CN105541808A - Metronidazole-isatin type compound as well as preparation method and application thereof - Google Patents

Metronidazole-isatin type compound as well as preparation method and application thereof Download PDF

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CN105541808A
CN105541808A CN201610080048.7A CN201610080048A CN105541808A CN 105541808 A CN105541808 A CN 105541808A CN 201610080048 A CN201610080048 A CN 201610080048A CN 105541808 A CN105541808 A CN 105541808A
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methyl
isatin
preparation
nitro
imidazoles
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王广成
彭知云
李欣
李涓
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Jishou University
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Jishou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The invention discloses a metronidazole-isatin type compound as well as a preparation method and an application thereof. The compound has a structure represented by a formula (I) (shown in the specification). The preparation method comprises the following steps: preparing 2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyl-4-methyl benzenesulfonate from metronidazole and paratoluensulfonyl chloride serving as raw materials, and reacting by virtue of cesium carbonate serving as alkali, N,N-dimethyl formamide serving as a solvent and p-hydroxy benzaldehyde, so as to obtain 4-(2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyoxyl)benzaldehyde; carrying out dehydration condensation on isatin, a derivative of isatin and hydrazine hydrate so as to obtain an intermediate, and carrying out dehydration condensation on the intermediate and 4-(2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethyoxyl)benzaldehyde in the presence of glacial acetic acid serving as a catalyst, so as to obtain the target product. The compound can be used as a raw material of antibacterial drugs; and in the preparation method, the raw materials are simple and easily available, and the operation is convenient.

Description

A kind of metronidazole-isatin type compound and method for making thereof and purposes
Technical field
The present invention relates to a kind of metronidazole-isatin type compound and preparation method thereof and the application in preparation antibacterials.
Background technology
Along with the widespread use of antibacterials, especially antibiotic abuse, the drug resistance problems of worldwide bacterium is day by day serious in recent years, and presents the trend risen year by year, brings great difficulty to the treatment of infectious diseases.The particularly appearance of the Multidrug resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), penicillin resistance pneumococcus (PRSP), multiple-drug resistance tuberculosis bacillus, the life and health of the serious threat mankind.
Isatin has another name called isatin or 2,3-indolinedione, is present in various natural products, is a kind of common Structures of Natural Products.According to the literature, isatin and derivative thereof have multiple biological activity, as spasmolytic, tuberculosis, antibacterium, antimycotic, antiviral, antitumor etc.
Metronidazole is also known as making Metronidazole plain BP.98 99, it is nitro imidazole derivatives, it has the effect of wide spectrum anaerobe resistant, such as: gram positive organism (as perfringens bacillus and destroy chain coccus etc.) and Grain-negative anerobe (as Prey irrigates Pseudomonas and Fusobacterium etc.), the infection etc. of the infection of anerobe and the microbial septicemia of anaerobism after being mainly used to prevention and therapy surgery, gynaecology and obstetrics operation in clinical, joint and bone.Metronidazole derivative has good anti-microbial activity, take metronidazole as lead compound, research obtains a large amount of nitro glyoxaline antibacterials, as tinidazole (tinidazole), ornidazole (ornidazole), secnidazole (secnidazole) go on the market abroad, be used for the treatment of parasitic infection and protozoan infection.Based on above analysis, we, according to twin medicine principle, design and are connected with isatin structure by metronidazole, design and synthesis a kind of metronidazole of novel structure-isatin type compound.
Summary of the invention
Technical scheme of the present invention is as follows:
A kind of metronidazole-isatin type compound, is characterized in that they have general structure as shown in the formula (I):
（I）
Wherein: R 1for hydrogen, alkyl, benzyl or substituted benzyl, R 2, R 3, R 4or R 5for hydrogen, fluorine, chlorine, bromine, alkyl, alkoxyl group or nitro.
Prepare a method for above-mentioned metronidazole-isatin type compound, it comprises the following steps:
Step 1: metronidazole, pyridine, Tosyl chloride are placed in round-bottomed flask, stirred at ambient temperature reaction 8-20h, reaction solution is poured in suitable quantity of water, crystallize out, suction filtration, uses suitable quantity of water washing leaching cake, dries, obtain pressed powder 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester, described metronidazole, the mol ratio of Tosyl chloride are 1:(1 ~ 10);
Step 2: p-Hydroxybenzaldehyde, cesium carbonate, 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester are placed in round-bottomed flask, add N, dinethylformamide, be warming up to 50-100 DEG C of reaction 5-24h, add water, extraction into ethyl acetate, merge organic phase, cross silica gel chromatography, obtain solid 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde; The mol ratio of described p-Hydroxybenzaldehyde, 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester, cesium carbonate is 1:(1 ~ 4): (1 ~ 5);
Step 3: replacement isatin, hydrazine hydrate are placed in round-bottomed flask, add methyl alcohol, back flow reaction 3-8h, stopped reaction, cool to room temperature, by reaction solution suction filtration, uses proper amount of methanol washing leaching cake, dries, and obtains pressed powder and replaces 3-hydrazono-indole-2-ketone; Described replacement isatin, the mol ratio of hydrazine hydrate are 1:(1 ~ 4);
Step 4: 3-hydrazono-indole-2-ketone will be replaced, 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde, glacial acetic acid be placed in round-bottomed flask, add ethanol, temperature rising reflux, reaction 2-10h, stopped reaction, after cool to room temperature, suction filtration, use ethanol in proper amount washing leaching cake, obtain thick product, obtain pressed powder metronidazole-isatin type compound (I) through purification by silica gel column chromatography; The mol ratio of described replacement 3-hydrazono-indole-2-ketone, 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde is 1:(1 ~ 5).
