz, DMSO-D6) δ 164.15, 163.89, 161.70, 161.42, 159.51,156.28, 148.51, 128.85, 128.11, 118.88, 114.05, 113.59, 112.22, 111.90,108.56, 108.16, 32.80.

[0169] Compound 31:

[0170]

[0171] 1H NMR (400 MHz, DMSO-D6) δ 12.89 (s, 1H), 9.42 (s, 1H), 7.79 (d, J =2.0 Hz, 1H), 7.71 (d, J = 8.3 Hz, 1H), 7.57 (dd, J = 8.3, 2.0 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.00 (d, J = 2.1 Hz, 1H), 6.76 (dd, J = 8.1, 2.2 Hz, 1H), 3.82 (s, 2H).

[0172] 13C NMR (101 MHz, DMSO-D6) δ 164.22, 163.82, 161.78, 161.34, 159.58,156.21, 148.59, 128.77, 128.18, 118.81, 114.13, 113.51, 112.29, 111.83,108.64, 108.08, 32.87.

[0173] Compound 32:

[0174]

[0175] 1H NMR (400 MHz, DMSO-D6) δ 12.85 (s, 1H), 9.42 (s, 1H), 7.76 (dd, J= 8.6, 6.1 Hz, 1H), 7.61 (dd, J = 9.0, 2.5 Hz, 1H), 7.41 – 7.30 (m, 2H), 7.00(d, J = 2.3 Hz, 1H), 6.76 (dd, J = 8.1, 2.3 Hz, 1H), 3.81 (s, 2H).

[0176] 13C NMR (101 MHz, DMSO-D6) δ 164.03, 161.50, 155.81, 155.34, 147.93,132.08, 131.97, 131.59, 131.49, 131.00, 128.40, 127.39, 118.47, 117.52,114.70, 113.16, 32.21.

[0177] Compound 33:

[0178]

[0179] 1H NMR (400 MHz, DMSO-D6) δ 12.24 (s, 1H), 9.39 (s, 1H), 7.30 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.75 (dd, J = 8.1, 2.2 Hz, 1H), 3.74(s, 2H), 2.14(s, 3H).

[0180] 13C NMR (101 MHz, DMSO-D6) δ 168.20, 161.49, 155.67, 155.01, 147.90,128.62, 126.50, 118.31, 113.39, 113.14, 32.11, 22.58.

[0181] Compound 34:

[0182]

[0183] 1H NMR (400 MHz, DMSO-D6) δ 12.18 (s, 1H), 9.38 (s, 1H), 7.30 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.3 Hz, 1H), 6.74 (dd, J = 8.1, 2.2 Hz, 1H), 3.75(s, 2H), 2.44 (q, J = 7.5 Hz, 2H), 1.10 (t, J = 7.5 Hz, 3H).

[0184] 13C NMR (101 MHz, DMSO-D6) δ 171.83, 161.52, 155.64, 155.01, 147.88,128.64, 126.43, 118.27, 113.37, 113.13, 32.10, 28.29, 9.18.

[0185] Compound 35:

[0186]

[0187] 1H NMR (400 MHz, DMSO-D6) δ 12.20 (s, 1H), 9.38 (s, 1H), 7.30 (d, J =8.1 Hz, 1H), 6.98 (d, J = 2.2 Hz, 1H), 6.75 (dd, J = 8.1, 2.2 Hz, 1H), 3.74(s, 2H), 2.40 (t, J = 7.3 Hz, 2H), 1.63 (h, J = 7.4 Hz, 2H), 0.90 (t, J = 7.4Hz, 3H).

[0188] 13C NMR (101 MHz, DMSO-D6) δ 171.01, 161.46, 155.66, 155.02, 147.90,128.64, 126.48, 118.28, 113.38, 113.14, 36.88, 32.11, 18.22, 13.58.

[0189] Compound 36:

[0190]

[0191] 1H NMR (400 MHz, DMSO-D6) δ 12.16 (s, 1H), 9.35 (s, 1H), 7.26 (d, J =8.1 Hz, 1H), 6.93 (d, J = 2.2 Hz, 1H), 6.70 (dd, J = 8.1, 2.3 Hz, 1H), 3.71(s, 2H), 2.39 (t, J = 7.4 Hz, 2H), 1.61 – 1.49 (m, 2H), 1.34 – 1.20 (m, 2H), 0.85 (t, J = 7.3 Hz, 3H).

[0192] 13C NMR (101 MHz, DMSO-D6) δ 171.15, 161.46, 155.65, 155.01, 147.90,128.63, 126.48, 118.28, 113.37, 113.13, 34.68, 32.11, 26.85, 21.74, 13.71.

[0193] Compound 37:

[0194]

[0195] 1H NMR (400 MHz, DMSO-D6) δ 12.20 (s, 1H), 9.39 (s, 1H), 7.30 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.74 (dd, J = 8.1, 2.2 Hz, 1H), 3.75(s, 2H), 2.42 (t, J = 7.4 Hz, 2H), 1.60 (p, J = 7.3 Hz, 2H), 1.28 (q, J = 3.4Hz, 4H), 0.91 – 0.82 (m, 3H).

[0196] 13C NMR (101 MHz, DMSO-D6) δ 171.17, 161.46, 155.65, 155.01, 147.90,128.63, 126.49, 118.29, 113.38, 113.14, 34.94, 32.12, 30.79, 24.43, 21.88,13.88.

[0197] Compound 38:

[0198]

[0199] 1H NMR (400 MHz, DMSO-D6) δ 12.18 (s, 1H), 9.36 (s, 1H), 7.30 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.74 (dd, J = 8.1, 2.2 Hz, 1H), 3.75(s, 2H), 2.42 (t, J = 7.4 Hz, 2H), 1.60 (p, J = 6.8 Hz, 2H), 1.33 – 1.22 (m,6H), 0.90 – 0.82 (m, 3H).

[0200] 13C NMR (101 MHz, DMSO-D6) δ 171.10, 161.42, 155.62, 154.99, 147.84,128.60, 126.42, 118.23, 113.34, 113.09, 34.95, 32.06, 30.94, 28.20, 24.66,21.95, 13.92.

[0201] Compound 39:

[0202]

[0203] 1H NMR (400 MHz, DMSO-D6) δ 12.15 (s, 1H), 9.34 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.71 (dd, J = 8.1, 2.3 Hz, 1H), 3.71(s, 2H), 2.38 (t, J = 7.4 Hz, 2H), 1.56 (p, J = 7.4 Hz, 2H), 1.28 – 1.17 (m, 8H), 0.85 – 0.76 (m, 3H).

[0204] 13C NMR (101 MHz, DMSO-D6) δ 171.63, 161.95, 156.14, 155.51, 148.37, 129.12, 126.95, 118.76, 113.86, 113.62, 35.46, 32.59, 31.65, 29.03, 28.91, 25.23, 22.59, 14.47.

