CN115677586B - Polysubstituted aminopyrazole compound and preparation method and application thereof - Google Patents
Polysubstituted aminopyrazole compound and preparation method and application thereof Download PDFInfo
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- -1 Polysubstituted aminopyrazole compound Chemical class 0.000 title claims abstract description 64
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 150000001875 compounds Chemical class 0.000 claims description 54
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 claims description 6
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- 201000011510 cancer Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 32
- 239000003054 catalyst Substances 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 8
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- 150000003217 pyrazoles Chemical class 0.000 abstract description 6
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- 238000011161 development Methods 0.000 abstract description 5
- 125000004185 ester group Chemical group 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
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- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 238000010490 three component reaction Methods 0.000 abstract description 3
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 abstract 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 238000004611 spectroscopical analysis Methods 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 125000004076 pyridyl group Chemical group 0.000 description 16
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- 239000003960 organic solvent Substances 0.000 description 12
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 11
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- 230000015572 biosynthetic process Effects 0.000 description 7
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- 229910052740 iodine Inorganic materials 0.000 description 7
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
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- 239000003480 eluent Substances 0.000 description 4
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 4
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- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 3
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
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- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
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- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 2
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- 230000035484 reaction time Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- KRIWIRSMQRQYJG-DLBZAZTESA-N (2s,3s)-3-[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]butane-1,2,4-triol Chemical compound C=1C(N[C@@H](CO)[C@H](O)CO)=NC2=C(C(C)C)C=NN2C=1NCC1=CC=CC=C1 KRIWIRSMQRQYJG-DLBZAZTESA-N 0.000 description 1
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- QOLHWXNSCZGWHK-BWBORTOCSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecylcarbamoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)NCCCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 QOLHWXNSCZGWHK-BWBORTOCSA-N 0.000 description 1
- CXIJSTYYDYSTCX-UHFFFAOYSA-N 1-isothiocyanato-4-methoxy-2-methylbenzene Chemical compound COC1=CC=C(N=C=S)C(C)=C1 CXIJSTYYDYSTCX-UHFFFAOYSA-N 0.000 description 1
- VRPQCVLBOZOYCG-UHFFFAOYSA-N 1-isothiocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=S)C=C1 VRPQCVLBOZOYCG-UHFFFAOYSA-N 0.000 description 1
- YLLRPQWLASQXSI-UHFFFAOYSA-N 3-(4b,8a,9,9a-tetrahydro-4aH-pyrido[2,3-b]indol-4-ylamino)phenol Chemical compound Oc1cccc(NC2=CC=NC3NC4C=CC=CC4C23)c1 YLLRPQWLASQXSI-UHFFFAOYSA-N 0.000 description 1
- LIDUGWDLSDKCLM-CSKARUKUSA-N 4-[[3-[[[(e)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]benzonitrile Chemical compound CC(C)(C)C#C/C=C/CN(CC)CC1=CC=CC(OC[Si](C)(C)C=2C=CC(=CC=2)C#N)=C1 LIDUGWDLSDKCLM-CSKARUKUSA-N 0.000 description 1
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- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
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- CDVMXMZPDJHSCC-UHFFFAOYSA-N chembl1684662 Chemical compound C=1C=C2C=C(C=3C4=NC=CC=C4NN=3)NC2=CC=1CC(=O)C1=CC=CC=C1 CDVMXMZPDJHSCC-UHFFFAOYSA-N 0.000 description 1
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- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a polysubstituted aminopyrazole compound, and a preparation method and application thereof. The polysubstituted aminopyrazole compound of the invention contains amino, ester group or amido bond, secondary amine and other active sites of polyfunctional groups, which is favorable for further organic conversion reaction and development of heterocyclic pyrazole compounds with anticancer, anti-inflammatory, bactericidal and other activities; the preparation method of the polysubstituted aminopyrazole compound realizes the convenient construction of arylamino pyrazole heterocyclic skeleton molecules by three components under a green solvent system with the simplest substrate, and simultaneously has the advantages of cheap and easily obtained raw materials, high safety of used catalyst and solvent, simple operation of one-pot three-component reaction, good reaction selectivity, high yield, good atomic economy and easy separation of products compared with the existing method for synthesizing polysubstituted pyrazole after optimizing the reaction conditions.
Description
Technical Field
The invention relates to the technical field of organic medicine synthesis, in particular to a polysubstituted aminopyrazole compound, and a preparation method and application thereof.
Background
Natural products, particularly heterocyclic compounds, have become an important source of potential drug molecule design and drug molecule library construction. Through strengthening the optimization design research on natural product molecules, the novel structure of the high-activity molecules can be found, and the physical and chemical properties of parent molecules can be improved; meanwhile, the synthesis design based on natural products promotes the research of new theory, new reaction and new method, thereby realizing the efficient preparation and industrialized development of drug molecules.
Heterocyclic pyrazoles containing N-N bonds are widely present in a plurality of natural products and synthetic drug molecules with excellent biological activity, and often have various pharmacological and pesticide activities such as pain relieving, anti-inflammatory, antibacterial, anti-tumor, blood sugar regulating, anticoagulation, disinsection, sterilization and the like. Many of these compounds have been successfully developed as commercial drugs, such as Celecoxib (Celecoxib), lei Zasha shift Rezaxaban, and other clinical drugs.
