CN108033897B - Naphthalic hydrazide compound and preparation method thereof - Google Patents
Naphthalic hydrazide compound and preparation method thereof Download PDFInfo
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- CN108033897B CN108033897B CN201711418654.6A CN201711418654A CN108033897B CN 108033897 B CN108033897 B CN 108033897B CN 201711418654 A CN201711418654 A CN 201711418654A CN 108033897 B CN108033897 B CN 108033897B
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title abstract description 9
- -1 naphthohydrazide compound Chemical class 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 239000011630 iodine Chemical group 0.000 claims description 4
- 229910052740 iodine Chemical group 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000003814 drug Substances 0.000 abstract description 10
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 6
- 230000000843 anti-fungal effect Effects 0.000 abstract description 6
- 230000000845 anti-microbial effect Effects 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 241000222122 Candida albicans Species 0.000 abstract description 5
- 241000191967 Staphylococcus aureus Species 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 229940095731 candida albicans Drugs 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 241000228197 Aspergillus flavus Species 0.000 abstract description 4
- 244000063299 Bacillus subtilis Species 0.000 abstract description 4
- 235000014469 Bacillus subtilis Nutrition 0.000 abstract description 4
- 241000235646 Cyberlindnera jadinii Species 0.000 abstract description 4
- 241000588724 Escherichia coli Species 0.000 abstract description 4
- 241000191938 Micrococcus luteus Species 0.000 abstract description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 abstract description 4
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 abstract description 4
- 241000894006 Bacteria Species 0.000 abstract description 3
- 241000233866 Fungi Species 0.000 abstract description 3
- 241000589517 Pseudomonas aeruginosa Species 0.000 abstract description 3
- 229940121375 antifungal agent Drugs 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 3
- 241000192125 Firmicutes Species 0.000 abstract description 2
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 abstract description 2
- 241000588767 Proteus vulgaris Species 0.000 abstract description 2
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 229960003085 meticillin Drugs 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 229940007042 proteus vulgaris Drugs 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- VMFUMDXVTKTZQY-UHFFFAOYSA-N naphthalene-1-carbohydrazide Chemical compound C1=CC=C2C(C(=O)NN)=CC=CC2=C1 VMFUMDXVTKTZQY-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 101100011511 Mus musculus Elovl6 gene Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- MOBRMRJUKNQBMY-UHFFFAOYSA-N 1-(chloromethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CCl MOBRMRJUKNQBMY-UHFFFAOYSA-N 0.000 description 1
- JJWDELPVPRCLQN-UHFFFAOYSA-N 1-ethyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 JJWDELPVPRCLQN-UHFFFAOYSA-N 0.000 description 1
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- LEVSFIPVEIPCIQ-UHFFFAOYSA-N 2-amino-6-bromo-4H-benzo[h]isoquinoline-1,3-dione Chemical compound C1C2=C(C3=CC=CC=C3C(=C2)Br)C(=O)N(C1=O)N LEVSFIPVEIPCIQ-UHFFFAOYSA-N 0.000 description 1
- 241000589220 Acetobacter Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- ZQWVFLUAJHYMDO-UHFFFAOYSA-N C1C2=C(C3=CC=CC=C3C(=C2)Br)C(=O)N(C1=O)NCC4=CC=CC=C4F Chemical compound C1C2=C(C3=CC=CC=C3C(=C2)Br)C(=O)N(C1=O)NCC4=CC=CC=C4F ZQWVFLUAJHYMDO-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- XJHABGPPCLHLLV-UHFFFAOYSA-N benzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(=O)NC2=O)=C3C2=CC=CC3=C1 XJHABGPPCLHLLV-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229940097572 chloromycetin Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 229960004884 fluconazole Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 229940081969 saccharomyces cerevisiae Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C241/04—Preparation of hydrazides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/38—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to a naphthahydrazide compound and a preparation method thereof, the structure of the naphthahydrazide compound is shown as formula 1, the compound has simple structure and stronger in-vitro antimicrobial activity, and particularly shows high inhibitory activity on gram-positive bacteria such as staphylococcus aureus, methicillin-resistant staphylococcus aureus, bacillus subtilis, micrococcus luteus and the like, gram-negative bacteria such as escherichia coli, proteus vulgaris, pseudomonas aeruginosa, salmonella typhi and the like, and fungi such as candida utilis, aspergillus flavus, saccharomyces cerevisiae, candida albicans and the like, and can be used for preparing antibacterial and/or antifungal medicaments. In addition, the preparation method of the naphthohydrazide compound provided by the invention has the advantages of easily available raw materials, short synthesis route, simple and convenient process, low cost and industrial production.