[0205] Compound 40:

[0206]

[0207] 1H NMR (400 MHz, DMSO-D6) δ 12.15 (s, 1H), 9.34 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.71 (dd, J = 8.1, 2.3 Hz, 1H), 3.70(s, 2H), 2.37 (t, J = 7.4 Hz, 2H), 1.55 (p, J = 7.4 Hz, 2H), 1.21 (dd, J = 10.2, 3.6 Hz, 12H), 0.84 – 0.75 (m, 3H).

[0208] 13C NMR (101 MHz, DMSO-D6) δ 171.13, 161.45, 155.65, 155.01, 147.87,128.63, 126.44, 118.26, 113.36, 113.12, 34.97, 32.09, 31.29, 28.72, 28.59,28.57, 24.72, 22.12, 13.98.

[0209] Compound 41:

[0210]

[0211] 1H NMR (400 MHz, DMSO-D6) δ 12.20 (s, 1H), 9.39 (s, 1H), 7.29 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.2 Hz, 1H), 6.74 (dd, J = 8.1, 2.2 Hz, 1H), 3.74(s, 2H), 2.41 (t, J = 7.4 Hz, 2H), 1.58 (q, J = 7.0 Hz, 2H), 1.24 (d, J = 9.5Hz, 12H), 0.87 – 0.79 (m, 3H).

[0212] 13C NMR (101 MHz, DMSO-D6) δ 171.14, 161.46, 155.66, 155.02, 147.88,128.64, 126.45, 118.27, 113.37, 113.13, 34.98, 32.11, 31.33, 28.91, 28.78,28.74, 28.58, 24.74, 22.17, 14.01.

[0213] Compound 42:

[0214]

[0215] 1H NMR (400 MHz, DMSO-D6) δ 12.18 (s, 1H), 9.37 (s, 1H), 7.29 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.3 Hz, 1H), 6.74 (dd, J = 8.1, 2.2 Hz, 1H), 3.74(s, 2H), 2.41 (t, J = 7.4 Hz, 2H), 1.59 (p, J = 7.6 Hz, 2H), 1.22 (s, 14H), 0.87 – 0.78 (m, 3H).

[0216] 13C NMR (101 MHz, DMSO-D6) δ 171.12, 161.45, 155.64, 155.02, 147.86,128.63, 126.43, 118.25, 113.36, 113.11, 34.96, 32.09, 31.34, 29.05, 29.02,28.92, 28.77, 28.73, 28.55, 24.71, 22.14, 13.97.

[0217] Compound 43:

[0218]

[0219] 1H NMR (400 MHz, DMSO-D6) δ 12.48 (s, 1H), 9.34 (s, 1H), 7.27 (d, J =8.1 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.71 (dd, J = 8.1, 2.3 Hz, 1H), 3.70(s, 2H), 1.95 – 1.84 (m, 1H), 0.87 (d, J = 5.4 Hz, 4H).

[0220] 13C NMR (101 MHz, DMSO-D6) δ 173.18, 162.02, 156.20, 155.48, 148.43,129.06, 127.10, 118.70, 113.92, 113.55, 32.55, 25.08, 18.23.

[0221] Compound 44:

[0222]

[0223] 1H NMR (400 MHz, DMSO-D6) δ 12.06 (s, 1H), 9.34 (s, 1H), 7.25 (d, J =8.1 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.71 (dd, J = 8.1, 2.2 Hz, 1H), 3.71(s, 2H), 3.33 – 3.25 (m, 1H), 2.27 – 2.18 (m, 2H), 2.14 – 2.05 (m, 2H), 2.01 – 1.84 (m, 1H), 1.84 – 1.72 (m, 1H).

[0224] 13C NMR (101 MHz, DMSO-D6) δ 173.11, 162.08, 156.14, 155.55, 148.37,129.13, 127.04, 118.76, 113.86, 113.62, 38.85, 32.61, 25.02, 18.29.

[0225] Compound 45:

[0226]

[0227] 1H NMR (400 MHz, DMSO-D6) δ 12.17 (s, 1H), 9.34 (s, 1H), 7.26 (d, J =8.1 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.71 (dd, J = 8.1, 2.3 Hz, 1H), 3.71(s, 2H), 2.87 (p, J = 7.9 Hz, 1H), 1.90 – 1.78 (m, 2H), 1.75 – 1.44 (m, 6H).

[0228] 13C NMR (101 MHz, DMSO-D6) δ 173.18, 162.02, 156.22, 155.48, 148.46,129.05, 127.10, 118.71, 113.94, 113.55, 38.94, 32.55, 25.09, 18.21.

[0229] Compound 46:

[0230]

[0231] 1H NMR (400 MHz, DMSO-D6) δ 12.11 (s, 1H), 9.33 (d, J = 0.9 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 6.93 (d, J = 2.2 Hz, 1H), 6.70 (dd, J = 8.1, 2.2Hz, 1H), 3.71 (s, 2H), 2.42 (dt, J = 11.5, 3.6 Hz, 1H), 1.82 – 1.66 (m, 5H), 1.44 – 1.30 (m, 2H), 1.29 – 1.09 (m, 3H).

[0232] 13C NMR (101 MHz, DMSO-D6) δ 173.25, 161.95, 156.28, 155.42, 148.51,129.00, 127.16, 118.65, 113.99, 113.50, 39.00, 32.49, 25.14, 24.32, 18.16.

[0233] Compound 47:

[0234]

[0235] 1H NMR (400 MHz, DMSO-D6) δ 12.65 (s, 1H), 9.41 (s, 1H), 7.32 (d, J =8.1 Hz, 1H), 6.98 (d, J = 2.2 Hz, 1H), 6.75 (dd, J = 8.1, 2.3 Hz, 1H), 4.39(s, 2H), 3.78(s, 2H).

[0236] 13C NMR (101 MHz, DMSO-D6) δ 164.81, 160.79, 155.78, 155.32, 147.85,128.34, 127.27, 118.42, 113.42, 113.12, 42.34, 32.18.

[0237] Compound 48:

[0238]

[0239] 1H NMR (400 MHz, DMSO-D6) δ 12.43 (s, 1H), 9.57 (s, 1H), 7.28 (d, J =8.1 Hz, 1H), 6.98 (d, J = 2.2 Hz, 1H), 6.70 (dd, J = 8.1, 2.3 Hz, 1H), 3.78(s, 2H).

[0240] 13C NMR (101 MHz, DMSO-D6) δ 164.88, 160.73, 155.86, 155.25, 147.91,128.26, 127.34, 118.36, 113.50, 113.05, 95.37, 32.10.

[0241] Compound 49:

[0242]

[0243] 1H NMR (400 MHz, DMSO-D6) δ 12.16 (s, 1H), 9.32 (s, 1H), 7.26 (d, J =8.1 Hz, 1H), 6.94 (d, J = 2.1 Hz, 1H), 6.71 (dd, J = 8.1, 2.2 Hz, 1H), 3.71(s, 2H), 3.31 (d, J = 3.2 Hz, 1H), 2.40 (t, J = 7.5 Hz, 2H), 1.75 – 1.64 (m,3H), 1.58 (q, J = 7.2 Hz, 2H), 1.54 – 1.37 (m, 3H), 1.09 – 0.99 (m, 2H).

