CN102633717B - N-acetyl-quinoline-2 (1H) ketone compounds as well as preparation method and application thereof - Google Patents

N-acetyl-quinoline-2 (1H) ketone compounds as well as preparation method and application thereof Download PDF

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CN102633717B
CN102633717B CN2012100896091A CN201210089609A CN102633717B CN 102633717 B CN102633717 B CN 102633717B CN 2012100896091 A CN2012100896091 A CN 2012100896091A CN 201210089609 A CN201210089609 A CN 201210089609A CN 102633717 B CN102633717 B CN 102633717B
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quinoline
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吉庆刚
刘洪彬
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Southwest University
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Abstract

The invention discloses N-acetyl-quinoline-2 (1H) ketone compounds shown in a general formula I or II and pharmaceutical salts thereof. In the general formula I, R1 and R2 are independently hydrogen, C1-C6 alkyl, phenyl-substituted C1-C6 alkyl or hydroxyl-substituted C1-C6 alkyl; and in the general formula II, Het is 1-hexahydropiperidinyl, 1-tetrahydropyrrolyl, 1-morpholinyl, 1-piperazinyl, N-Boc (t-butyloxy carbonyl)-piperazinyl, 1-imidazolyl or 1-benzimidazolyl. The compounds show a certain inhibition activity on bacteria and fungi including methicillin-resistant staphylococcus aureus, partial compounds show good anti-bacteria effect on all tested bacteria and fungi, and the anti-bacteria activity and anti-fungus activity of the compounds are basically equivalent with those of streptomycin and fluconazole; and partial compounds show good inhibition activity on partial strains, and the antibacterial effect of the compounds is stronger than that of streptomycin or fluconazole. The N-acetyl-quinoline-2 (1H) ketone compounds and the pharmaceutical salts thereof are simple in preparation method and can be used for preparing anti-bacteria and/or anti-fungus medicaments.

Description

N-acetyl-quinoline-2 (1H) ketone compounds and its preparation method and application
Technical field
The invention belongs to chemical field, relate to a kind of novel quinoline ketone compounds, also relate to the preparation method of this compound, and the application in pharmacy field.
Background technology
Quinolone and derivative thereof are class medicines of synthetic, and its activity at aspects such as antibacterium, antimycotic, antitumor, antiviral, anxiety, xitix has caused people's extensive attention.Since the fixed acid of first quinolones naphthalene in 1962 occurs, scientist in succession develop four generation quinolones, be widely used at present clinically, be used for prevention and treatment various bacteria and mycoplasma disease.But along with the life-time service of quinolones, the resistance of bacterium and fungi etc. is also at rapid growth.Therefore, need continual exploitation to have the quinolones of the novel texture of similar or stronger activity.
Summary of the invention
In view of this, one of purpose of the present invention is to provide a kind of quinolinones compound of novel texture, and this compound is compared with existing antibacterials, has similar or stronger anti-microbial activity; Two of purpose is to provide the preparation method of described quinolinones compound; Three of purpose is to provide the application of described quinolinones compound in pharmacy field.
, for achieving the above object, the invention provides following technical scheme:
1. general formula IOr IIShown N-acetyl-quinoline-2 (1H) ketone compounds and pharmacologically acceptable salt thereof:
Figure 2012100896091100002DEST_PATH_IMAGE001
General formula IIn, R 1And R 2Be the C1-C6 alkyl of hydrogen, C1-C6 alkyl, phenyl substituted or the C1-C6 alkyl that hydroxyl replaces independently; General formula IIIn, Het is 1-six hydrogen piperidyls, 1-Pyrrolidine base, 1-morpholinyl, 1-piperazinyl, N-Boc-piperazinyl, 1-imidazolyl or 1-benzimidazolyl-.
Further, general formula IIn, R 1And R 2Be hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, benzyl or hydroxyethyl independently.
Further, general formula IIn, R 1And R 2Be hydrogen, ethyl, n-propyl, the tertiary butyl, benzyl or hydroxyethyl independently.
Further, general formula IShown N-acetyl-quinoline-2 (1H) ketone compounds is any in following compound:
Compound Ia: R 1For n-propyl, R 2For n-propyl;
Compound Ib: R 1For ethyl, R 2For ethyl;
Compound Ic: R 1For hydrogen, R 2For the tertiary butyl;
Compound Id: R 1For benzyl, R 2For benzyl;
Compound Ie: R 1For hydroxyethyl, R 2For hydroxyethyl;
Compound If: R 1For hydrogen, R 2For benzyl.