Description
Technical Field
The invention belongs to the field of chemical synthesis of medicines, relates to a naphthalimide compound and also relates to a preparation method of the compound.
Background
The naphthohydrazide is used as a condensed ring of a benzene ring and a benzene ring, has a large conjugated structure and strong intramolecular electron transfer capability, and can form a hydrogen bond with enzymes, receptors and the like in organisms, coordinate with metal ions, and generate hydrophobic effect, pi-pi accumulation, electrostatic effect and the like due to the special structure of the naphthohydrazide. Therefore, the naphthalimide compound can generate a plurality of non-covalent bond interactions, shows certain special performances, and shows wide application prospects and huge development values in a plurality of fields such as medicine, pesticide, chemistry, physics and the like.
In recent years, drug molecules constructed with a naphthohydrazide ring exhibit a wide range of biological activities, such as antiviral, anticancer, anti-inflammatory, analgesic, antiparasitic, and the like. Due to the wide application of the naphthalimide compound, countless researchers are attracted and encouraged to research and develop the naphthalimide compound, so that the research of the medicine containing the naphthalimide structural fragment becomes one of the active fields of the current medicine research and development. Therefore, it is still an unsolved technical problem for those skilled in the art how to optimize the structure of the naphthohydrazide compound in order to obtain a novel naphthohydrazide derivative with a mechanism of action different from that of the traditional medicine.
Disclosure of Invention
In view of the above, an object of the present invention is to provide a novel naphthohydrazide compound with high antibacterial and antifungal activities, which overcomes the disadvantages of low antibacterial and antifungal activities of naphthohydrazide compounds in the prior art; the invention also aims to provide a preparation method of the novel naphthalimide compound, which has the advantages of simple synthesis, mild conditions and convenience for large-scale synthesis.
In order to achieve the purpose, the invention provides the following technical scheme:
1. the structure of the naphthalimide compound and the pharmaceutically acceptable salt thereof is shown as the formula I:
r is fluorine, chlorine or iodine.
Preferably, R is 2-fluoro, 3-fluoro or 4-fluoro.
More preferably, R is 2-fluoro or 3-fluoro.
2. The preparation method of the naphthalimide compound and the pharmaceutically acceptable salt thereof comprises the following specific steps: adding a compound II and inorganic base into the organic solvent, and reacting under stirring at 50-70 ℃ to form a reaction solution to obtain a product I;
r is fluorine, chlorine or iodine.
Preferably, the organic solvent is one or more of N, N-dimethylformamide, methanol, ethanol or acetonitrile; the inorganic base is one or more of potassium carbonate, sodium bicarbonate or sodium hydroxide.
The invention has the beneficial effects that: the naphthohydrazide compound provided by the invention has a simple structure, has strong in-vitro antimicrobial activity, particularly shows high inhibitory activity on gram-positive bacteria such as staphylococcus aureus, methicillin-resistant staphylococcus aureus, bacillus subtilis, micrococcus luteus and the like, gram-negative bacteria such as escherichia coli, proteus bacillus, pseudomonas aeruginosa, salmonella typhi and the like, and fungi such as candida utilis, aspergillus flavus, saccharomyces cerevisiae, candida albicans and the like, can be used for preparing antibacterial and/or antifungal medicaments, provides more efficient and safe candidate medicaments for clinical antimicrobial treatment, and is beneficial to solving clinical treatment problems of increasingly severe drug resistance, stubborn pathogenic microorganisms, newly-appeared harmful microorganisms and the like.