[0244] 13C NMR (101 MHz, DMSO-D6) δ 171.71, 161.98, 156.15, 155.53, 148.37,129.14, 126.96, 118.76, 113.87, 113.62, 39.69, 34.88, 32.59, 32.51, 31.51,25.21.

[0245] Compound 50:

[0246]

[0247] 1H NMR (400 MHz, DMSO-D6) δ 12.19 (s, 1H), 9.36 (s, 1H), 7.30 (d, J =8.1 Hz, 1H), 6.97 (d, J = 2.1 Hz, 1H), 6.74 (dd, J = 8.1, 2.3 Hz, 1H), 3.74(s, 2H), 2.43 (t, J = 7.7 Hz, 2H), 1.74 – 1.58 (m, 5H), 1.50 (q, J = 7.3 Hz, 2H), 1.22 – 1.11 (m, 2H), 0.94 – 0.82 (m, 2H).

[0248] 13C NMR (101 MHz, DMSO-D6) δ 171.32, 161.45, 155.62, 154.99, 147.84,128.60, 126.42, 118.22, 113.34, 113.09, 36.64, 32.55, 32.51, 32.18, 32.15,32.06, 26.08, 25.72.

[0249] Compound 51:

[0250]

[0251] 1H NMR (400 MHz, DMSO-D6) δ 11.82 (s, 1H), 9.36 (s, 1H), 7.30 (d, J =8.1 Hz, 1H), 6.98 (d, J = 2.1 Hz, 1H), 6.75 (dd, J = 8.1, 2.2 Hz, 1H), 3.75(s, 2H), 2.00 (q, J = 3.1 Hz, 3H), 1.94 (d, J = 3.0 Hz, 6H), 1.70 (d, J = 3.1Hz, 6H).

[0252] 13C NMR (101 MHz, DMSO-D6) δ 175.83, 162.07, 155.61, 155.00, 147.87,128.69, 126.57, 118.17, 113.35, 113.11, 40.57, 37.62, 35.80, 32.08, 27.52.

[0253] Compound 52:

[0254]

[0255] 1H NMR (400 MHz, DMSO-D6) δ 12.50 (s, 1H), 9.40 (s, 1H), 7.36 – 7.26 (m, 3H), 7.03 – 6.94 (m, 4H), 6.76 (dd, J = 8.1, 2.2 Hz, 1H), 4.86 (s, 2H),3.77 (s, 2H).

[0256] 13C NMR (101 MHz, DMSO-D6) δ 167.12, 161.25, 158.23, 156.25, 148.38,130.07, 128.95, 127.54, 121.76, 118.90, 115.06, 113.93, 113.65, 66.52, 32.67.

[0257] Compound 53:

[0258]

[0259] 1H NMR (400 MHz, DMSO-D6) δ 12.36 (s, 1H), 9.40 (s, 1H), 7.31 (d, J =8.1 Hz, 1H), 6.97 (s, 1H), 6.73 (d, J = 8.2 Hz, 1H), 3.76 (s, 2H), 2.57 (s,3H), 2.34 (s,3H).

[0260] 13C NMR (101 MHz, DMSO-D6) δ 167.19, 161.19, 160.05, 158.31, 156.18,145.44, 144.37, 131.02, 127.48, 121.84, 118.83, 115.12, 113.85, 32.73. 16.45,16.23,

[0261] Compound 54:

[0262]

[0263] 1H NMR (400 MHz, DMSO-D6) δ 12.74 (s, 1H), 9.42 (s, 1H), 8.04 – 7.99(m, 1H), 7.68 (d, J = 3.6 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.00 (d, J = 2.2Hz, 1H), 6.77 (dd, J = 8.1, 2.3 Hz, 1H), 6.74 (dd, J = 3.6, 1.7 Hz, 1H), 3.80(s, 2H).

[0264] 13C NMR (101 MHz, DMSO-D6) δ 162.57, 155.77, 155.31, 147.94, 147.28,145.59, 128.48, 127.20, 122.35, 118.37, 116.27, 113.45, 113.18, 112.33,32.21.

[0265] Compound 55:

[0266]

[0267] 1H NMR (400 MHz, DMSO-D6) δ 12.98 (s, 1H), 9.40 (s, 1H), 7.32 (d, J =8.2 Hz, 1H), 6.97 (d, J = 2.1 Hz, 1H), 6.80 (d, J = 1.1 Hz, 1H), 6.74 (dd, J = 8.1, 2.3 Hz, 1H), 3.78 (s, 2H), 2.46 (d, J = 2.8 Hz, 3H).

[0268] 13C NMR (101 MHz, DMSO-D6) δ 172.16, 162.23, 162.12, 158.16, 157.82,156.39, 148.44, 128.74, 128.34, 119.05, 114.02, 113.68, 102.05, 32.76, 12.46.

[0269] Compound 56:

[0270]

[0271] 1H NMR (400 MHz, DMSO-D6) δ 12.87 (s, 1H), 9.42 (s, 1H), 8.26 (d, J =3.2 Hz, 1H), 7.96 (dd, J = 5.0, 1.1 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.25(dd, J = 5.0, 3.8 Hz, 1H), 7.00 (d, J = 2.2 Hz, 1H), 6.77 (dd, J = 8.1, 2.2Hz, 1H), 3.80 (s, 2H).

[0272] 13C NMR (101 MHz, DMSO-D6) δ 162.21, 159.83, 155.79, 147.95, 137.21,135.03, 134.56, 132.67, 130.66, 128.67, 127.67, 118.38, 113.47, 113.19,32.25.

[0273] Compound 57:

[0274]

[0275] 1H NMR (400 MHz, DMSO-D6) δ 12.98 (s, 1H), 9.43 (s, 1H), 8.11 (s,1H), 7.35 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 3.7 Hz, 1H), 7.00 (d, J = 2.2 Hz,1H), 6.77 (dd, J = 8.1, 2.2 Hz, 1H), 3.79 (s, 2H).

[0276] 13C NMR (101 MHz, DMSO-D6) δ 162.12, 159.34, 156.36, 149.62, 148.42,147.23, 140.65, 135.72, 131.17, 130.23, 129.31, 118.92, 113.99, 113.69,32.80.

[0277] Compound 58:

[0278]

[0279] 1H NMR (400 MHz, DMSO-D6) δ 12.97 (s, 1H), 9.42 (s, 1H), 8.56 (dd, J = 4.8, 1.9 Hz, 1H), 8.16 (dd, J = 7.6, 1.9 Hz, 1H), 7.58 (dd, J = 7.6, 4.9 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 2.2 Hz, 1H), 6.77 (dd, J = 8.1, 2.3 Hz, 1H), 3.82 (s, 2H).