Heterocyclic pyrazoles are important molecular frameworks with excellent activity, but traditional synthesis methods inevitably need to use complex substrates to construct pyrazole rings, or longer synthesis steps to modify pyrazole rings, or use organic reagents with high toxicity and high danger, and sometimes use metal organic reagents and the like, so how to simply and efficiently construct polysubstituted pyrazole molecules has been the focus of research in the field of synthetic chemistry.
The synthesis of polysubstituted pyrazoles by the existing method has a plurality of problems, especially the introduction of ester group and amino difunctional groups into the pyrazole heterocyclic system simultaneously, usually requires the synthesis of a substrate with a special structure, and then adopts a ring closing reaction strategy to realize the synthesis of the pyrazole ring, or after the construction of the pyrazole ring, the nitration reaction, the halogenation reaction and the like are adopted to introduce functional groups with certain reactivity respectively, which increase the complexity and uncontrollability of the reaction. Meanwhile, the polysubstituted pyrazole compound synthesized at present has insufficient activity, which is not beneficial to further organic transformation reaction to develop heterocyclic pyrazole compound with anticancer, anti-inflammatory, bactericidal and other activities.
There is a need for improvements in the art based on the current synthesis of polysubstituted pyrazoles.
Disclosure of Invention
In view of the above, the invention provides a polysubstituted aminopyrazole compound, and a preparation method and application thereof, so as to solve or at least partially solve the technical problems existing in the prior art.
In a first aspect, the present invention provides a polysubstituted aminopyrazole compound having the structural formula:
Wherein R 1 is any one of pyridinyl, substituted pyridinyl, alkoxy, alkyl, oxazolyl, isoxazolyl, naphthyl, thienyl, furanyl, quinolinyl, phenyl, or substituted phenyl; the substituent groups on the substituted phenyl and the substituted pyridyl are one, two or three of alkoxy, alkyl, trifluoromethyl, halogen, nitro, carboxyl, acetyl, cyano and trifluoromethoxy;
r 2 is any one of alkyl, phenyl, substituted phenyl, pyridyl, substituted pyridyl, thienyl and trifluoromethyl;
R 3 is any one of alkoxy, alkenyloxy, phenoxy, amino and substituted amino.
Preferably, the polysubstituted aminopyrazole compound, wherein R 1 is any one of pyridyl, substituted pyridyl, phenyl or substituted phenyl;
R 2 is any one of substituted phenyl, substituted pyridyl, thienyl and trifluoromethyl;
R 3 is any one of alkoxy, alkenyloxy, phenoxy, amino and substituted amino.
In a second aspect, the invention also provides a preparation method of the polysubstituted aminopyrazole compound, which comprises the following steps:
Adding hydrazine hydrate, R 1 substituted isothiocyanate and R 2、R3 substituted 1, 3-dicarbonyl compound into an organic solvent, then adding a catalyst, and reacting to obtain the polysubstituted aminopyrazole compound.
Preferably, the preparation method of the polysubstituted aminopyrazole compound has the reaction temperature of 0-100 ℃ and the reaction time of 4-6 h.
Preferably, the organic solvent comprises at least one of 1, 4-dioxane, acetonitrile, tetrahydrofuran and ethanol dichloromethane.
Preferably, the preparation method of the polysubstituted aminopyrazole compound comprises the step of preparing the polysubstituted aminopyrazole compound by using a Lewis acid catalyst.
Preferably, in the preparation method of the polysubstituted aminopyrazole compound, the Lewis acid catalyst is elemental iodine.
Preferably, the molar ratio of hydrazine hydrate, R 1 substituted isothiocyanate and R 2、R3 substituted 1, 3-dicarbonyl compound is (0.5-1);
The molar ratio of the R 1 substituted isothiocyanate to the catalyst is (1-2) to (1-2).
Preferably, in the preparation method of the polysubstituted aminopyrazole compound, the molar volume ratio of the R 1 substituted isothiocyanate to the organic solvent is (0.5-1) mmol (3-6) mL.
In a third aspect, the invention also provides an application of the polysubstituted aminopyrazole compound or the polysubstituted aminopyrazole compound prepared by the preparation method in preparation of anticancer drugs, anti-inflammatory drugs and bactericidal drugs.
The polysubstituted aminopyrazole compound, the preparation method and the application thereof have the following beneficial effects compared with the prior art:
1. the polysubstituted aminopyrazole compound of the invention contains amino, ester group or amido bond, secondary amine and other active sites of polyfunctional groups, which is favorable for further organic conversion reaction and development of heterocyclic pyrazole compounds with anticancer, anti-inflammatory, bactericidal and other activities;
2. The preparation method of the polysubstituted aminopyrazole compound realizes the convenient construction of arylamino pyrazole heterocyclic skeleton molecules by three components under a green solvent system with the simplest substrate, and simultaneously has the advantages of cheap and easily obtained raw materials, high safety of used catalyst and solvent, simple operation of one-pot three-component reaction, good reaction selectivity, high yield, good atomic economy and easy separation of products compared with the existing method for synthesizing polysubstituted pyrazole after optimizing the reaction conditions.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. It will be apparent that the described embodiments are some, but not all, embodiments of the invention.