Metronidazole of the present invention-isatin type compound all has various bacteria and suppresses preferably and kill activity, and the development and application for antibacterials provides new selection.
Accompanying drawing explanation
Fig. 1 is the syntheti c route figure of metronidazole-isatin type compound.
Embodiment
Following embodiment is to describe the present invention in detail, and unrestricted the present invention.
The preparation of embodiment one: 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester
Metronidazole (10.00mmol), pyridine (35.0mL), Tosyl chloride (20.00mmol) are placed in round-bottomed flask, stirred at ambient temperature reaction 12h, TLC display reaction is complete, and stopped reaction, pours into reaction solution in suitable quantity of water, separate out rice white crystal, suction filtration, uses suitable quantity of water washing leaching cake, dries, obtain white solid powder 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester, productive rate 69.5%. 1HNMR(d 6-DMSO，400MHz)：δ:2.40(s,3H),2.41(s,3H),4.39(t,2H),4.55(t,2H),7.39(d,2H),7.59(d,2H),7.92(s,1H);EIMSm/z=326[M +]。
The preparation of embodiment two: 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde
By p-Hydroxybenzaldehyde (2mmol), cesium carbonate (4mmol), 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester (2mmol) is placed in round-bottomed flask, add N, dinethylformamide (5mL), be warming up to 90 DEG C of reaction 12h, TLC display reaction is complete, stopped reaction, add water, be extracted with ethyl acetate 3 times, combining extraction liquid, with anhydrous sodium sulfate drying, filter, be spin-dried for, resistates is crossed chromatography column and is separated to obtain yellow solid powder 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde, productive rate 73%. 1HNMR(d 6-DMSO,400MHz)δ:2.51(s,3H),4.48(t,2H),4.76(t,2H),7.01(d,2H),7.84(d,2H),8.04(s,1H),9.87(s,1H);EIMSm/z=276[M +]。
Embodiment three: the preparation of (E)-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (1)
Isatin (10.00mmol), hydrazine hydrate (11.00mmol) are placed in round-bottomed flask, add methyl alcohol (15.0mL), back flow reaction 3-8h, stopped reaction, cool to room temperature, by reaction solution suction filtration, uses proper amount of methanol washing leaching cake, dry, obtain yellow solid powder 3-hydrazono-indole-2-ketone; Productive rate 72%.By 3-hydrazono-indole-2-ketone (1.00mmol), 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde (1.00mmol) is placed in round-bottomed flask, add ethanol (6.0mL), glacial acetic acid (1), temperature rising reflux, reaction 4-8h, TLC display reaction is complete, stopped reaction, after cool to room temperature, suction filtration, use ethanol in proper amount washing leaching cake, obtain thick product, safran pressed powder (E)-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone must be obtained through purification by silica gel column chromatography, productive rate 62%. 1HNMR(d 6-DMSO,400MHz)δ:2.55(s,3H),4.46(t,2H),4.76(t,2H),6.91(d,1H),7.03(t,1H),7.10(d,2H),7.39(t,1H),7.94(d,2H),8.01(d,1H),8.05(s,1H),8.61(s,1H),10.86(s,1H);EIMSm/z=419[M +]。
Embodiment four: the preparation of (E)-7-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (2)
Preparation method is with embodiment three, and just isatin replaces with 7-methylisatin, yield 66%. 1HNMR(d 6-DMSO,400MHz)δ:2.20(s,3H),2.55(s,3H),4.45(t,2H),4.75(t,2H),6.94(t,1H),7.10(d,2H),7.23(d,1H),7.85(d,1H),7.93(d,2H),8.05(s,1H),8.58(s,1H),10.88(s,1H);EIMSm/z=433[M +]。
Embodiment five: the preparation of (E)-1-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (3)
Preparation method is with embodiment three, and just isatin replaces with 1-methylisatin, yield 80%. 1HNMR(d 6-DMSO,400MHz)δ:2.55(s,3H),3.65(s,3H),4.46(t,2H),4.76(t,2H),6.93(d,1H),7.13(t,1H),7.10(d,2H),7.49(t,1H),7.94(d,2H),8.03(d,1H),8.05(s,1H),8.61(s,1H);EIMSm/z=433[M +]。