[0280] 13C NMR (101 MHz, DMSO-D6) δ 162.27, 159.59, 156.45, 154.04, 150.38, 148.39, 148.38, 139.79, 139.89, 136.44, 126.89, 124.78, 119.02, 113.94, 113.76, 32.72.

[0281] Compound 59:

[0282]

[0283] 1H NMR (400 MHz, DMSO-D6) δ 13.09 (s, 1H), 9.44 (s, 1H), 9.08 (dd, J = 2.5, 0.8 Hz, 1H), 8.48 (dd, J = 8.4, 2.5 Hz, 1H), 7.73 (dd, J = 8.4, 0.7 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.00 (d, J = 2.2 Hz, 1H), 6.77 (dd, J = 8.1, 2.3 Hz, 1H), 3.82 (s, 2H).

[0284] 13C NMR (101 MHz, DMSO-D6) δ 162.20, 159.66, 156.37, 154.12, 150.31, 148.46, 148.32, 139.85, 139.82, 136.51, 126.81, 124.86, 118.96, 114.00, 113.69, 32.79.

[0285] Compound 60:

[0286]

[0287] 1H NMR (400 MHz, DMSO-D6) δ 12.25 (s, 1H), 9.38 (d, J = 0.9 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.03 (d, J = 2.2 Hz, 1H), 6.85 (dd, J = 8.1, 2.2Hz, 1H), 3.71 (s, 2H), 3.53 (q, J = 3.4 Hz, 4H), 1.82 – 1.66 (m, 4H), 1.44 –1.30 (m, 2H).

[0288] 13C NMR (101 MHz, DMSO-D6) δ 173.25, 161.95, 156.28, 155.42, 148.51,129.00, 127.16, 118.65, 113.99, 113.50, 52.00, 32.49, 25.14, 24.32.

[0289] Compound 61:

[0290]

[0291] 1H NMR (400 MHz, DMSO-D6) δ 9.30 (s, 1H), 7.64 (s, 1H), 7.40 – 7.33(m, 1H), 7.33 – 7.21 (m, 4H), 7.06 (s, 1H), 6.77 (s, 1H), 6.48 (s, 1H), 4.70 (d, J = 1.2 Hz, 2H), 3.96 (s, 2H).

[0292] 13C NMR (101 MHz, DMSO-D6) δ 165.01, 159.63, 142.15, 141.79, 137.20,133.26, 132.11, 131.33, 130.81, 129.98, 127.82, 123.69, 121.97, 114.84,111.55, 52.41, 34.60.

[0293] Compound 62:

[0294]

[0295] 1H NMR (400 MHz, DMSO-D6) δ 9.28 (s, 1H), 7.64 (s, 1H), 7.48 (tt, J =2.1, 0.9 Hz, 1H), 7.39 (dt, J = 7.3, 2.1 Hz, 1H), 7.28 (dtt, J = 7.5, 2.1,1.1 Hz, 1H), 7.23 (t, J = 7.4 Hz, 1H), 7.06 (s, 1H), 6.77 (s, 1H), 6.66 (s,1H), 4.80 (d, J = 1.5 Hz, 2H), 3.96 (s, 1H).

[0296] 13C NMR (101 MHz, DMSO-D6) δ 166.19, 159.63, 142.15, 141.79, 134.90,134.61, 134.47, 132.46, 131.72, 129.05, 123.69, 122.39, 121.97, 114.84,111.55, 52.93, 34.60.

[0297] Compound 63:

[0298]

[0299] 1H NMR (400 MHz, DMSO-D6) δ 9.35 (s, 1H), 7.64 (s, 1H), 7.39 – 7.30(m, 2H), 7.25 (ddq, J = 7.5, 2.0, 1.0 Hz, 1H), 7.07 – 6.98 (m, 3H), 6.77 (s,1H), 6.62 (s, 1H), 4.74 – 4.70 (m, 2H), 3.96 (s, 2H).

[0300] 13C NMR (101 MHz, DMSO-D6) δ 166.09, 164.52, 159.63, 142.15, 141.79,132.93, 132.55, 130.69, 129.05, 123.69, 121.97, 118.01, 117.69, 114.84,111.55, 52.81, 34.60.

[0301] Compound 64:

[0302]

[0303] 1H NMR (400 MHz, DMSO-D6) δ 9.16 (s, 1H), 7.64 (s, 1H), 7.53 (dd, J =7.4, 2.1 Hz, 1H), 7.50 – 7.41 (m, 2H), 7.22 (td, J = 7.5, 2.1 Hz, 1H), 7.06(s, 1H), 6.77 (s, 1H), 6.67 (s, 1H), 4.75 (t, J = 0.7 Hz, 2H), 3.96 (s, 2H).

[0304] 13C NMR (101 MHz, DMSO-D6) δ 166.70, 159.63, 142.15, 141.79, 133.53,131.43, 129.71, 129.05, 128.83, 127.19, 126.09, 125.59, 123.69, 121.97,114.84, 111.55, 50.54, 34.60.

[0305] Compound 65:

[0306]

[0307] 1H NMR (400 MHz, DMSO-D6) δ 9.30 (s, 1H), 7.74 (tt, J = 2.1, 1.1 Hz,1H), 7.64 (s, 1H), 7.56 (dt, J = 7.5, 2.0 Hz, 1H), 7.50 (t, J = 7.5 Hz, 1H),7.33 (dtt, J = 7.5, 2.1, 1.0 Hz, 1H), 7.06 (s, 1H), 6.77 (s, 1H), 6.66 (s,1H), 4.77 – 4.73 (m, 2H), 3.96 (s, 2H).

[0308] 13C NMR (101 MHz, DMSO-D6) δ 166.19, 159.63, 142.15, 141.79, 136.41,133.82, 131.07, 130.56, 129.17, 129.05, 127.63, 126.52, 123.69, 121.97,114.84, 111.55, 52.81, 34.60.

[0309] Compound 66:

[0310]

[0311] 1H NMR (400 MHz, DMSO-D6) δ 9.27 (s, 1H), 7.64 (s, 1H), 7.60 – 7.54(m, 2H), 7.46 – 7.40 (m, 2H), 7.06 (s, 1H), 6.76 (d, J = 6.7 Hz, 2H), 4.75(d, J = 1.5 Hz, 2H), 3.96 (s, 2H).

[0312] 13C NMR (101 MHz, DMSO-D6) δ 166.19, 159.63, 142.15, 141.79, 138.72,132.47, 131.58, 129.05, 127.10, 126.31, 123.69, 121.97, 114.84, 111.55,52.23, 34.60.

[0313] Compound 67:

[0314]

[0315] 1H NMR (400 MHz, DMSO-D6) δ 9.31 (s, 1H), 7.37 (s, 1H), 7.24 – 7.16 (m, 2H), 7.18 – 7.06 (m, 3H), 6.77 (s, 1H), 6.39 (s, 1H), 4.71 (d, J = 1.2Hz, 2H), 3.96 (s, 2H).