Further, the pharmacologically acceptable salt of described N-acetyl-quinoline-2 (1H) ketone compounds is hydrochloride.
2. the preparation method of described N-acetyl-quinoline-2 (1H) ketone compounds and pharmacologically acceptable salt thereof comprises the following steps:
A. with formula IVShown in the reaction in organic solvent, under alkaline condition of compound and chloroacetyl chloride make intermediate V
B. with intermediate VWith aminated compounds HNR 1R 2Or nitrogen-containing heterocycle compound HetH reaction in organic solvent, under alkaline condition, catalyst makes general formula IOr IIShown N-acetyl-quinoline-2 (1H) ketone compounds;
C. with general formula IOr IIShown N-acetyl-quinoline-2 (1H) ketone compounds and pharmaceutically acceptable acid HZ react and make general formula in organic solvent IIIOr VIThe pharmacologically acceptable salt of shown N-acetyl-quinoline-2 (1H) ketone compounds;
Chemical equation is as follows:
R in formula 1, R 2With the definition of Het as previously mentioned.
Further, in described step a, organic solvent is methylene dichloride, and alkali is triethylamine, formula IVShown in the molar ratio of compound and chloroacetyl chloride be 1:1.1; In described step b, organic solvent is ethanol, and alkali is sodium bicarbonate, and catalyzer is potassiumiodide, intermediate VWith aminated compounds HNR 1R 2Or the molar ratio of nitrogen-containing heterocycle compound HetH is 1:1.05; In described step c, pharmaceutically acceptable acid is hydrochloric acid, and organic solvent is methyl alcohol, general formula IOr IIShown N-acetyl-quinoline-2 (1H) ketone compounds and the molar ratio of concentrated hydrochloric acid are 1:1.2.
3. described N-acetyl-quinoline-2 (1H) ketone compounds and pharmacologically acceptable salt thereof the application in preparation antibacterium and/or antifungal drug.
Further, described bacterium is any one or more in methicillin-resistant staphylococcus aureus, streptococcus aureus, Bacillus subtilus, intestinal bacteria and Bacillus proteus, and described fungi is candidiasis and/or Candida albicans.
Beneficial effect of the present invention is: the quinolinones compound that the invention discloses a kind of novel texture---N-acetyl-quinoline-2 (1H) ketone compounds and pharmacologically acceptable salt thereof, these compounds comprise that to bacterium and fungi methicillin-resistant staphylococcus aureus all shows certain inhibition activity, wherein compound VIbAll bacteria tested and fungi are all shown good fungistatic effect, and antibacterial activity and Streptomycin sulphate are substantially suitable, and anti-mycotic activity and fluconazole are substantially suitable; Part of compounds shows good inhibition activity to some bacterial classification, as compound IIIaTo streptococcus aureus, compound VIaTo Bacillus subtilus, compound IIIbTo intestinal bacteria, compound VIeTo Bacillus proteus and candidiasis, compound IIIeInhibition to Candida albicans all obviously is better than control drug Streptomycin sulphate or fluconazole; The preparation method of N-acetyl-quinoline-2 (1H) ketone compounds of the present invention and pharmacologically acceptable salt thereof is simple, can separately or with other, have the compatibilities such as bioactive compound and/or extract, again with pharmaceutically acceptable carrier combinations, make folk prescription or Compound Resisting bacterium and/or antimycotic medicine of various formulations, can provide how efficient, safe drug candidate for the clinical treatment that catches, meet many-sided demand of clinical treatment.
Embodiment
, in order to make the purpose, technical solutions and advantages of the present invention clearer, below will be described in detail the preferred embodiments of the present invention.
The compound that makes in preferred embodiment is measured fusing point (proofreading and correct) with the accurate micro melting point apparatus of X-6, with BrukerAv-300 type fourier transform NMR instrument measure hydrogen nuclear magnetic resonance ( 1HNMR) spectrum, measure ESI-MS (m/z) spectrum with HTC liquid chromatography mass combined instrument.