The following description of the embodiments of the present invention will be made in detail and with reference to the embodiments of the present invention, but it should be apparent that the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, are intended to fall within the scope of the present invention.
For a better understanding of the present application, and not to limit its scope, all numbers expressing quantities, percentages, and other values used in the present application are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated otherwise, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained. Each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.
The embodiment of the application provides a polysubstituted aminopyrazole compound, which has the structural formula:
Wherein R 1 is any one of pyridinyl, substituted pyridinyl, alkoxy, alkyl, oxazolyl, isoxazolyl, naphthyl, thienyl, furanyl, quinolinyl, phenyl, or substituted phenyl; the substituent groups on the substituted phenyl and the substituted pyridyl are one, two or three of alkoxy, alkyl, trifluoromethyl, halogen, nitro, carboxyl, acetyl, cyano and trifluoromethoxy;
r 2 is any one of alkyl, phenyl, substituted phenyl, pyridyl, substituted pyridyl, thienyl and trifluoromethyl;
R 3 is any one of alkoxy, alkenyloxy, phenoxy, amino and substituted amino.
In some embodiments, R 1 is any one of pyridinyl, substituted pyridinyl, phenyl, or substituted phenyl;
R 2 is any one of substituted phenyl, substituted pyridyl, thienyl and trifluoromethyl;
R 3 is any one of alkoxy, alkenyloxy, phenoxy, amino and substituted amino.
The polysubstituted aminopyrazole compound of the application contains amino, ester group or amido bond, secondary amine and other active sites of polyfunctional groups, which is favorable for further organic transformation reaction and development of heterocyclic pyrazole compounds with anticancer, anti-inflammatory, bactericidal and other activities.
Based on the same inventive concept, the embodiment of the application also provides a preparation method of the polysubstituted aminopyrazole compound, which comprises the following steps:
Adding hydrazine hydrate, R 1 substituted isothiocyanate and R 2、R3 substituted 1, 3-dicarbonyl compound into an organic solvent, then adding a catalyst, and reacting to obtain the polysubstituted aminopyrazole compound.
Specifically, the reaction principle of the preparation method of the application is as follows:
In some embodiments, the reaction temperature is from 0 to 100 ℃ and the reaction time is from 4 to 6 hours.
In some embodiments, the organic solvent comprises at least one of 1, 4-dioxane, acetonitrile, tetrahydrofuran, ethanol dichloromethane.
In some embodiments, the catalyst is a lewis acid catalyst.
In some embodiments, the lewis acid catalyst is elemental iodine.
In some embodiments, the molar ratio of hydrazine hydrate, R 1 substituted isothiocyanate, R 2、R3 substituted 1, 3-dicarbonyl compound is (0.5-1): 0.5-1;
The molar ratio of R 1 substituted isothiocyanate to the catalyst is (1-2).
In some embodiments, the molar volume ratio of R 1 substituted isothiocyanate to the organic solvent is (0.5-1) mol (3-6) mL.
In some embodiments, hydrazine hydrate, R 1 substituted isothiocyanate and R 2、R3 substituted 1, 3-dicarbonyl compound are added into an organic solvent, then a catalyst is added, a crude product of the polysubstituted aminopyrazole compound is obtained through reaction, and the crude product of the polysubstituted aminopyrazole compound is separated through silica gel column chromatography; wherein the eluent of the silica gel column chromatography is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is (5-20): 1.
Compared with other synthesis methods existing before, the polysubstituted aminopyrazole synthesized by the invention contains amino, ester group or amido bond, secondary amine and other multifunctional active sites, which is favorable for further organic transformation reaction and development of heterocyclic pyrazole compounds with anticancer, anti-inflammatory, bactericidal and other activities. Meanwhile, the preparation method has the advantages of cheap and easily available raw materials, high safety of the used catalyst and solvent, simple operation of one-pot three-component reaction, good reaction selectivity, high yield, good atomic economy and easy separation of products after optimizing the reaction conditions, and has remarkable advantages compared with the existing method for synthesizing the polysubstituted pyrazole.
Based on the same inventive concept, the embodiment of the application also provides an application of the polysubstituted aminopyrazole compound or the polysubstituted aminopyrazole compound prepared by the preparation method in preparation of anticancer drugs, anti-inflammatory drugs and bactericidal drugs.
The preparation method and application of the Fenton-like catalyst of the present application are further described in the following specific examples. This section further illustrates the summary of the application in connection with specific embodiments, but should not be construed as limiting the application. The technical means employed in the examples are conventional means well known to those skilled in the art, unless specifically stated. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present application are those conventional in the art.