[0316] 13C NMR (101 MHz, DMSO-D6) δ 165.83, 159.63, 142.15, 141.79, 140.72,134.25, 131.40, 130.72, 129.05, 128.81, 123.69, 121.97, 114.84, 111.55,51.59, 34.60, 21.12.

[0317] Compound 68:

[0318]

[0319] 1H NMR (400 MHz, DMSO-D6) δ 9.28 (s, 1H), 7.64 (s, 1H), 7.23 (dtt, J= 7.2, 2.0, 1.0 Hz, 1H), 7.12 (dd, J = 7.9, 7.2 Hz, 1H), 7.12 – 7.07 (m, 2H),7.06 (s, 1H), 6.77 (s, 1H), 6.66 (s, 1H), 4.72 (q, J = 0.7 Hz, 2H), 3.96 (s,2H), 2.31 (d, J = 2.0 Hz, 1H).

[0320] 13C NMR (101 MHz, DMSO-D6) δ 166.19, 159.63, 142.15, 141.79, 138.24,135.42, 131.25, 131.10, 130.85, 130.72, 129.05, 123.69, 121.97, 114.84,111.55, 52.54, 34.60, 22.21.

[0321] Compound 69:

[0322]

[0323] 1H NMR (400 MHz, DMSO-D6) δ 9.30 (s, 1H), 7.64 (s, 1H), 7.20 (dp, J =7.3, 1.3 Hz, 2H), 7.09 (dq, J = 7.5, 1.1 Hz, 2H), 7.06 (s, 1H), 6.76 (d, J =6.8 Hz, 2H), 4.76 (d, J = 1.5 Hz, 2H), 3.96 (s, 2H), 2.37 (d, J = 1.9 Hz, 1H).

[0324] 13C NMR (101 MHz, DMSO-D6) δ 166.19, 159.63, 142.15, 141.79, 139.31,135.24, 131.38, 131.01, 129.05, 123.69, 121.97, 114.84, 111.55, 52.23, 34.60,22.35.

[0325] Compound 70:

[0326]

[0327] 1H NMR (400 MHz, DMSO-D6) δ 9.27 (s, 1H), 7.64 (s, 1H), 7.43 (s, 1H), 7.32 (ddt, J = 7.4, 2.0, 1.1 Hz, 1H), 7.20 (td, J = 7.5, 2.0 Hz, 1H), 7.05 (s, 1H), 7.04 (td, J = 7.5, 2.0 Hz, 1H), 6.88 (dd, J = 7.5, 2.0 Hz, 1H), 6.77 (s, 1H), 4.81 (d, J = 1.2 Hz, 2H), 3.96 (s, 1H), 3.81 (s, 2H).

[0328] 13C NMR (101 MHz, DMSO-D6) δ 168.66, 161.48, 159.63, 142.15, 141.79, 132.21, 130.96, 129.98, 126.36, 123.89, 123.69, 121.97, 114.84, 112.60, 111.55, 56.07, 53.20, 34.60.

[0329] Compound 71:

[0330]

[0331] 1H NMR (400 MHz, DMSO-D6) δ 9.31 (s, 1H), 7.64 (s, 1H), 7.24 – 7.17 (m, 2H), 7.06 (s, 1H), 6.91 – 6.85 (m, 2H), 6.76 (d, J = 6.7 Hz, 2H), 4.77 (d, J = 1.1 Hz, 2H), 3.96 (s, 1H), 3.79 (s, 2H).

[0332] 13C NMR (101 MHz, DMSO-D6) δ 166.19, 161.42, 159.63, 142.15, 141.79, 132.14, 130.73, 129.05, 123.69, 121.97, 115.04, 114.84, 111.55, 56.03, 52.19, 34.60.

[0333] Compound 72:

[0334]

[0335] 1H NMR (400 MHz, DMSO-D6) δ 9.28 (s, 1H), 7.64 (s, 0H), 7.17 – 7.08(m, 2H), 7.06 (s, 0H), 6.76 (d, J = 6.8 Hz, 1H), 4.75 (q, J = 0.8 Hz, 1H), 3.96 (s, 1H), 2.66 (t, J = 1.0 Hz, 1H), 1.22 (s, 1H).

[0336] 13C NMR (101 MHz, DMSO-D6) δ 166.19, 159.63, 145.25, 142.15, 141.79,135.57, 131.65, 130.36, 129.05, 123.69, 121.97, 114.84, 111.55, 52.23, 34.60,30.39, 15.93.

[0337] Compound 73:

[0338]

[0339] 1H NMR (400 MHz, DMSO-D6) δ 9.30 (s, 1H), 7.64 (s, 1H), 7.23 – 7.16(m, 3H), 7.06 (s, 1H), 6.92 (s, 1H), 6.77 (s, 1H), 4.77 (d, J = 1.2 Hz, 2H),3.96 (s, 2H).

[0340] 13C NMR (101 MHz, DMSO-D6) δ 166.09, 159.63, 142.15, 141.79, 133.98,133.26, 131.48, 129.93, 129.05, 123.69, 121.97, 114.84, 111.55, 50.62, 34.60.

[0341] Compound 74:

[0342]

[0343] 1H NMR (400 MHz, DMSO-D6) δ 9.28 (s, 1H), 7.64 (s, 1H), 7.06 (s, 1H), 6.99 (dt, J = 2.0, 1.0 Hz, 2H), 6.92 – 6.85 (m, 2H), 6.77 (s, 1H), 4.74 (d, J= 1.1 Hz, 2H), 3.96 (s, 2H).

[0344] 13C NMR (101 MHz, DMSO-D6) δ 165.38, 163.58, 159.63, 142.15, 141.79,131.05, 129.05, 123.69, 121.97, 117.09, 114.84, 111.55, 107.52, 54.17, 34.60.

[0345] Compound 75:

[0346]

[0347] 1H NMR (400 MHz, DMSO-D6) δ 9.31 (s, 1H), 7.64 (s, 1H), 7.40 (s, 1H), 7.38 – 7.31 (m, 2H), 7.25 (d, J = 7.5 Hz, 1H), 7.15 (dd, J = 7.5, 2.0 Hz, 1H), 7.06 (s, 1H), 6.77 (s, 1H), 4.95 (d, J = 1.3 Hz, 1H), 3.96 (s, 2H).

[0348] 13C NMR (101 MHz, DMSO-D6) δ 168.81, 159.63, 152.44, 150.81, 142.15,141.79, 131.39, 129.98, 128.78, 123.69, 121.97, 120.55, 117.19, 114.84,111.55, 49.33, 34.60.

[0349] Compound 76:

[0350]

[0351] 1H NMR (400 MHz, DMSO-D6) δ 12.64 (s, 1H), 9.26 (s, 1H), 7.90 – 7.84(m, 1H), 7.64 (s, 1H), 7.58 – 7.51 (m, 2H), 7.44 – 7.37 (m, 1H), 7.06 (s,1H), 6.77 (s, 1H), 4.00 (s, 2H).