The preparation of embodiment 1,2-chloro-N-(1,2,3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) ethanamide (V)
Figure 529045DEST_PATH_IMAGE001
Add 5-quinolylamine-2 (1H) ketone 1g(6.2mmol in reaction flask), triethylamine 0.69g(6.8mmol) and methylene dichloride 15ml, stir, the lower chloroacetyl chloride 0.77g(6.8mmol that drips of room temperature (25 ℃)), dropwise rear continuation stirring reaction, reaction in 4 hours is complete, boil off solvent, residue is poured in the 20ml frozen water, suction filtration, drying, obtain brown solid 1.1g, productive rate 75%, confirm as 2-chloro-N-(1,2 through structural characterization, 3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) ethanamide.mp:153.1-154℃;? 1HNMR?(300?MHz?,?DMSO-d6):?2.400?(t,?J=7.5Hz,?2H),?2.734?(t,?J=7.5Hz,?2H),?4.288?(s,?2H,?CH2),?6.740?(d,?J=3.9Hz,?1H),?6.982?(d,?J=3.9Hz,?1H),?7.125?(t,?J=7.8Hz,?1H),?9.825?(s,?1H),?10.130?(s,?1H).
The preparation of embodiment 2,2-substituted-amino-N-(1,2,3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) acetamide hydrochloride (III)
Add ethanol 20ml, 2-chloro-N-(1 in reaction flask, 2,3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) ethanamide 0.2g(0.84 mmol) and potassiumiodide 0.153g(0.88mmol), be heated with stirring to 85 ℃ of back flow reaction 30 minutes, add successively again sodium bicarbonate 0.085g(0.92mmol) and amine (0.88mmol), back flow reaction continued, with tlc monitoring reaction process.Reaction in X hour is complete, cooling, suction filtration, and filtrate steaming removal solvent, the residue recrystallization, obtain general formula IShown in compound.With general formula IShown in compound dissolution in methanol solution, press general formula IShown in the molar ratio of compound and concentrated hydrochloric acid be that 1:1.2 splashes into concentrated hydrochloric acid, room temperature (25 ℃) stirring reaction 1 hour, steaming desolventizes, residue ether recrystallization, obtain general formula IIIShown in compound.Concrete experiment condition and the results are shown in Table 1.
The preparation of table 1 2-substituted-amino-N-(1,2,3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) acetamide hydrochloride
Figure DEST_PATH_IMAGE006
Compound IIIa: mp:211.6-213.1 ℃; ESI-MS:304[M] +; 1HNMR (300 MHz, DMSO-d6): 0.860 (t, J=7.2Hz, 6H); (1.405-1.528 m, 4H); (2.438 t, J=7.2Hz, 2H); (2.493 t, J=7.2Hz, 4H), 2.737 (t, J=7.2Hz, 2H), 3.156 (s, 2H), (6.671 d, J=7.8Hz, 1H), 7.106 (t, J=7.2Hz, 1H), 7.348 (d, J=7.5Hz, 1H), 9.391 (s, 1H), 10.125 (s, 1H).
Compound IIIb: mp:129.2-131 ℃; ESI-MS:276[M] +; 1HNMR (300 MHz, DMSO-d6): 1.038 (t, J=7.2Hz, 6H), 2.448 (t, J=7.5Hz, 2H), 2.586-2.653 (m, 4H), 2.747 (t, J=7.2Hz, 2H), 3.166 (s, 2H), 6.673 (d, J=7.2Hz, 1H), 7.107 (t, J=7.8Hz, 1H), 7.336 (d, J=7.8Hz, 1H), (9.523 s, 1H), 10.126 (s, 1H).
Compound IIIc: mp:271.6-273.5 ℃; ESI-MS:276 [M] +; 1HNMR (300 MHz, D 2O): 1.267 (s, 9H), 2.439 (t, J=7.2Hz, 2H), 2.693 (t, J=7.2Hz, 2H), 3.949 (s, 2H), (6.767 d, J=7.8Hz, 1H), (6.886 d, J=7.8Hz, 1H), (7.131 t, J=7.8Hz, 1H).
Compound IIId: mp:139.9-140.8 ℃; ESI-MS:400[M] +; 1HNMR (300 MHz, DMSO-d6): 2.340 (t, J=7.5Hz, 2H), 2.534 (t, J=7.2Hz, 2H), 4.147 (s, 2H), 6.709 (d, J=7.5Hz, 1H), 6.795 (d, J=7.5Hz, 1H), 7.082 (t, J=8.1Hz, 1H), (7.416-7.453 m, 8H), 7.520-7.521 (m, 2H), (9.584 s, 1H), 10.145 (s, 1H).