Embodiment six: the preparation of (E)-7-ethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (4)
Preparation method is with embodiment three, and just isatin replaces with 7-ethyl isatin, yield 75%. 1HNMR(d 6-DMSO,400MHz)δ:1.75(t,3H),2.54(s,3H),3.14(q,2H),4.47(t,2H),4.78(t,2H),6.93(d,1H),7.02(t,1H),7.11(d,2H),7.36(d,1H),7.92(d,2H),8.04(s,1H),8.62(s,1H),10.85(s,1H);EIMSm/z=447[M +]。
Embodiment seven: the preparation of (E)-1-ethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (5)
Preparation method is with embodiment three, and just isatin replaces with 1-ethyl isatin, yield 65%. 1HNMR(d 6-DMSO,400MHz)δ:1.71(t,3H),2.53(s,3H),4.44(t,2H),4.78(q,2H),4.82(t,2H),4.79(t,2H),6.90(d,1H),7.02(t,1H),7.13(d,2H),7.42(t,1H),7.96(d,2H),8.03(d,1H,14),8.05(s,1H),8.61(s,1H);EIMSm/z=447[M +]。
Embodiment eight: the preparation of (E)-7-propyl group-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (6)
Preparation method is with embodiment three, and just isatin replaces with 7-propyl group isatin, yield 78%. 1HNMR(d 6-DMSO,400MHz)δ:1.65(t,3H),2.25(m,2H),2.57(s,3H),3.12(t,2H),4.47(t,2H),4.78(t,2H),6.92(d,1H),7.03(t,1H),7.15(d,2H),7.36(d,1H),7.98(d,2H),8.05(s,1H),8.64(s,1H),10.84(s,1H);EIMSm/z=461[M +]。
Embodiment nine: the preparation of (E)-1-propyl group-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (7)
Preparation method is with embodiment three, and just isatin replaces with 1-propyl group isatin, yield 82%. 1HNMR(d 6-DMSO,400MHz)δ: 1HNMR(CDCl 3,400MHz)δ:1.70(t,3H),2.23(m,2H),2.58(s,3H),4.49(t,2H),4.72(t,2H),4.78(t,2H),6.96(d,1H),7.04(t,1H),7.11(d,2H),7.43(t,1H,),7.98(d,2H),8.06(d,1H),8.09(s,1H),8.66(s,1H);EIMSm/z=461[M +]。
Embodiment ten: the preparation of (E)-5-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (8)
Preparation method is with embodiment three, and just isatin replaces with 5-methylisatin, yield 84%. 1HNMR(d 6-DMSO,400MHz)δ:2.25(s,3H),2.55(s,3H),4.46(t,2H),4.76(t,2H),6.80(d,1H),7.12(d,2H),7.22(d,1H),7.82(d,1H),7.94(d,2H),8.05(s,1H),8.60(s,1H),10.73(s,1H);EIMSm/z=433[M +]。
Embodiment 11: (E)-5,7-preparation of dimethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (9)
Preparation method is with embodiment three, and just isatin replaces with 5,7-dimethylisatin, yield 68%. 1HNMR(d 6-DMSO,400MHz)δ:2.17(s,6H),2.22(s,3H),4.75(t,4H),7.06-7.14(m,4H),7.79(d,2H),7.93(d,2H),10.79(s,1H);EIMSm/z=447[M +]。
Embodiment 12: (E)-1, the preparation of 5,7-trimethylammonium-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (10)
Preparation method is with embodiment three, and just isatin replaces with 1,5,7-trimethylammonium isatin, yield 73%. 1HNMR(d 6-DMSO,400MHz)δ:2.52(s,3H),2.84(s,3H),2.94(s,3H),3.72(s,3H),4.96(t,2H),5.06(t,2H),7.10(d,2H),7.69(d,1H),7.90(d,2H),7.95(d,1H),8.12(s,1H),8.61(s,1H);EIMSm/z=461[M +]。
Embodiment 13: the preparation of (E)-5-ethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (11)
Preparation method is with embodiment three, and just isatin replaces with 5-ethyl isatin, yield 76%. 1HNMR(d 6-DMSO,400MHz)δ:1.75(t,3H),2.51(s,3H),3.11(q,2H),4.49(t,2H),4.66(t,2H),7.13(d,2H),7.98(d,2H),7.82(d,1H),7.86(d,1H),7.92(d,1H),8.15(s,1H),8.91(s,1H),10.89(s,1H);EIMSm/z=447[M +]。
Embodiment 14: the preparation of (E)-5-ethyl-7-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (12)
Preparation method is with embodiment three, and just isatin replaces 5-ethyl-7-methylisatin, yield 78%. 1HNMR(d 6-DMSO,400MHz)δ:1.78(t,3H),2.51(s,3H),2.63(s,3H),3.12(q,2H),4.48(t,2H),4.88(t,2H),7.15(d,2H),7.83(d,1H),7.91(d,1H),7.99(d,2H),8.07(s,1H),8.67(s,1H),10.36(s,1H);EIMSm/z=461[M +]。
Embodiment 15: the preparation of (E)-1-methyl-5-ethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (13)
Preparation method is with embodiment three, and just isatin replaces 1-methyl-5-ethyl isatin, yield 80%. 1HNMR(d 6-DMSO,400MHz)δ:1.75(t,3H),2.53(s,3H),3.93(s,3H),3.13(q,2H),4.49(t,2H),4.88(t,2H),7.17(d,2H),7.83(d,1H),7.98(d,2H),8.21(d,1H),8.26(d,1H),8.45(s,1H),8.71(s,1H);EIMSm/z=461[M +]。