[0352] 13C NMR (101 MHz, DMSO-D6) δ 161.47, 159.63, 143.42, 142.15, 136.00,135.70, 132.85, 130.79, 130.67, 129.76, 128.00, 123.94, 123.53, 114.84,111.55, 35.26.

[0353] Compound 77:

[0354]

[0355] 1H NMR (400 MHz, DMSO-D6) δ 12.63 (s, 1H), 9.28 (s, 1H), 7.85 (dt, J= 7.5, 2.0 Hz, 1H), 7.66 – 7.59 (m, 2H), 7.48 (dt, J = 7.5, 2.0 Hz, 1H), 7.06(s, 1H), 6.77 (s, 1H), 4.00 (s, 2H).

[0356] 13C NMR (101 MHz, DMSO-D6) δ 163.63, 159.63, 143.42, 142.15, 137.94,135.98, 133.68, 130.96, 130.46, 129.76, 123.94, 123.53, 120.40, 114.84,111.55, 35.26.

[0357] Compound 78:

[0358]

[0359] 1H NMR (400 MHz, DMSO-D6) δ 12.64 (s, 1H), 9.27 (s, 1H), 7.87 (dt, J= 7.5, 2.0 Hz, 2H), 7.64 (s, 2H), 7.57 (t, J = 7.5 Hz, 2H), 7.53 (t, J = 2.0Hz, 2H), 7.13 (dt, J = 7.5, 2.0 Hz, 2H), 7.06 (s, 2H), 6.77 (s, 1H), 4.00 (s,3H).

[0360] 13C NMR (101 MHz, DMSO-D6) δ 163.72, 163.07, 159.63, 143.42, 142.15,133.28, 133.05, 131.08, 129.76, 123.94, 123.53, 121.42, 115.47, 114.84,111.55, 35.26.

[0361] Compound 79:

[0362]

[0363] 1H NMR (400 MHz, DMSO-D6) δ 12.63 (s, 1H), 9.26 (s, 1H), 8.06 – 8.01(m, 1H), 7.66 – 7.51 (m, 5H), 7.06 (s, 1H), 6.77 (s, 1H), 4.00 (s, 2H).

[0364] 13C NMR (101 MHz, DMSO-D6) δ 161.95, 159.63, 143.42, 142.15, 136.25,134.83, 133.91, 130.02, 129.76, 126.46, 125.70, 125.27, 123.94, 123.53,114.84, 111.55, 35.26.

[0365] Compound 80:

[0366]

[0367] 1H NMR (400 MHz, DMSO-D6) δ 12.61 (s, 1H), 9.24 (s, 1H), 8.12 (t, J =1.6 Hz, 1H), 7.87 (ddd, J = 6.2, 3.2, 2.0 Hz, 1H), 7.72 – 7.62 (m, 3H), 7.06(s, 1H), 6.77 (s, 1H), 4.00 (s, 2H).

[0368] 13C NMR (101 MHz, DMSO-D6) δ163.49, 159.63, 143.42, 142.15, 133.88,131.28, 131.27, 130.95, 129.76, 127.20, 126.19, 123.94, 123.53, 114.84,111.55, 35.26.

[0369] Compound 81:

[0370]

[0371] 1H NMR (400 MHz, DMSO-D6) δ 12.74 (s, 1H), 9.33 (s, 1H), 8.05 – 7.99 (m, 2H), 7.72 – 7.66 (m, 2H), 7.64 (s, 1H), 7.06 (s, 1H), 6.77 (s, 1H), 4.00(s, 2H).

[0372] 13C NMR (101 MHz, DMSO-D6) δ 164.28, 159.63, 143.42, 142.15, 136.15,134.69, 130.08, 129.76, 127.26, 125.72, 123.94, 123.53, 114.84, 111.55,35.26.

[0373] Compound 82:

[0374]

[0375] 1H NMR (400 MHz, DMSO-D6) δ 12.64 (s, 1H), 9.26 (s, 1H), 7.79 (dd, J= 7.4, 1.7 Hz, 1H), 7.64 (s, 1H), 7.49 – 7.41 (m, 1H), 7.41 – 7.32 (m, 2H),7.06 (s, 1H), 6.77 (s, 1H), 4.00 (s, 2H), 2.52 (d, J = 0.8 Hz, 3H).

[0376] 13C NMR (101 MHz, DMSO-D6) δ 163.17, 159.63, 143.42, 142.15, 138.47,134.61, 131.65, 130.56, 130.02, 129.76, 128.32, 123.94, 123.53, 114.84,111.55, 35.26, 20.34.

[0377] Compound 83:

[0378]

[0379] 1H NMR (400 MHz, DMSO-D6) δ 12.65 (s, 1H), 9.24 (s, 1H), 7.76 (dt, J= 7.5, 2.0 Hz, 1H), 7.70 (tq, J = 2.0, 1.0 Hz, 1H), 7.64 (s, 1H), 7.42 (t, J= 7.5 Hz, 1H), 7.13 (dtt, J = 7.5, 2.0, 1.1 Hz, 1H), 7.06 (s, 1H), 6.77 (s,1H), 4.00 (s, 2H), 2.36 (d, J = 2.0 Hz, 2H).

[0380] 13C NMR (101 MHz, DMSO-D6) δ 164.04, 159.63, 143.42, 142.15, 137.23,135.89, 135.61, 131.45, 129.95, 129.84, 129.76, 123.94, 123.53, 114.84,111.55, 35.26, 23.16.

[0381] Compound 84:

[0382]

[0383] 1H NMR (400 MHz, DMSO-D6) δ 12.64 (s, 1H), 9.26 (s, 1H), 7.81 – 7.75 (m, 2H), 7.64 (s, 1H), 7.39 – 7.33 (m, 1H), 7.06 (s, 1H), 6.77 (s, 1H), 4.00(s, 1H), 2.36 (d, J = 2.0 Hz, 1H).

[0384] 13C NMR (101 MHz, DMSO-D6) δ 164.28, 159.63, 147.71, 143.42, 142.15,132.34, 131.62, 130.47, 129.76, 123.94, 123.53, 114.84, 111.55, 35.26, 22.80.

[0385] Compound 85:

[0386]

[0387] 1H NMR (400 MHz, DMSO-D6) δ 12.65 (s, 1H), 9.24 (s, 1H), 7.79 (dd, J= 7.5, 2.0 Hz, 1H), 7.64 (s, 1H), 7.41 (td, J = 7.5, 2.0 Hz, 1H), 7.23 (td, J= 7.5, 2.0 Hz, 1H), 7.09 – 7.03 (m, 1H), 6.77 (s, 1H), 4.00 (s, 1H), 3.86 (s, 2H).