Compound IIIe: mp:187.7-188.6 ℃; ESI-MS:308[M] +; 1HNMR (300 MHz, D 2O): 2.441 (t, J=7.5Hz, 2H), 2.705 (t, J=7.8Hz, 2H), 3.434 (t, J=5.1Hz, 4H), 3.845 (t, J=4.8Hz, 4H), (4.331 s, 2H), 6.774 (d, J=8.1Hz, 1H), 6.901 (d, J=7.5Hz, 1H), (7.141 t, J=7.8Hz, 1H).
Compound IIIf: mp:164.2-165.4 ℃; ESI-MS:308[M] +; 1HNMR (300 MHz, DMSO-d6): 2.394 (t, J=7.5Hz, 2H), 2.707 (t, J=7.5Hz, 2H), 3.262 (s, 2H), (3.446 s, 1H), 3.748 (s, 1H), 6.674 (d, J=6.6Hz, 1H), 6.818 (t, J=7.2Hz, 1H), 7.108 (d, J=7.5Hz, 1H), 7.202-7.380 (m, 5H), 9.570 (s, 1H), 10.120 (s, 1H).
The preparation of embodiment 3,2-substituted nitrogen-containing heterocyclic base-N-(1,2,3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) acetamide hydrochloride (VI)
Figure 77893DEST_PATH_IMAGE003
Add ethanol 25ml, 2-chloro-N-(1 in reaction flask, 2,3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) ethanamide 0.239g(1mmol) and potassiumiodide 0.183g(1.05mmol), be heated with stirring to 85 ℃ of back flow reaction 30 minutes, add successively again sodium bicarbonate 0.088g(1.1mmol) and HetH(1.05mmol), continue back flow reaction, with tlc monitoring reaction process.React complete after, cooling, suction filtration, filtrate steaming removal solvent, residue are general formula IIShown in compound.With general formula IIShown in compound dissolution in methanol solution, press general formula IIShown in the molar ratio of compound and concentrated hydrochloric acid be that 1:1.2 splashes into concentrated hydrochloric acid, room temperature (25 ℃) stirring reaction 1 hour, steaming desolventizes, residue, with ether-alcohol mixed solvent recrystallization, obtains general formula VIShown in compound.Concrete experiment condition and the results are shown in Table 2.
The preparation of table 2 2-substituted nitrogen-containing heterocyclic base-N-(1,2,3,4-tetrahydrochysene-2-carbonyl quinoline-5-yl) acetamide hydrochloride
Figure 2012100896091100002DEST_PATH_IMAGE004
Compound VIa: mp:275.2-276.4 ℃; ESI-MS:289[M] +; 1HNMR (300 MHz, D 2O): 2.435 (t, J=7.2Hz, 2H); (2.674 t, J=7.2Hz, 2H), 2.785 (d, J=4.5Hz, 4H), 3.189 (t, J=4.5Hz, 4H), 3.275 (s, 2H), (6.766 d, J=7.8Hz, 1H), (6.853 d, J=7.5Hz, 1H), (7.125 t, J=7.5Hz, 1H).
Compound VIb: mp:207.6-209 ℃; ESI-MS:271[M] +; 1HNMR (300 MHz, DMSO-d6): 2.401 (t, J=7.8Hz, 2H), 2.758 (t, J=7.8Hz, 2H), 4.923 (s, 2H), 6.715 (d, J=7.2Hz, 1H), 6.892 (s, 1H), 7.018 (d, J=7.5Hz, 1H), 7.111 (t, J=7.2Hz, 1H), (7.166 s, 1H), 7.640 (s, 1H), (9.820 s, 1H), 10.142 (s, 1H).
Compound VIc: mp:181.9-183.7 ℃; ESI-MS:300[M] +; 1HNMR (300 MHz, DMSO-d6): 2.426 (t, J=7.2Hz, 2H), 2.530 (t, J=7.2Hz, 4H), 2.742 (t, J=4.2Hz, 2H), (3.123 s, 2H), 3.644 (t, J=4.5Hz, 4H), (6.691 d, J=8.1Hz, 1H), 7.104 (t, J=7.5Hz, 1H), 7.196 (d, J=7.2Hz, 1H), (9.456 s, 1H), 10.116 (s, 1H).