Embodiment 16: (E)-1,7-preparation of dimethyl-5-ethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (14)
Preparation method is with embodiment three, and just isatin replaces 1,7-dimethyl-5-ethyl isatin, yield 88%. 1HNMR(d 6-DMSO,400MHz)δ:1.77(t,3H),2.52(s,3H),2.62(s,3H),3.94(s,3H),3.12(q,2H),4.49(t,2H),4.79(t,2H),7.17(d,2H),7.72(d,1H),7.98(d,2H),8.01(d,1H),8.07(s,1H),8.69(s,1H);EIMSm/z=475[M +]。
Embodiment 17: the preparation of the fluoro-3-of (E)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (15)
Preparation method is with embodiment three, and just isatin replaces 5-fluoro indigo red, yield 57%. 1HNMR(d 6-DMSO,400MHz)δ:2.55(s,3H),4.47(t,2H),4.76(t,2H),6.92(q,1H),7.10-7.15(m,2H),7.31(q,1H),7.78(dd,1H),7.95(d,2H),8.05(d,1H),9.86(s,1H),10.89(s,1H);EIMSm/z=437[M +]。
Embodiment 18: the preparation of the fluoro-3-of the chloro-5-of (E)-7-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (16)
Preparation method is with embodiment three, and just isatin replaces the chloro-5-fluoro indigo red of 7-, yield 76%. 1HNMR(d 6-DMSO,400MHz)δ:2.57(s,3H),4.40(t,2H),4.72(t,2H),6.99(d,1H),7.14(d,2H),7.69(d,1H),7.90(d,2H),8.07(s,1H),8.68(s,1H),10.80(s,1H);EIMSm/z=471[M +]。
Embodiment 19: the preparation of the fluoro-1-methyl of (E)-5--3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (17)
Preparation method is with embodiment three, and just isatin replaces the fluoro-1-methylisatin of 5-, yield 79%. 1HNMR(d 6-DMSO,400MHz)δ:2.51(s,3H),3.49(s,3H),4.43(t,2H),4.86(t,2H),7.17(d,2H),7.34(d,1H),7.71(d,1H),7.89(d,1H),7.99(d,2H),8.09(s,1H),8.67(s,1H);EIMSm/z=451[M +]。
Embodiment 20: the preparation of the fluoro-1-methyl of the chloro-5-of (E)-7--3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (18)
Preparation method is with embodiment three, and just isatin replaces the fluoro-1-methylisatin of the chloro-5-of 7-, yield 70%. 1HNMR(d 6-DMSO,400MHz)δ:2.45(s,3H),3.41(s,3H),4.56(t,2H),4.86(t,2H),7.16(d,2H),7.29(d,1H),7.67(d,1H),7.84(d,2H),8.01(s,1H),8.71(s,1H);EIMSm/z=485[M +]。
Embodiment 21: the preparation of the chloro-3-of (E)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (19)
Preparation method is with embodiment three, and just isatin replaces 5-chlorisatide, yield 72%. 1HNMR(d 6-DMSO,400MHz)δ:2.56(s,3H),4.48(t,2H),4.77(t,2H),6.94(d,1H),7.16(d,2H),7.48(dd,1H),7.94(d,2H),7.98(d,1H),8.06(s,1H),8.68(s,1H),11.01(s,1H);EIMSm/z=453[M +]。
Embodiment 22: (E)-5,7-bis-preparation of chloro-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (20)
Preparation method is with embodiment three, and just isatin replaces 5,7-bis-chlorisatide, yield 85%. 1HNMR(d 6-DMSO,400MHz)δ:2.75(s,3H),4.48(t,2H),4.79(t,2H),6.99(d,1H),7.12(d,2H),7.29(d,1H),7.98(d,2H),8.07(s,1H),8.66(s,1H),10.96(s,1H);EIMSm/z=488[M +]。
Embodiment 23: (E)-5,7-bis-preparation of chloro-1-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (21)
Preparation method is with embodiment three, and just isatin replaces the chloro-1-methylisatin of 5,7-bis-, yield 68%. 1HNMR(d 6-DMSO,400MHz)δ:2.46(s,3H),3.47(s,3H),4.49(t,2H),4.77(t,2H),6.98(d,1H),7.11(d,2H),7.33(d,1H),7.88(d,2H),8.08(s,1H),8.76(s,1H);EIMSm/z=502[M +]。
Embodiment 24: the preparation of the bromo-3-of (E)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (22)
Preparation method is with embodiment three, and just isatin replaces 5-bromoisatin, yield 72%. 1HNMR(d 6-DMSO,400MHz)δ:2.58(s,3H),4.42(t,2H),4.70(t,2H),6.90(d,1H),7.19(d,2H),7.49(dd,1H),7.96(d,2H),7.99(d,1H),8.09(s,1H),8.78(s,1H),11.00(s,1H);EIMSm/z=498[M +]。
Embodiment 25: (E)-5,7-bis-preparation of bromo-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (23)
Preparation method is with embodiment three, and just isatin replaces 5,7-bis-bromo-isatin, yield 85%. 1HNMR(d 6-DMSO,400MHz)δ:2.35(s,3H),4.38(t,2H),4.69(t,2H),6.79(d,1H),7.22(d,2H),7.28(d,1H),7.88(d,2H),8.03(s,1H),8.76(s,1H),10.99(s,1H);EIMSm/z=577[M +]。