[0388] 13C NMR (101 MHz, DMSO-D6) δ 162.49, 159.63, 157.94, 143.42, 142.15,133.14, 131.25, 129.76, 125.67, 124.03, 123.94, 123.53, 114.84, 114.08,111.55, 57.06, 35.26.

[0389] Compound 86:

[0390]

[0391] 1H NMR (400 MHz, DMSO-D6) δ 12.63 (s, 1H), 9.16 (s, 1H), 7.80 – 7.74 (m, 2H), 7.64 (s, 1H), 7.06 (s, 1H), 7.04 – 6.98 (m, 2H), 6.77 (s, 1H), 4.00(s, 2H), 3.79 (s, 2H).

[0392] 13C NMR (101 MHz, DMSO-D6) δ 164.96, 164.04, 159.63, 143.42, 142.15,131.04, 129.76, 129.70, 123.94, 123.53, 114.84, 114.69, 111.55, 55.86, 35.26.

[0393] Compound 87:

[0394]

[0395] 1H NMR (400 MHz, DMSO-D6) δ 12.61 (s, 1H), 9.26 (s, 1H), 7.81 – 7.75 (m, 2H), 7.64 (s, 1H), 7.40 – 7.33 (m, 2H), 7.06 (s, 1H), 6.77 (s, 1H), 4.00(s, 2H), 2.65 (t, J = 1.0 Hz, 2H), 1.22 (s, 2H).

[0396] 13C NMR (101 MHz, DMSO-D6) δ 164.28, 159.63, 149.06, 143.42, 142.15,132.80, 130.58, 129.76, 129.65, 123.94, 123.53, 114.84, 111.55, 35.26, 30.94,15.96.

[0397] Compound 88:

[0398]

[0399] 1H NMR (400 MHz, DMSO-D6) δ 12.63(s, 1H), 9.29 (s, 1H), 7.83 (d, J =2.0 Hz, 2H), 7.64 (s, 1H), 7.41 (t, J = 2.0 Hz, 1H), 7.06 (s, 1H), 6.77 (s,1H), 4.00 (s, 2H).

[0400] 13C NMR (101 MHz, DMSO-D6) δ 163.72, 159.63, 143.42, 142.15, 135.41,134.92, 133.91, 129.76, 127.47, 123.94, 123.53, 114.84, 111.55, 35.26.

[0401] Compound 89:

[0402]

[0403] 1H NMR (400 MHz, DMSO-D6) δ 12.61 (s, 1H), 9.26 (s, 1H), 7.64 (s,1H), 7.52 (d, J = 2.0 Hz, 2H), 7.06 (s, 1H), 6.88 (t, J = 1.9 Hz, 1H), 6.77(s, 1H), 4.00(s, 2H).

[0404] 13C NMR (101 MHz, DMSO-D6) δ 163.43, 163.12, 159.63, 143.42, 142.15,135.81, 129.76, 123.94, 123.53, 114.84, 113.43, 111.55, 110.04, 35.26.

[0405] Compound 90:

[0406]

[0407] 1H NMR (400 MHz, DMSO-D6) δ 12.64 (s, 1H), 9.26 (s, 1H), 7.96 (dd, J= 7.5, 2.0 Hz, 1H), 7.64 (s, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.06 (s, 1H),7.08 – 7.02 (m, 1H), 6.77 (s, 1H), 4.00 (s, 2H).

[0408] 13C NMR (101 MHz, DMSO-D6) δ 161.98, 159.63, 152.26, 152.00, 143.42,142.15, 129.76, 129.25, 128.64, 127.53, 123.94, 123.53, 120.75, 114.84,111.55, 35.26.

[0409] Example 2: Study on the biological activity of indomethacin derivatives against wheat aphids, spider mites, and armyworms.

[0410] (1) Experiment on the effect of indomethacin derivatives on wheat aphid activity

[0411] The inhibitory activity of the indomethacin derivatives listed in Table 1 against aphids was determined using the slide immersion method. Specific method: A certain amount of the test compound was accurately weighed and dissolved in acetone. A solution with a concentration of 100 μg / mL was prepared by adding 0.1% Tween-80 aqueous solution. The solution was allowed to stand at room temperature for half an hour until completely dissolved before storage. The aphids and branches were immersed in the prepared solution for 5 seconds, then removed and blotted dry with absorbent paper. Thiamethoxam was used as the positive control, and 0.1% Tween-80 aqueous solution was used as the negative control. After 48 hours of humidified culture in petri dishes, the mortality rate was observed. The results are shown in Table 1.

[0412] Table 1. Bioactivity of indomethacin derivatives against wheat aphids at 100 μg / mL

[0413] compound mortality rate(%) compound mortality rate(%) compound mortality rate(%) compound mortality rate(%) 1 45.87 24 48.73 47 49.19 70 48.95 2 12.38 25 39.85 48 35.81 71 37.70 3 23.12 26 45.21 49 47.65 72 46.54 4 27.58 27 27.89 50 13.11 73 12.11 5 41.35 28 41.38 51 40.87 74 42.73 6 48.19 29 38.96 52 32.99 75 34.97 7 32.64 30 12.71 53 48.56 76 49.10 8 47.83 31 21.28 54 13.12 77 22.59 9 19.45 32 43.71 55 44.29 78 45.21 10 43.28 33 29.49 56 31.85 79 17.81 11 10.16 34 47.83 57 46.97 80 47.91 12 48.91 35 36.60 58 15.73 81 24.65 13 28.54 36 42.95 59 43.61 82 44.80 14 46.17 37 25.76 60 23.88 83 16.39 15 39.88 38 48.17 61 47.30 84 48.37 16 58.72 39 20.07 62 38.16 85 36.76 17 67.45 40 46.74 63 45.91 86 46.19 18 78.91 41 21.58 64 20.77 87 18.98 19 85.36 42 44.90 65 43.00 88 13.17 20 15.39 43 37.43 66 16.52 89 39.54 21 71.43 44 68.54 67 72.48 90 88.72 22 88.76 45 79.82 68 81.65 Thiamethoxam 100.00 23 55.98 46 85.17 69 65.93

[0414] Table 1 shows the results of indoor bioassays, indicating that the tested compounds have good bioactivity against aphids, with some compounds causing a mortality rate of more than 80% in wheat aphids at a concentration of 100 μg / mL.

[0415] (2) Experiment on the effect of indomethacin derivatives on the activity of Tetranychus cinnabarinus

[0416] The bioactivity of the indothiazole derivatives listed in Table 2 against the spider mite was determined using the slide immersion method, the same method used for aphids. The results are shown in Table 2.