Example 1
The embodiment of the application provides a partial polysubstituted aminopyrazole compound, the structural formula (the numbers and letters below the structural formula are compound numbers) of which is shown as follows:
Example 2
The compound numbered 4a in example 1 was prepared according to the following reaction scheme:
specifically, the preparation method of the compound 4a comprises the following steps: dissolving 0.5mmol of hydrazine hydrate, 0.5mmol of phenyl isothiocyanate and 0.5mmol of ethyl acetoacetate in 3mL of organic solvent ethanol respectively, and adding 0.5mmol of catalyst elemental iodine to obtain a reaction solution; the reaction solution was stirred in a reactor equipped with magnetic stirring at 60℃for 6 hours. After the reaction, the mixture was concentrated under reduced pressure, followed by silica gel column chromatography (V Petroleum ether ：V Acetic acid ethyl ester =20:1) and purification to give the product compound 4a (87.5 mg), yield 71% isolated. The spectrum data of the obtained compound 4a are as follows ：1H NMR(600MHz,CDCl3,25℃)δ＝8.24(s,1H),7.50–7.46(m,2H),7.28(dd,J＝8.6,7.3Hz,2H),6.94–6.90(m,1H),4.33(q,J＝7.1Hz,2H),2.41(s,3H),1.38(t,J＝7.2Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.50,153.79,143.98,141.07,129.10,120.81,117.24,96.90,59.96,14.44,12.35ppm.
Example 3
The compound numbered 4b in example 1 was prepared according to the following reaction scheme:
Specifically, the preparation method of the compound 4b comprises the following steps: dissolving 0.5mmol of hydrazine hydrate, 0.5mmol of 2-chloro-5-pyridine isothiocyanate and 0.5mmol of ethyl acetoacetate in 3mL of organic solvent ethanol respectively, and adding 0.5mmol of catalyst elemental iodine to obtain a reaction solution; the reaction mixture was stirred in a reactor equipped with magnetic stirring at 60℃for 6 hours. After the completion of the reaction, the mixture was concentrated under reduced pressure, followed by silica gel column chromatography (V Petroleum ether ：V Acetic acid ethyl ester =20:1) to obtain 112.5mg of compound 4b, which was isolated in 73% yield. The spectrum data of the obtained compound 4b are as follows ：1H NMR(600MHz,CDCl3,25℃)δ＝9.31(d,J＝3.0Hz,1H),8.41(s,1H),7.64(dd,J＝8.6,2.8Hz,1H),7.23(d,J＝8.6Hz,1H),4.35(q,J＝7.1Hz,2H),2.56(s,3H),1.40(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.65,153.08,143.35,140.74,137.95,137.51,127.09,124.01,97.14,60.16,14.43,12.23ppm.
Example 4
The compound numbered 4c in example 1 was prepared according to the following reaction scheme:
Specifically, the preparation method of the compound 4c comprises the following steps: dissolving 0.5mmol of hydrazine hydrate, 0.5mmol of 4-methoxyphenyl isothiocyanate and 0.5mmol of ethyl acetoacetate in 3mL of organic solvent ethanol respectively, and adding 0.5mmo of catalyst elemental iodine to obtain a reaction solution; the reaction mixture was stirred in a reactor equipped with magnetic stirring at 60℃for 6 hours. After the reaction, the mixture was concentrated under reduced pressure, and subjected to silica gel column chromatography (eluent is a mixture of petroleum ether and ethyl acetate, the volume ratio of petroleum ether to ethyl acetate is 20:1), whereby compound 4c was obtained by purification in an amount of 107.0mg, and the isolation yield was 73%. The spectrum data of the obtained compound 4c are as follows ：1H NMR(600MHz,CDCl3,25℃)δ＝8.00(s,1H),7.44–7.32(m,2H),6.88–6.79(m,2H),4.32(q,J＝7.2Hz,2H),3.77(s,3H),2.38(s,3H),1.38(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.52,154.49,153.99,144.50,134.38,119.51,114.49,96.17,59.81,55.60,14.44,12.51ppm.
Example 5
The compound numbered 4ca in example 1 was prepared according to the following reaction scheme:
specifically, the preparation method of the compound 4ca comprises the following steps: dissolving 0.5mmol of hydrazine hydrate, 0.5mmol of 1-isothiocyanate-4-methoxy-2-toluene and 0.5mmol of (2-chlorobenzoyl) ethyl acetate in 3mL of organic solvent ethanol respectively, and adding 0.5mmol of catalyst elemental iodine to obtain a reaction solution; the reaction mixture was stirred in a reactor equipped with magnetic stirring at 60℃for 6 hours. After the reaction, the mixture was concentrated under reduced pressure, and subjected to silica gel column chromatography (eluent is a mixture of petroleum ether and ethyl acetate, the volume ratio of petroleum ether to ethyl acetate is 20:1), to obtain compound 4ca (113 mg), and the isolation yield was 61%. The spectrum data of the obtained compound 4ca are as follows ：1H NMR(600MHz,DMSO-d6,25℃)δ＝12.94(s,1H),8.11(s,1H),7.61–7.44(m,5H),6.90(d,J＝8.4Hz,2H),4.04(q,J＝7.0Hz,2H),3.73(s,3H),0.96(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝164.61,153.69,153.54,142.05,135.43,133.60,132.27,131.45,130.61,129.58,127.24,118.21,114.62,97.31,59.77,55.64,14.07ppm.