Embodiment 26: (E)-5,7-bis-preparation of bromo-1-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (24)
Preparation method is with embodiment three, and just isatin replaces the bromo-1-methylisatin of 5,7-bis-, yield 68%. 1HNMR(d 6-DMSO,400MHz)δ:2.86(s,3H),3.56(s,3H),4.69(t,2H),4.97(t,2H),6.78(d,1H),7.19(d,2H),7.43(d,1H),7.98(d,2H),8.05(s,1H),8.77(s,1H);EIMSm/z=591[M +]。
Embodiment 27: the preparation of the chloro-3-of the bromo-7-of (E)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (25)
Preparation method is with embodiment three, and just isatin replaces the bromo-7-chlorisatide of 5-, yield 61%. 1HNMR(d 6-DMSO,400MHz)δ:2.67(s,3H),4.48(t,2H),4.82(t,2H),6.89(d,1H),7.16(d,2H),7.79(d,1H),7.96(d,2H),8.08(s,1H),8.78(s,1H),10.82(s,1H);EIMSm/z=532[M +]。
Embodiment 28: the preparation of the bromo-1-methyl of (E)-5--3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (26)
Preparation method is with embodiment three, and just isatin replaces the bromo-1-methylisatin of 5-, yield 73%. 1HNMR(d 6-DMSO,400MHz)δ:2.58(s,3H),3.58(s,3H),4.69(t,2H),4.96(t,2H),7.27(d,2H),7.39(d,1H),7.72(d,1H),7.82(d,1H),7.90(d,2H),8.03(s,1H),8.69(s,1H);EIMSm/z=512[M +]。
Embodiment 29: the preparation of the chloro-1-methyl of the bromo-7-of (E)-5--3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (27)
Preparation method is with embodiment three, and just isatin replaces the chloro-1-methylisatin of the bromo-7-of 5-, yield 73%. 1HNMR(d 6-DMSO,400MHz)δ:2.85(s,3H),3.35(s,3H),4.76(t,2H),4.96(t,2H),7.26(d,2H),7.39(d,1H),7.77(d,1H),7.94(d,2H),8.08(s,1H),8.79(s,1H);EIMSm/z=546[M +]。
Embodiment 30: (E)-5,7-bis-preparation of fluoro-1-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (28)
Preparation method is with embodiment three, and just isatin replaces the fluoro-1-methylisatin of 5,7-bis-, yield 65%. 1HNMR(d 6-DMSO,400MHz)δ:2.45(s,3H),3.39(s,3H),4.46(t,2H),4.76(t,2H),7.46(d,2H),7.59(d,1H),7.87(d,1H),7.99(d,2H),8.01(s,1H),8.89(s,1H);EIMSm/z=469[M +]。
Embodiment 31: the preparation of the fluoro-1-methyl of the bromo-5-of (E)-7--3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (29)
Preparation method is with embodiment three, and just isatin replaces the fluoro-1-methylisatin of the bromo-5-of 7-, yield 65%. 1HNMR(d 6-DMSO,400MHz)δ:2.40(s,3H),3.40(s,3H),4.41(t,2H),4.72(t,2H),7.43(d,2H),7.56(d,1H),7.89(d,1H),7.98(d,2H),8.02(s,1H),8.93(s,1H);EIMSm/z=530[M +]。
Embodiment 32: the preparation of (E)-1-benzyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (30)
Preparation method is with embodiment three, and just isatin replaces 1-benzyl isatin, yield 82%. 1HNMR(d 6-DMSO,400MHz)δ:2.56(s,3H),4.47(t,2H),4.77(t,2H),4.98(s,2H),7.03(d,1H),7.12(d,3H),7.28-7.42(m,8H),7.98(d,2H),8.68(s,1H);EIMSm/z=509[M +]。
Embodiment 33: the preparation of (E)-1-(2-luorobenzyl)-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (31)
Preparation method is with embodiment three, and just isatin replaces 1-(2-luorobenzyl) isatin, yield 89%. 1HNMR(d 6-DMSO,400MHz)δ:2.57(s,3H),4.48(t,2H),4.77(t,2H),5.04(s,2H),7.01(d,1H),7.12(d,3H),7.18(t,1H),7.28(d,1H),7.33-7.40(m,2H),7.44(t,1H),7.98(d,2H),8.07(s,1H),8.12(d,1H);EIMSm/z=527[M +]。
Embodiment 34: the preparation of (E)-1-(4-bromobenzyl)-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (32)
Preparation method is with embodiment three, and just isatin replaces 1-(4-bromobenzyl) isatin, yield 80%. 1HNMR(d 6-DMSO,400MHz)δ:2.59(s,3H),4.49(t,2H),4.78(t,2H),4.95(s,2H),6.92(d,1H),7.15(d,3H),7.25(s,1H),7.34(d,2H),7.56(d,2H),7.91(s,1H),7.98(d,2H),8.07(s,1H),8.68(s,1H);EIMSm/z=588[M +]。
Embodiment 35: the preparation of (E)-1-(2-chlorobenzyl)-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (33)