In addition, the preparation method of the naphthohydrazide compound provided by the invention has the advantages of easily available raw materials, short synthesis route, simple and convenient process, low cost and industrial production.
Detailed Description
The technical solutions of the present invention will be described clearly and completely below, and it should be apparent that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. In addition, the technical features involved in the different embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The naphthohydrazide compound described in this example has a structure shown in formula I:
r represents fluorine.
Example 1
Preparation of naphthamide compound I-1, the reaction formula is shown below:
the method comprises the following specific steps: 1.201g of 6-bromo-2- (2-fluorobenzylamino) -1H-benzisoquine-1, 3(2H) -dione II-1, 0.144g of sodium hydroxide and 40mL of N, N-dimethylformamide are added into a 100mL round bottom flask, the temperature is controlled at 80 ℃ for reaction, thin layer chromatography is carried out until the reaction is finished, the temperature is cooled to room temperature (18-25 ℃), the N, N-dimethylformamide is removed by reduced pressure distillation, and the residue is purified by silica gel column chromatography by using a mixed solution of dichloromethane and petroleum ether with a volume ratio of 2:1 as an eluent, and is dried to obtain 0.674g of yellow solid naphthamide compound I-1.
The yield of the example is 52%; melting point 138-140 ℃;1H NMR(400MHz,CDCl3)δppm:5.27(s,2H,CH2),7.21-7.05(m,4H,2-FPh-3,4,5,6-H),
7.39-7.33(m,2H,naphthalene-7,8-H),7.59-7.50(m,2H,naphthalene-2,3-H),7.88(d,H,J＝4.0Hz,naphthalene-4-H),10.54(s,H,CHO)。
wherein the starting material 6-bromo-2- (2-fluorobenzylamino) -1H-benzisoquinoline-1, 3(2H) -dione II-1 is prepared by N-alkylation of 2-amino-6-bromo-1H-benzisoquinoline-1, 3(2H) -dione with 2-fluorobenzyl chloride by the literature method (Lv J.S.; Peng X.M.; Kishore B.; Zhou C.H.1,2, 3-Triazol-derivative compounds as a novel type of porous antimicrobial agents: Synthesis, antimicrobial activity, interaction with calcium DNA and human server emulsion, biological & Medicinal Chemistry Letters,2014,24:308 + 313).
Example 2
Naphthamide compound I-2, the reaction formula is as follows:
the method comprises the following specific steps:
1.195g of 6-bromo-2- (4-fluorobenzylamino) -1H-benzisoquine-1, 3(2H) -dione II-2, 0.154g of sodium hydroxide and 40mL of N, N-dimethylformamide are added into a 100mL round bottom flask, the temperature is controlled at 80 ℃ for reaction, thin layer chromatography is carried out until the reaction is finished, the mixture is cooled to room temperature (18-25 ℃), the N, N-dimethylformamide is removed by reduced pressure distillation, and the residue is purified by silica gel column chromatography by using a mixed solution of dichloromethane and petroleum ether with a volume ratio of 2:1 as an eluent, and is dried to obtain 0.614g of yellow solid naphthamide compound I-2.
This example yield was 52%; melting point 116-;1H NMR(400MHz,CDCl3)δppm:5.11(s,2H,CH2),7.12-7.06(m,4H,4-FPh-2,3,5,6-H),7.43-7.40(m,2H,naphthalene-7,8-H),7.61-7.57(m,2H,naphthalene-2,3-H),7.86(d,H,J＝4.0Hz,naphthalene-4-H),9.90(s,H,CHO)。
example 3
The naphthoyl hydrazide compounds prepared in examples 1-2 were tested for in vitro antimicrobial activity by a 96-well microdilution method meeting the clinical Laboratory Standards (NCCLS) established by the National Committee of america in 1993, and the Minimum Inhibitory Concentrations (MICs) of these compounds against staphylococcus aureus, MASR, micrococcus luteus, bacillus subtilis, escherichia coli, pseudomonas aeruginosa, proteus vulgaris, candida utilis, aspergillus flavus, saccharomyces cerevisiae, candida albicans, and candida albicans were examined.