Example 6
The compound numbered 4d in example 1 was prepared according to the following reaction scheme:
specifically, the preparation method of the compound 4d comprises the following steps: dissolving 0.5mmol of hydrazine hydrate, 0.5mmol of 4-methoxy-2-methylphenyl isothiocyanate and 0.5mmol of ethyl acetoacetate in 3mL of organic solvent ethanol respectively, and adding 0.5mmol of catalyst elemental iodine to obtain a reaction solution; the reaction mixture was stirred in a reactor equipped with magnetic stirring at 60℃for 6 hours. After the reaction, the mixture is concentrated under reduced pressure, and silica gel column chromatography is carried out (the eluent is a mixture of petroleum ether and ethyl acetate, the volume ratio of petroleum ether to ethyl acetate is 20:1), and the compound 4d is obtained by purification, wherein the separation yield is 60%. The spectrum data of the obtained compound 4d are as follows ：1H NMR(600MHz,CDCl3,25℃)δ＝7.79(s,1H),7.66(d,J＝8.8Hz,1H),6.68(d,J＝3.0Hz,1H),6.63(dd,J＝8.8,3.0Hz,1H),4.25(q,J＝7.1Hz,2H),3.68(s,3H),2.28(s,3H),2.23(s,3H),1.30(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.67,154.74,153.94,145.10,132.44,129.00,120.21,116.40,111.46,95.88,59.81,55.51,18.17,14.53,12.70ppm.
Example 7
Referring to the basic synthesis methods described in examples 2-6, and combining the structural features of the compounds 4cb-4z listed in example 1, different conventional chemical raw materials are respectively selected, and other aminopyrazole compounds containing different substituents such as the compounds 4cb-4z can be prepared and subjected to corresponding analysis and test. The spectrum data of the above compound 4cb-4z are as follows:
Spectroscopic data for Compound 4cb ：1H NMR(600MHz,CDCl3,25℃)δ＝8.23(s,1H),7.57–7.52(m,2H),7.47–7.37(m,5H),6.86–6.81(m,2H),4.22(q,J＝7.1Hz,2H),3.78(s,3H),1.18(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.16,154.62,154.37,147.04,134.06,129.76,129.45,129.25,128.08,119.79,114.51,95.41,60.03,55.61,14.03ppm.
Spectroscopic data for Compound 4e ：1H NMR(600MHz,MeOH-d4,25℃)δ＝7.67(d,J＝8.2Hz,2H),7.53(d,J＝8.4Hz,2H),4.35(q,J＝7.1Hz,2H),2.47(s,3H),1.39(t,J＝7.0Hz,3H)ppm.13C NMR(151MHz,MeOH-d4,25℃)δ＝165.49,152.96,144.68,143.40,125.73,123.95,121.06(q,J＝32.5Hz),115.78,96.61,59.70,13.34,10.51ppm.19F NMR(565MHz,MeOH-d4,25℃)δ＝62.89ppm.
Spectroscopic data of Compound 4ea ：1H NMR(600MHz,CDCl3,25℃)δ＝8.61(d,J＝2.7Hz,1H),7.58–7.53(m,2H),7.48(m,1H),7.44–7.39(m,3H),7.37(m,1H),7.31(m,1H),4.15–4.09(tq,J＝7.1,1.2Hz,2H),1.03(tt,J＝7.1,1.2Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝164.83,153.03,143.73,142.77,134.06,131.52,131.07,129.63,128.49,126.48,126.32(p,J＝3.5Hz),124.60(q,J＝270.8Hz),122.17(q,J＝32.4Hz),116.38(p,J＝2.6Hz),98.68,60.24,13.66ppm.19F NMR(565MHz,CDCl3,25℃)δ＝61.42ppm.
Spectroscopic data for Compound 4eb ：1H NMR(600MHz,DMSO-d6,25℃)δ＝13.11(s,1H),8.79(s,1H),7.81(d,J＝8.4Hz,2H),7.66–7.58(m,4H),7.54–7.45(m,3H),4.18(q,J＝7.1Hz,2H),1.13(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝164.68,153.02,145.45,145.27,129.94,129.90,129.12,128.44,126.64(d,J＝4.1Hz),125.32(q,J＝270.4Hz),120.07(q,J＝32.0Hz),116.62,96.51,60.25,14.26ppm.19F NMR(565MHz,DMSO-d6,25℃)δ＝59.59ppm.
Spectroscopic data for Compound 4ec ：1H NMR(600MHz,CDCl3,25℃)δ＝8.53(s,1H),7.53–7.48(m,5H),4.20(q,J＝7.1Hz,2H),1.14(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝163.87,153.24(d,J＝262.6Hz),152.37,143.52(d,J＝3.4Hz),142.94,139.73,138.85(d,J＝20.9Hz),128.69(d,J＝21.4Hz),126.59(q,J＝3.8Hz),124.34(q,J＝270.9Hz),123.29(q,J＝32.6Hz),116.76,116.76,98.45,60.83,13.90ppm.19F NMR(565MHz,CDCl3,25℃)δ＝121.35ppm.