Preparation method is with embodiment three, and just isatin replaces 1-(2-chlorobenzyl) isatin, yield 79%. 1HNMR(d 6-DMSO,400MHz)δ:2.50(s,3H),4.47(t,2H),4.87(t,2H),5.09(s,2H),7.08(d,1H),7.19(d,3H),7.22(t,1H),7.29(d,1H),7.32-7.44(m,2H),7.49(t,1H),7.90(d,2H),8.05(s,1H),8.16(d,1H);EIMSm/z=543[M +]。
Embodiment 36: the preparation of (E)-1-(4-chlorobenzyl)-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (34)
Preparation method is with embodiment three, and just isatin replaces 1-(4-chlorobenzyl) isatin, yield 73%. 1HNMR(d 6-DMSO,400MHz)δ:2.63(s,3H),4.55(t,2H),4.88(t,2H),4.99(s,2H),6.98(d,1H),7.17(d,3H),7.26(s,1H),7.37(d,2H),7.59(d,2H),7.90(s,1H),7.98(d,2H),8.08(s,1H),8.69(s,1H);EIMSm/z=543[M +]。
Embodiment 37: the preparation of (E)-1-(2-chlorobenzyl)-5-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (35)
Preparation method is with embodiment three, and just isatin replaces 1-(2-chlorobenzyl)-5-methylisatin, yield 83%. 1HNMR(d 6-DMSO,400MHz)δ:2.28(s,3H),2.58(s,3H),4.48(t,2H),4.77(t,2H),5.02(s,2H),6.81(d,1H),7.15(d,2H),7.20(d,1H),7.24(d,1H),7.27-7.36(m,2H),7.54(d,1H),7.98(d,3H),8.07(s,1H),8.69(s,1H);EIMSm/z=558[M +]。
Embodiment 38: the preparation of (E)-1-(2-bromobenzyl)-5-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (36)
Preparation method is with embodiment three, and just isatin replaces 1-(2-bromobenzyl)-5-methylisatin, yield 77%. 1HNMR(d 6-DMSO,400MHz)δ:2.38(s,3H),2.68(s,3H),4.45(t,2H),4.87(t,2H),5.09(s,2H),6.88(d,1H),7.12(d,2H),7.25(d,1H),7.29(d,1H),7.23-7.34(m,2H),7.59(d,1H),7.90(d,3H),8.03(s,1H),8.71(s,1H);EIMSm/z=602[M +]。
Embodiment 39: the preparation of (E)-1-(4-bromobenzyl)-5-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (37)
Preparation method is with embodiment three, and just isatin replaces 1-(4-bromobenzyl)-5-methylisatin, yield 85%. 1HNMR(d 6-DMSO,400MHz)δ:2.28(s,3H),2.57(s,3H),4.48(t,2H),4.77(t,2H),4.95(s,2H),6.92(d,1H),7.03(d,2H),7.15(d,2H),7.25(d,1H),7.80(d,2H),7.98(d,2H),8.62(s,1H),8.68(s,1H);EIMSm/z=602[M +]。
Embodiment 40: the preparation of (E)-1-(4-chlorobenzyl)-5-methyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (38)
Preparation method is with embodiment three, and just isatin replaces 1-(4-chlorobenzyl)-5-methylisatin, yield 80%. 1HNMR(d 6-DMSO,400MHz)δ:2.29(s,3H),2.59(s,3H),4.48(t,2H),4.79(t,2H),4.94(s,2H),6.96(d,1H),7.04(d,2H),7.16(d,2H),7.28(d,1H),7.81(d,2H),7.98(d,2H),8.60(s,1H),8.69(s,1H);EIMSm/z=558[M +]。
Embodiment 41: the preparation of (E)-1-(2-chlorobenzyl)-5,7-dimethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (39)
Preparation method is with embodiment three, and just isatin replaces 1-(2-chlorobenzyl)-5,7-dimethylisatin, yield 83%. 1HNMR(d 6-DMSO,400MHz)δ:2.09(s,3H),2.23(s,3H),2.57(s,3H),4.49(t,2H),4.78(t,2H),5.18(s,2H),7.08(d,2H),7.16(d,2H),7.29-7.36(m,2H),7.58(d,1H),7.98(d,3H),8.07(s,1H),8.67(s,1H);EIMSm/z=572[M +]。
Embodiment 42: the preparation of (E)-1-(2-bromobenzyl)-5,7-dimethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (40)
Preparation method is with embodiment three, and just isatin replaces 1-(2-bromobenzyl)-5,7-dimethylisatin, yield 73%. 1HNMR(d 6-DMSO,400MHz)δ:2.11(s,3H),2.33(s,3H),2.67(s,3H),4.51(t,2H),4.73(t,2H),5.20(s,2H),7.11(d,2H),7.19(d,2H),7.25-7.30(m,2H),7.54(d,1H),7.88(d,3H),8.05(s,1H),8.69(s,1H);EIMSm/z=616[M +]。
Embodiment 43: the preparation of (E)-1-(4-bromobenzyl)-5,7-dimethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (41)
Preparation method is with embodiment three, and just isatin replaces 1-(4-bromobenzyl)-5,7-dimethylisatin, yield 69%. 1HNMR(d 6-DMSO,400MHz)δ:2.18(s,3H),2.24(s,3H),2.58(s,3H),4.49(t,2H),4.78(t,2H),5.17(s,2H),7.03(s,1H),7.16(d,2H),7.20(d,2H),7.57(d,2H),7.89(s,1H),7.98(d,2H),8.08(s,1H),8.66(s,1H);EIMSm/z=616[M +]。
Embodiment 44: the preparation of (E)-1-(4-chlorobenzyl)-5,7-dimethyl-3-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (42)