Compound VId: mp:〉300 ℃; ESI-MS:321[M] +; 1HNMR (300 MHz, DMSO-d6): 2.411 (t, J=7.8Hz, 2H), (2.794 t, J=7.2Hz, 2H), 5.208 (s, 2H), 6.716 (d, J=7.2Hz, 1H), 7.03 (d, J=7.2Hz, 1H), 7.105 (t, J=7.2Hz, 1H), 7.183-7.295 (m, 2H), (7.547 d, J=7.5Hz, 1H), (7.665 d, J=7.2Hz, 1H), (8.235 s, 1H), 9.986 (s, 1H), 10.144 (s, 1H).
Compound VIe: mp:180.7-182.5 ℃; ESI-MS:288[M] +; 1HNMR 300 MHz, DMSO-d6): 1.784 (s, 4H), (2.401 t, J=7.5Hz, 2H), (2.782 t, J=7.5Hz, 2H), (3.069 s, 2H), 3.433-3.471 (m, 2H), 4.169-4.180 (m, 2H), (6.769 d, J=7.2Hz, 1H), (7.001 d, J=7.2Hz, 1H), (7.144 t, J=7.8Hz, 1H), 10.193 (s, 1H), 10.459 (s, 1H).
Compound VIf: mp:176.8-178.5 ℃; ESI-MS:274[M] +; 1HNMR (300 MHz, DMSO-d6): 1.752 (s, 4H), 2.413 (t, J=7.2Hz, 2H), 2.617 (s, 4H), 2.713 (t, J=7.2Hz, 2H), 3.240 (s, 4H), 6.688 (d, J=7.2Hz, 1H), 7.082 (d, J=7.5Hz, 1H), 7.141 (t, J=7.2Hz, 1H), (9.417 s, 1H), 10.104 (s, 1H).
Compound VIg: mp:211.2-212.5 ℃; ESI-MS:389[M] +; 1HNMR (300 MHz, DMSO-d6): 1.394 (s, 9H), (2.420 t, J=7.5Hz, 2H), (2.469-2.497 m, 4H), 2.735 (t, J=7.2Hz, 2H), 3.379-3.411 (m, 4H), 3.144 (s, 2H), (6.688 d, J=7.2Hz, 1H), (7.102 t, J=8.4Hz, 1H), (7.194 d, J=8.4Hz, 1H), 9.447 (s, 1H), 10.123 (s, 1H).
The antimicrobial acivity of embodiment 4, part N-acetyl-quinoline-2 of the present invention (1H) ketone compounds
N-acetyl-quinoline-2 (1H) ketone compounds that embodiment 2-3 is made dissolves and makes the solution that concentration is 512 μ g/mL with distilled water respectively, dilute with water is made concentration and is respectively the gradient dilution liquid of 256,128,64,32,16,8,4,2,1 μ g/mL again, adopt disk diffusion method to measure the antimicrobial acivity of compound, 37 ℃ of cultivations of temperature 24 hours, measure minimum inhibitory concentration (MIC), use clinical anti-bacterial drug Streptomycin sulphate and fluconazole as antifungal medicine simultaneously as positive control, the results are shown in Table 3.
The MIC(ug/ml of table 3 part N-acetyl-quinoline-2 of the present invention (1H) ketone compounds)
Figure DEST_PATH_IMAGE012
As can be seen from Table 3, compound IIIa~ IIIfWith VIa~ VIgBacterium and fungi are all shown certain inhibition activity, wherein compound VIbAll bacteria tested and fungi are all shown good fungistatic effect, and antibacterial activity and Streptomycin sulphate are substantially suitable, and anti-mycotic activity and fluconazole are substantially suitable; Part of compounds shows good inhibition activity to some bacterial classification, as compound IIIaTo streptococcus aureus, compound VIaTo Bacillus subtilus, compound IIIbTo intestinal bacteria, compound VIeTo Bacillus proteus and candidiasis, compound IIIeInhibition to Candida albicans all obviously is better than control drug Streptomycin sulphate or fluconazole; Methicillin-resistant staphylococcus aureus is to Streptomycin sulphate resistance, but compound IIIa~ IIIeWith VIa~ VIgIt is all shown fungistatic effect preferably.
Explanation is finally, above embodiment is only unrestricted in order to technical scheme of the present invention to be described, although by invention has been described with reference to the preferred embodiments of the present invention, but those of ordinary skill in the art is to be understood that, can make various changes to it in the form and details, and not depart from the spirit and scope of the present invention that appended claims limits.