Spectroscopic data for Compound 4f ：1H NMR(600MHz,CDCl3,25℃)δ＝8.23(s,1H),8.03(d,J＝8.3Hz,1H),7.19–7.14(m,2H),6.87(t,J＝7.4Hz,1H),4.38–4.31(m,2H),2.38(s,3H),2.35(s,3H),1.38(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.65,153.60,144.23,139.36,130.37,126.87,125.16,120.89,116.74,96.87,59.99,17.93,14.52,12.35ppm.
Spectroscopic data for Compound 4g ：1H NMR(600MHz,CDCl3,25℃)δ＝7.44–7.38(m,2H),7.02–6.96(m,2H),4.33(qd,J＝7.1,3.5Hz,2H),2.43(d,J＝2.0Hz,3H),1.39(td,J＝7.1,3.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.63,157.51(d,J＝239.2Hz),153.66,144.10,137.01,137.00,118.76,118.70,115.53,115.38,96.30,59.94,14.31,12.03ppm.19F NMR(565MHz,CDCl3,25℃)δ＝120.37ppm.
Spectroscopic data for Compound 4ga ：1H NMR(600MHz,CDCl3,25℃)δ＝13.11(s,1H),8.79(s,1H),7.81(d,J＝8.4Hz,2H),7.66–7.58(m,4H),7.54–7.45(m,3H),4.18(q,J＝7.1Hz,2H),1.13(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝164.90,157.62(d,J＝239.5Hz),153.36,143.55,136.84,134.09,131.48,130.71,129.48,129.22,126.36,118.95(d,J＝7.5Hz),115.59(d,J＝22.6Hz),97.68,59.99,13.70ppm.19F NMR(565MHz,CDCl3,25℃)δ＝122.62ppm.
Spectroscopic data for Compound 4gb ：1H NMR(600MHz,CDCl3,25℃)δ＝8.38(s,1H),7.54(d,J＝7.3Hz,2H),7.66–7.58(m,5H),6.95(t,J＝8.3Hz,2H),4.22(q,J＝7.1Hz,2H),1.18(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.09,157.61(d,J＝239.6Hz),154.33,146.33,137.00,129.75,129.23,129.07,128.21,128.20,118.93(d,J＝7.8Hz),115.60(d,J＝22.5Hz),96.09,60.17,13.98ppm.19F NMR(565MHz,CDCl3,25℃)δ＝61.42ppm.
Spectroscopic data for Compound 4gc ：1H NMR(600MHz,DMSO-d6,25℃)δ＝13.26(s,1H),8.48(d,J＝8.1Hz,1H),8.23(s,1H),7.73–7.62(m,2H),7.13(t,J＝8.8Hz,2H),4.11(q,J＝7.1Hz,2H),1.03(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝163.84,157.60,156.03,153.38,152.66,143.62,138.21,138.09,137.43,137.29,131.03,130.89,127.44,122.09,118.51,118.46,116.55,115.83,115.69,98.16,60.28,14.14ppm.19F NMR(565MHz,DMSO-d6,25℃)δ＝120.32ppm.
Spectroscopic data for Compound 4h ：1H NMR(600MHz,CDCl3,25℃)δ＝9.00(s,1H),8.03(d,J＝7.4Hz,1H),8.00(d,J＝8.4Hz,1H),7.76(dd,J＝8.0,1.3Hz,1H),7.48–7.44(m,1H),7.44–7.38(m,2H),7.34(t,J＝7.8Hz,1H),4.33(q,J＝7.1Hz,2H),2.38(s,3H),1.36(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.74,153.70,144.49,135.89,134.29,128.65,126.20,125.88,125.83,124.94,121.61,120.57,113.04,97.12,60.18,14.51,12.55ppm.
Spectroscopic data for Compound 4i ：1H NMR(600MHz,DMSO-d6,25℃)δ＝12.79(s,1H),8.92(s,1H),8.20–8.12(m,2H),7.77–7.72(m,2H),4.27(q,J＝7.1Hz,2H),2.43(s,3H),1.31(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝164.70,151.51,148.16,143.75,139.55,126.00,125.91,117.01,116.12,97.93,60.18,14.66,11.97ppm.
Spectral data for Compound 4j ：1H NMR(600MHz,DMSO-d6,25℃)δ＝12.56(s,1H),8.30(s,1H),7.57(d,J＝8.4Hz,2H),7.40(d,J＝8.9Hz,2H),4.26(q,J＝7.1Hz,2H),2.40(s,3H),1.31(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝165.10,152.81,143.08,141.15,131.84,118.63,111.08,96.44,59.95,14.61,11.90ppm.
Spectroscopic data for Compound 4k ：1H NMR(600MHz,MeOH-d4,25℃)δ＝7.51–7.47(m,2H),7.23–7.20(m,2H),4.32(q,J＝7.1Hz,2H),2.45(s,3H),1.37(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,MeOH-d4,25℃)δ＝165.54,153.43,143.50,140.25,128.32,124.40,117.70,96.15,59.60,13.35,10.56ppm.
Spectroscopic data for Compound 4l ：1H NMR(600MHz,CDCl3,25℃)δ＝8.22(s,1H),7.29–7.26(m,2H),7.15(t,J＝8.1Hz,1H),6.73(d,J＝7.5Hz,1H),4.32(q,J＝7.1Hz,2H),2.32(s,3H),2.28(s,3H),1.38(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.56,153.70,144.13,140.97,138.96,128.95,121.72,117.90,114.34,96.66,59.93,21.59,14.45,12.23ppm.