Preparation method is with embodiment three, and just isatin replaces 1-(4-chlorobenzyl)-5,7-dimethylisatin, yield 65%. 1HNMR(d 6-DMSO,400MHz)δ:2.12(s,3H),2.29(s,3H),2.60(s,3H),4.51(t,2H),4.82(t,2H),5.27(s,2H),7.09(s,1H),7.18(d,2H),7.28(d,2H),7.59(d,2H),7.85(s,1H),7.90(d,2H),8.03(s,1H),8.69(s,1H);EIMSm/z=572[M +]。
Embodiment 45: the preparation of the fluoro-3-of (E)-1-(2-chlorobenzyl)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (43)
Preparation method is with embodiment three, and just isatin replaces 1-(2-chlorobenzyl)-5-fluoro indigo red, yield 73%. 1HNMR(d 6-DMSO,400MHz)δ:2.55(s,3H),4.47(t,2H),4.76(t,2H),5.03(s,2H),6.94(q,1H),7.15(d,2H),7.23(d,1H),7.26-7.36(m,3H),7.54(dd,1H),7.90(dd,1H),7.99(d,2H),8.05(s,1H),8.75(s,1H);EIMSm/z=561[M +]。
Embodiment 46: the preparation of the fluoro-3-of (E)-1-(4-bromobenzyl)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (44)
Preparation method is with embodiment three, and just isatin replaces 1-(4-bromobenzyl)-5-fluoro indigo red, yield 66%. 1HNMR(d 6-DMSO,400MHz)δ:2.56(s,3H),4.48(t,2H),4.77(t,2H),4.97(s,2H),7.00-7.04(m,1H),7.15(d,2H),7.35(q,3H),7.56(d,2H),7.87(dd,1H),7.98(d,2H),8.06(s,1H),8.74(s,1H);EIMSm/z=606[M +]。
Embodiment 47: the preparation of the chloro-3-of (E)-1-(2-luorobenzyl)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (45)
Preparation method is with embodiment three, and just isatin replaces 1-(2-luorobenzyl)-5-chlorisatide, yield 68%. 1HNMR(d 6-DMSO,400MHz)δ:2.55(s,3H),4.47(t,2H),4.76(t,2H),5.03(s,2H),7.04(d,1H),7.16(d,3H),7.26(d,1H),7.32-7.36(m,2H),7.53(dd,1H),7.95(d,2H),8.06(d,2H),8.72(s,1H);EIMSm/z=561[M +]。
Embodiment 48: the preparation of the chloro-3-of (E)-1-(3-luorobenzyl)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (46)
Preparation method is with embodiment three, and just isatin replaces 1-(3-luorobenzyl)-5-chlorisatide, yield 78%. 1HNMR(d 6-DMSO,400MHz)δ:2.54(s,3H),4.41(t,2H),4.48(t,2H),5.00(s,2H),6.99-7.05(m,5H),7.16(d,2H),7.25(q,1H),7.42(q,1H),7.52(dd,1H),7.95(d,2H),8.73(s,1H);EIMSm/z=561[M +]。
Embodiment 49: the preparation of the chloro-3-of (E)-1-(4-bromobenzyl)-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (47)
Preparation method is with embodiment three, and just isatin replaces 1-(4-bromobenzyl)-5-chlorisatide, yield 62%. 1HNMR(d 6-DMSO,400MHz)δ:2.55(s,3H),4.41(t,2H),4.47(t,2H),4.96(s,2H),6.99-7.04(m,4H),7.16(d,2H),7.34(d,2H),7.79(d,2H),7.95(d,2H),8.73(s,1H);EIMSm/z=622[M +]。
Embodiment 50: the preparation of the bromo-3-of (E)-1-benzyl-5-((E)-(4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) α-tolylene) hydrazone group) indole-2-ketone (48)
Preparation method is with embodiment three, and just isatin replaces 1-benzyl-5-bromoisatin, yield 60%. 1HNMR(d 6-DMSO,400MHz)δ:2.56(s,3H),4.48(t,2H),4.77(t,2H),4.98(s,2H),7.00(d,1H),7.16(d,2H),7.27-7.29(m,1H),7.33-7.36(m,3H),7.63(dd,1H),7.94(d,2H),8.06(s,1H),8.18(d,1H),8.72(s,1H);EIMSm/z=588[M +]。
Embodiment 51: the compound that embodiment prepares measures the inhibit activities of various bacteria:
Minimum inhibitory concentration method is adopted to carry out Antibacterial Activity to streptococcus aureus, Clostridium perfringens, Candida albicans, intestinal bacteria.The concrete operations of minimum inhibitory concentration method are: be dissolved in by the compound of certain mass in appropriate dimethyl sulfoxide (DMSO), and ultrasonic or heating makes it fully dissolve or disperse, and is made into certain density compound solution; Then stepwise dilution, obtains the solution to be measured of a series of concentration gradient.Adopt 96 orifice plates to measure, in every hole, add 190 μ L containing germy nutrient solution, then in every hole, add the bacterium liquid to be measured of 10 μ L different concns, be placed in 37 ocultivate 24h in C constant incubator, taking out and observe whether have colony growth, is the minimum inhibitory concentration MIC of this antiseptic-germicide not have the lowest concentration of drug of bacterial growth.