Claims (9)

1. N-acetyl-quinoline-2 (1H) ketone compounds and the pharmacologically acceptable salt thereof shown in general formula I or II:
In general formula I, R 1And R 2Be the C1-C6 alkyl of hydrogen, C1-C6 alkyl, phenyl substituted or the C1-C6 alkyl that hydroxyl replaces independently, but R 1And R 2Be not hydrogen simultaneously; In general formula I I, Het is 1-six hydrogen piperidyls, 1-Pyrrolidine base, 1-morpholinyl, 1-piperazinyl, N-Boc-piperazinyl, 1-imidazolyl or 1-benzimidazolyl-.
2. N-acetyl-quinoline-2 (1H) ketone compounds according to claim 1 and pharmacologically acceptable salt thereof, is characterized in that, in general formula I, and R 1And R 2Be hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, benzyl or hydroxyethyl independently.
3. N-acetyl-quinoline-2 (1H) ketone compounds according to claim 2 and pharmacologically acceptable salt thereof, is characterized in that, in general formula I, and R 1And R 2Be hydrogen, ethyl, n-propyl, the tertiary butyl, benzyl or hydroxyethyl independently.
4. N-acetyl-quinoline-2 (1H) ketone compounds according to claim 3 and pharmacologically acceptable salt thereof, is characterized in that, N-acetyl-quinoline-2 (1H) ketone compounds shown in general formula I is any in following compound:
Compound I a:R 1For n-propyl, R 2For n-propyl;
Compounds ib: R 1For ethyl, R 2For ethyl;
Compound I c:R 1For hydrogen, R 2For the tertiary butyl;
Compound I d:R 1For benzyl, R 2For benzyl;
Compound I e:R 1For hydroxyethyl, R 2For hydroxyethyl;
Compound I f:R 1For hydrogen, R 2For benzyl.
5. described N-acetyl-quinoline-2 (1H) ketone compounds of according to claim 1 to 4 any one and pharmacologically acceptable salt thereof, is characterized in that, described pharmacologically acceptable salt is hydrochloride.
6. the preparation method of described N-acetyl-quinoline-2 (1H) ketone compounds of claim 1 to 5 any one and pharmacologically acceptable salt thereof, is characterized in that, comprises the following steps:
A. with compound shown in formula IV and chloroacetyl chloride in organic solvent, reaction makes intermediate V under alkaline condition;
B. with intermediate V and aminated compounds HNR 1R 2Or nitrogen-containing heterocycle compound HetH reaction in organic solvent, under alkaline condition, catalyst makes N-acetyl-quinoline-2 (1H) ketone compounds shown in general formula I or II;
C. N-acetyl-quinoline-2 (1H) ketone compounds shown in general formula I or II and pharmaceutically acceptable acid HZ are reacted in organic solvent the pharmacologically acceptable salt of N-acetyl-quinoline-2 (1H) ketone compounds that makes shown in general formula III or VI;
Chemical equation is as follows:
Figure FDA0000356085762
R in formula 1, R 2Identical with definition described in claim 1 with the definition of Het.
7. the preparation method of N-acetyl-quinoline-2 (1H) ketone compounds according to claim 6 and pharmacologically acceptable salt thereof, it is characterized in that, in described step a, organic solvent is methylene dichloride, and alkali is triethylamine, and the molar ratio of compound shown in formula IV and chloroacetyl chloride is 1:1.1; In described step b, organic solvent is ethanol, and alkali is sodium bicarbonate, and catalyzer is potassiumiodide, intermediate V and aminated compounds HNR 1R 2Or the molar ratio of nitrogen-containing heterocycle compound HetH is 1:1.05; In described step c, pharmaceutically acceptable acid is hydrochloric acid, and organic solvent is methyl alcohol, and the molar ratio of N-acetyl-quinoline-2 (1H) ketone compounds shown in general formula I or II and concentrated hydrochloric acid is 1:1.2.
8. described N-acetyl-quinoline-2 (1H) ketone compounds of claim 1 to 5 any one and pharmacologically acceptable salt thereof the application in preparation antibacterium and/or antifungal drug.
9. application according to claim 8, is characterized in that, described bacterium is any one or more in streptococcus aureus, Bacillus subtilus, intestinal bacteria and Bacillus proteus, and described fungi is candidiasis and/or Candida albicans.
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