Spectroscopic data for Compound 4m ：1H NMR(600MHz,CDCl3,25℃)δ＝8.14(s,1H),7.38–7.32(m,2H),7.13–7.05(m,2H),4.33(q,J＝7.1Hz,2H),2.47–2.38(m,3H),2.29(s,3H),1.39(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.49,153.72,144.24,138.37,130.45,129.64,117.59,96.49,59.92,20.71,14.46,12.57ppm.
Spectroscopic data for Compound 4n ：1H NMR(600MHz,CDCl3,25℃)δ＝8.18(s,1H),7.46–7.33(m,7H),7.26(dd,J＝8.6,7.3Hz,2H),6.91(td,J＝7.2,1.1Hz,1H),5.33(s,2H),2.41(s,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.05,153.74,144.14,140.97,136.14,129.09,128.70,128.29,128.03,120.90,117.28,96.67,65.81,12.50ppm.
Spectroscopic data for Compound 4o ：1H NMR(600MHz,CDCl3,25℃)δ＝8.21(s,1H),7.49–7.46(m,2H),7.27(t,J＝7.8Hz,2H),6.92(t,J＝7.4Hz,1H),3.86(s,3H),2.36(s,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.89,153.73,144.01,141.05,128.73,120.89,117.33,96.68,51.07,12.26ppm.
Spectroscopic data for Compound 4p ：1H NMR(600MHz,MeOH-d4,25℃)δ＝7.41–7.35(m,2H),7.19(t,J＝7.9Hz,2H),7.15–7.09(m,4H),7.01–6.96(m,1H),6.75(dq,J＝5.8,2.9Hz,1H),2.47(s,3H)ppm.13C NMR(151MHz,MeOH-d4,25℃)δ＝163.85,151.31,142.97,142.10,138.09,128.74,128.42,123.83,120.45,120.03,115.97,102.71,10.44ppm.
Spectroscopic data for Compound 4q ：1H NMR(600MHz,CDCl3,25℃)δ＝8.23(s,1H),7.47(d,J＝8.0Hz,2H),7.29–7.25(m,2H),6.91(t,J＝7.4Hz,1H),6.06–5.97(m,1H),5.38(dd,J＝17.2,1.6Hz,1H),5.28(dd,J＝10.4,1.5Hz,1H),4.78(dd,J＝5.6,1.6Hz,2H),2.33(s,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.17,153.80,144.13,140.99,132.41,129.12,120.92,118.09,117.27,96.53,64.60,12.31ppm.
Spectroscopic data for Compound 4r ：1H NMR(600MHz,CDCl3,25℃)δ＝8.18(s,1H),7.43–7.39(m,2H),7.23–7.18(m,2H),6.83(t,J＝7.3Hz,1H),2.29(s,3H),1.52(s,9H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝164.91,153.50,143.73,141.23,129.08,120.62,117.10,97.97,80.89,28.56,12.41ppm.
Spectroscopic data for Compound 4s ：1H NMR(600MHz,CDCl3,25℃)δ＝8.30(s,1H),7.50(d,J＝7.2Hz,2H),7.28(q,J＝7.9,6.6Hz,2H),6.92(d,J＝6.7Hz,1H),3.88(s,3H),3.55(p,J＝6.9Hz,1H),1.27(d,J＝7.1Hz,6H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.74,154.05,153.23,141.13,129.05,120.74,117.30,95.31,51.10,26.14,21.13ppm.
Spectroscopic data for Compound 4t ：1H NMR(600MHz,CDCl3,25℃)δ＝8.29(s,1H),7.48(d,J＝8.0Hz,2H),7.26(t,J＝7.6Hz,2H),6.90(t,J＝7.3Hz,1H),5.21(hept,J＝6.1Hz,1H),2.28(s,3H),1.35(d,J＝6.4Hz,6H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.20,153.72,143.98,141.16,129.12,120.73,117.11,97.01,67.49,22.22,12.16ppm.
Spectroscopic data for Compound 4u ：1H NMR(600MHz,DMSO-d6,25℃)δ＝12.38(s,1H),9.24(s,1H),8.39(s,1H),7.68–7.61(m,2H),7.43(d,J＝7.9Hz,2H),7.40–7.35(m,2H),7.27–7.17(m,2H),6.79(s,1H),2.50(s,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝164.01,152.42,142.91,140.22,138.38,129.28,128.94,127.33,122.24,119.62,116.30,101.64,11.83ppm.
Spectroscopic data for Compound 4v ：1H NMR(600MHz,CDCl3,25℃)δ＝8.11(s,1H),7.42–7.38(m,2H),7.22–7.18(m,2H),6.84(td,J＝7.4,1.2Hz,1H),4.34(t,J＝7.1Hz,2H),3.63(t,J＝7.1Hz,2H),3.36(s,3H),2.31(s,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.09,153.57,144.42,141.11,129.09,120.80,117.19,96.66,70.65,62.63,58.98,12.12ppm.