Active height represents with minimum inhibitory concentration MIC, and MIC is less, and the activity of this compound is higher, and anti-microbial activity is better, the results are shown in Table 1.
The bacteriostatic activity test result of table 1. metronidazole-isatin type compound.
Metronidazole as can be seen from Table 1-isatin type compound has anti-microbial activity in various degree, and wherein compound 2,6,10,18,26,31,36,37,46,47,48 pairs of streptococcus aureuses, Clostridium perfringens, Candida albicans, intestinal bacteria all have good inhibit activities.
Above-mentioned just preferred embodiment of the present invention, not does any pro forma restriction to the present invention.Any those of ordinary skill in the art, when not departing from technical solution of the present invention scope, can utilize the technology contents of above-mentioned announcement to make many possible variations and modification to technical solution of the present invention, or being revised as the Equivalent embodiments of equivalent variations.Therefore, every content not departing from technical solution of the present invention, according to the technology of the present invention essence to any simple modification made for any of the above embodiments, equivalent variations and modification, all should drop in the scope of technical solution of the present invention protection.

Claims (3)

1. metronidazole-isatin type compound, is characterized in that: this compound has structure as shown in the formula (I):
（I）
Wherein: R 1for hydrogen, alkyl, benzyl or substituted benzyl, R 2, R 3, R 4or R 5for hydrogen, fluorine, chlorine, bromine, alkyl, alkoxyl group or nitro.
2. a preparation method for metronidazole-isatin type compound, is characterized in that comprising following step:
Step 1: metronidazole, pyridine, Tosyl chloride are placed in round-bottomed flask, stirred at ambient temperature reaction 8-20h, reaction solution is poured in suitable quantity of water, crystallize out, suction filtration, uses suitable quantity of water washing leaching cake, dries, obtain pressed powder 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester, described metronidazole, the mol ratio of Tosyl chloride are 1:(1 ~ 10);
Step 2: p-Hydroxybenzaldehyde, cesium carbonate, 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester are placed in round-bottomed flask, add N, dinethylformamide, be warming up to 50-100 DEG C of reaction 5-24h, add water, extraction into ethyl acetate, merge organic phase, cross silica gel chromatography, obtain solid 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde; The mol ratio of described p-Hydroxybenzaldehyde, 2-(2-methyl-5-nitro-1H-imidazoles-1-base) ethyl 4-toluene sulfonic acide ester, cesium carbonate is 1:(1 ~ 4): (1 ~ 5);
Step 3: replacement isatin, hydrazine hydrate are placed in round-bottomed flask, add methyl alcohol, back flow reaction 3-8h, stopped reaction, cool to room temperature, by reaction solution suction filtration, uses proper amount of methanol washing leaching cake, dries, and obtains pressed powder and replaces 3-hydrazono-indole-2-ketone; Described replacement isatin, the mol ratio of hydrazine hydrate are 1:(1 ~ 4);
Step 4: 3-hydrazono-indole-2-ketone will be replaced, 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde, glacial acetic acid be placed in round-bottomed flask, add ethanol, temperature rising reflux, reaction 2-10h, stopped reaction, after cool to room temperature, suction filtration, use ethanol in proper amount washing leaching cake, obtain thick product, obtain pressed powder metronidazole-isatin type compound (I) through purification by silica gel column chromatography; The mol ratio of described replacement 3-hydrazono-indole-2-ketone, 4-(2-(2-methyl-5-nitro-1H-imidazoles-1-base) oxyethyl group) phenyl aldehyde is 1:(1 ~ 5).
3. the application of metronidazole according to claim 1-isatin type compound in preparation antibacterials.
CN201610080048.7A 2016-02-04 2016-02-04 Metronidazole-isatin type compound as well as preparation method and application thereof Pending CN105541808A (en)

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