[0417] Table 2. Bioactivity of indomethacin derivatives against spider mites at 100 μg / mL

[0418] compound mortality rate(%) compound mortality rate(%) compound mortality rate(%) compound mortality rate(%) 1 20.81 24 21.04 47 13.08 70 32.15 2 39.92 25 17.42 48 29.74 71 47.69 3 79.84 26 51.46 49 41.36 72 12.57 4 26.35 27 67.23 50 55.89 73 73.51 5 59.24 28 33.86 51 32.17 74 28.46 6 30.39 29 86.61 52 76.42 75 51.37 7 59.66 30 97.16 53 69.05 76 82.60 8 71.12 31 74.57 54 23.81 77 36.94 9 52.27 32 56.54 55 81.63 78 64.21 10 64.12 33 65.81 56 47.29 79 22.78 11 66.58 34 20.25 57 10.03 80 59.33 12 45.92 35 84.48 58 52.74 81 18.30 13 15.12 36 70.06 59 21.51 82 78.14 14 57.85 37 75.82 60 72.18 83 42.67 15 57.88 38 59.19 61 44.62 84 31.85 16 28.54 39 25.29 62 27.51 85 69.22 17 74.79 40 25.37 63 61.83 86 25.91 18 58.19 41 14.59 64 39.07 87 85.37 19 76.15 42 88.40 65 85.26 88 18.21 20 71.69 43 44.47 66 58.44 89 15.06 21 67.13 44 86.61 67 31.79 90 81.02 22 64.16 45 28.66 68 17.77 Pyridaben 98.53 23 82.59 46 20.99 69 22.95

[0419] Table 2 shows that the results of indoor bioassays indicate that the tested compounds have good bioactivity against spider mites. Most of the tested compounds have certain bioactivity against spider mites, and compound (30) has a similar acaricidal effect to pyridaben.

[0420] (3) Experiment on the effect of indomethacin derivatives on the activity of *Armoria spp.*

[0421] The third instar larvae of the Eastern armyworm were used as test insects in a 24-hour starvation experiment. Chlorfenapyr was used as a positive control. The activity was determined using the leaf-dish method. In the initial screening stage, the test samples were prepared as 500 μg / mL / acetone solutions, and the control agent chlorfenapyr was prepared as a 100 μg / mL / acetone solution. Fresh wheat leaves were cut into 5 mm × 5 mm square pieces and immersed in the prepared solution for 5 s. Subsequently, after the acetone had evaporated, the leaf-dish pieces were added to the wells of a 24-well plate containing third instar larvae of the Eastern armyworm, one leaf-dish per well and one test insect per well. Each sample was tested in triplicate, with 12 test insects per group. Leaves treated with acetone served as blank controls. The number of live armyworms was recorded after 48 h, and the mortality rate was calculated. The results are shown in Table 3.

[0422] Table 3. Bioactivity of indomethacin derivatives against *Armoria spp.* at 100 μg / mL

[0423] compound mortality rate(%) compound mortality rate(%) compound mortality rate(%) compound mortality rate(%) 1 33.86 24 38.43 47 62.17 70 75.49 2 51.86 25 23.87 48 45.39 71 48.87 3 44.32 26 77.79 49 28.74 72 86.14 4 11.18 27 77.89 50 71.52 73 64.06 5 89.95 28 49.47 51 13.55 74 78.96 6 31.79 29 75.34 52 53.81 75 55.44 7 17.45 30 15.18 53 37.95 76 71.27 8 77.16 31 32.21 54 84.26 77 55.25 9 56.97 32 59.04 55 22.57 78 40.36 10 16.35 33 31.03 56 69.33 79 84.31 11 51.04 34 55.14 57 16.82 80 26.88 12 30.21 35 52.67 58 49.05 81 56.54 13 60.67 36 33.91 59 77.11 82 60.21 14 24.72 37 56.19 60 31.49 83 77.16 15 71.96 38 62.22 61 11.39 84 57.11 16 14.45 39 65.99 62 25.73 85 74.15 17 97.14 40 21.72 63 81.34 86 27.32 18 20.25 41 52.97 64 34.92 87 19.96 19 30.21 42 70.99 65 66.78 88 73.71 20 45.85 43 78.88 66 20.15 89 75.54 21 63.08 44 65.72 67 72.59 90 13.36 22 67.07 45 18.21 68 41.86 chlorfenapyr 99.35 23 72.03 46 50.37 69 17.45

[0424] Table 3 shows that the results of indoor bioassays indicate that the tested compounds have good activity against the Eastern armyworm, and compound (17) has a similar insecticidal effect to chlorfenapyr.

[0425] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, are covered within the scope of protection of the present invention.

Claims

1. An indothiazole derivative, characterized in that, The derivative has a chemical structure as described in formula (I), formula (II), or formula (III): Wherein, R is any one of alkyl, phenyl, substituted phenyl or heterocyclic, and the alkyl is an aliphatic chain or cycloalkanes.

2. The indothiazole derivative according to claim 1, characterized in that, The chemical structural formula of the derivative is any one of 1 to 90: 。 In the formula, (2) to (8) represent the number of carbons at the position on the carbon chain of the derivative.

3. The method for synthesizing the indothiazole derivative according to claim 1, characterized in that, The synthetic route is as follows: 。 4. The method for synthesizing the indothiazole derivative according to claim 3, characterized in that, Step a specifically involves dissolving compound (A) in a mixed solvent of dichloromethane and ethyl acetate, adding copper bromide, and reacting at 70–80°C for 10–14 h to generate compound (B). Step b is as follows: Compound (B) is dissolved in dichloromethane, tert-butyldimethylchlorosilane and imidazole are added, and the mixture is reacted at 0°C for 8 to 12 min and then at room temperature for 2 to 4 h to generate compound (C). Step c specifically involves dissolving compound (C) in anhydrous ethanol, adding thiourea, and reacting at 85–95°C for 10–14 h to generate compound (D).

5. The method for synthesizing the indothiazole derivative according to claim 3, characterized in that, Step d specifically involves dissolving compound (D) in anhydrous dichloromethane, then adding triethylamine, 4-dimethylaminopyridine, and acyl chloride sequentially, reacting at 0°C for 8–12 min, and then reacting at room temperature for 5–7 h to generate compound (E). Step e specifically involves dissolving compound (D) in acetonitrile, then adding triethylamine, 4-dimethylaminopyridine, and sulfonyl chloride sequentially, reacting at 0°C for 10 min, and then reacting at room temperature for 5–7 h to generate compound (F). Step f specifically involves dissolving compound (D) in acetone, adding potassium carbonate and benzyl bromide, and reacting at 70–80°C for 10–14 h to generate compound (G).

6. The method for synthesizing the indothiazole derivative according to claim 3, characterized in that, Step g specifically involves dissolving compounds (E), (G), and (F) in tetrahydrofuran, adding tetrabutylammonium fluoride, and reacting at room temperature for 25–35 min to generate compounds (I), (II), or (III), respectively.

7. The application of the indothiazole derivative as described in claim 1 or 2, or the indothiazole derivative synthesized by the method described in any one of claims 4-6, in the control of plant pests.

8. The application according to claim 7, characterized in that, The plant pests mentioned are aphids, spider mites, and oriental armyworms.

9. An insecticide, characterized in that, It includes the indothiazole derivative as described in claim 1 or 2.

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