Spectroscopic data for Compound 4w ：1H NMR(600MHz,DMSO-d6,25℃)δ＝7.50(dd,J＝8.6,2.5Hz,2H),7.44–7.39(m,2H),7.25–7.20(m,2H),7.13(d,J＝8.3Hz,2H),6.80(tt,J＝7.3,1.2Hz,1H),2.53(s,3H),2.27(s,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝163.73,142.93,136.63,132.81,132.79,129.37,129.24,120.78,120.67,119.56,116.14,101.79,20.75,11.70ppm.
Spectroscopic data for Compound 4x ：1H NMR(600MHz,CDCl3,25℃)δ＝8.46(s,1H),7.55(d,J＝6.9Hz,2H),7.50(d,J＝7.4Hz,2H),7.44(dd,J＝13.4,6.7Hz,3H),7.27(d,J＝7.9Hz,2H),6.94(t,J＝7.0Hz,1H),4.22(q,J＝7.0Hz,2H),1.18(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝165.08,154.07,146.50,140.76,129.66,129.33,129.22,129.18,128.19,121.13,117.60,96.24,60.15,14.00ppm.
Spectroscopic data for Compound 4y ：1H NMR(600MHz,DMSO-d6,25℃)δ＝13.30(s,1H),8.50(d,J＝8.1Hz,1H),8.26(s,1H),7.63(d,J＝7.9Hz,2H),7.30(t,J＝7.7Hz,2H),6.90(t,J＝7.3Hz,1H),4.11(q,J＝7.1Hz,2H),1.04(t,J＝7.2Hz,3H)ppm.13C NMR(151MHz,DMSO-d6,25℃)δ＝163.95,153.52(d,J＝258.4Hz),153.37,143.62,141.59,138.00,137.37(d,J＝20.3Hz),130.97(d,J＝21.7Hz),129.93,129.39,127.42,120.60,98.20,60.32,14.13ppm.19F NMR(565MHz,DMSO-d6,25℃)δ＝122.49ppm.
Spectroscopic data for Compound 4z ：1H NMR(600MHz,CDCl3,25℃)δ＝8.24(s,1H),7.42–7.35(m,3H),7.31–7.27(m,2H),7.23–7.20(m,1H),7.19–7.14(m,2H),6.85(t,J＝7.3Hz,1H),4.03(q,J＝7.1Hz,2H),0.95(t,J＝7.1Hz,3H)ppm.13C NMR(151MHz,CDCl3,25℃)δ＝171.30,164.87,153.12,143.69,140.70,134.14,131.54,130.60,129.46,129.17,126.35,121.18,117.51,97.79,59.94,13.72ppm.
The basic synthesis method described in reference to examples 1 to 6, and the combination of structural features of the compounds with different conventional chemical raw materials, can facilitate the preparation of polysubstituted aminopyrazole compounds with diverse structures. The various reaction materials disclosed in the present invention, such as hydrazine hydrate, substituted isothiocyanate, 1, 3-dicarbonyl compound, etc., are commercially available, and the purity is preferably of analytical grade. The prepared compound can be used as a precursor molecule or a key intermediate for further preparing or constructing novel heterocyclic pyrazole drug molecule cut blocks.
Example 8
In order to further prove the functionality of the polysubstituted aminopyrazole compound prepared by the application, the in vitro MTT method is adopted to determine the in vitro growth inhibition effect of the polysubstituted aminopyrazole compound on human hepatoma cells (HepG 2) and human melanoma cells (A875).
TABLE 1 inhibition Activity of partially polysubstituted aminopyrazoles on different tumor cells
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As can be seen from Table 1, the polysubstituted aminopyrazole compounds 4a, 4b, 4e, 4ea, 4ec, 4f, 4g, 4h, 4j, 4n, 4o, 4q, 4s, 4t and 4z have different degrees of inhibition effects on cancer cells to be tested, and particularly, the inhibition activities of the compounds 4ec, 4h, 4s and 4z are obvious, the IC 50 values of the compounds are lower than 5 mu g/mL, and the application value is obvious.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (2)
1. The polysubstituted aminopyrazole compound is characterized in that the polysubstituted aminopyrazole compound is a compound with the number of 4a, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4b, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4e, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4ea, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4ec and has the structural formula:
or the polysubstituted aminopyrazole compound is a compound with the number of 4f, and the structural formula is as follows:
Or the polysubstituted aminopyrazole compound is a compound with the number of 4g, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4ga, and the structural formula is as follows:
Or the polysubstituted aminopyrazole compound is a compound with the number of 4h, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4j, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4n, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4o, and the structural formula is as follows:
Or the polysubstituted aminopyrazole compound is a compound with the number of 4q, and the structural formula is as follows:
Or the polysubstituted aminopyrazole compound is a compound with the number of 4s, and the structural formula is as follows:
or the polysubstituted aminopyrazole compound is a compound with the number of 4t, and the structural formula is as follows:
Or the polysubstituted aminopyrazole compound is a compound with the number of 4z, and the structural formula is as follows:
2. use of a polysubstituted aminopyrazole according to claim 1 for the preparation of an anticancer drug, said cancer being selected from human liver cancer or human melanoma.
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