The specific test method comprises the following steps: dissolving the compound to be tested with a small amount of dimethyl sulfoxide, adding water to dilute the solution to obtain a solution with the concentration of 1.28mg/mL, diluting the solution to 1024 mu g/mL with a culture solution, culturing the solution at 35 ℃ for 24-72 hours, placing a culture plate on an oscillator, fully and uniformly stirring the culture plate, and measuring the MIC value at the 490nm wavelength, wherein the results are shown in tables 1 and 2.
TABLE 1 antibacterial Activity (MIC, μ g/mL) of naphthohydrazide Compounds I-1, I-2
| Compound (I) | Golden yellow grapeStaphylococcus aureus | MASR | Micrococcus luteus | Bacillus subtilis | Escherichia coli | Pseudomonas aeruginosa | Proteobacteria |
| I-1 | 8 | 16 | 4 | 16 | 16 | 16 | 8 |
| I-2 | 16 | 32 | 8 | 16 | 32 | 32 | 16 |
| Chloromycetin | 16 | 32 | 8 | 32 | 32 | 32 | 32 |
| Norfloxacin hydrochloride | 1 | 8 | 2 | 4 | 2 | 2 | 4 |
TABLE 2 antifungal Activity (MIC, μ g/mL) of naphthohydrazide Compounds I-1, I-2
| Compound (I) | Candida utilis | Aspergillus flavus | Beer yeast | Candida albicans | Candida mycoderma |
| I-1 | 4 | 16 | 8 | 4 | 4 |
| I-2 | 8 | 64 | 8 | 8 | 8 |
| Fluconazole | 8 | 256 | 16 | 4 | 8 |
As can be seen from Table 1, the naphthoyl hydrazide compounds all show moderate inhibitory action on tested bacteria, and Table 2 shows that the naphthoyl hydrazide compounds all show certain inhibitory action on tested fungi, so that the naphthoyl hydrazide compounds provided by the invention have strong antimicrobial activity and can be used for preparing antibacterial and/or antifungal medicaments.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (5)
1. The naphthalimide compound and the medicinal salt thereof are characterized in that: the structure is shown as formula I:
r is fluorine, chlorine or iodine.
2. The naphthohydrazide-type compound and the pharmaceutically acceptable salt thereof as claimed in claim 1, wherein: r is 2-fluoro, 3-fluoro or 4-fluoro.
3. The naphthohydrazide-type compound and the pharmaceutically acceptable salt thereof as claimed in claim 1, wherein: r is 2-fluoro or 3-fluoro.
4. A process for preparing a naphthohydrazide compound as claimed in any one of claims 1 to 3, wherein: the method comprises the following specific steps: adding a compound II and inorganic base into an organic solvent, and reacting at 50-70 ℃ under stirring to form a reaction solution to obtain a product I;
r is fluorine, chlorine or iodine.
5. The process for preparing naphthohydrazide compound and pharmaceutically acceptable salts thereof as claimed in claim 4, wherein: the organic solvent is one or more of N, N-dimethylformamide, methanol, ethanol or acetonitrile; the inorganic base is one or more of potassium carbonate, sodium bicarbonate or sodium hydroxide.
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| CA2703018A1 (en) * | 2007-05-03 | 2008-11-13 | Northeastern University | Methods of treating fungal infections |
| AU2008264580A1 (en) * | 2007-06-18 | 2008-12-24 | Kaken Pharmaceutical Co., Ltd. | Azolylmethylenehydrazine derivative and use thereof |
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