CN104072501B - One treats colpitic compound and application thereof - Google Patents
One treats colpitic compound and application thereof Download PDFInfo
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- CN104072501B CN104072501B CN201410333552.4A CN201410333552A CN104072501B CN 104072501 B CN104072501 B CN 104072501B CN 201410333552 A CN201410333552 A CN 201410333552A CN 104072501 B CN104072501 B CN 104072501B
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 10
- 210000001215 vagina Anatomy 0.000 claims description 10
- 241000588724 Escherichia coli Species 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 abstract description 9
- 206010046914 Vaginal infection Diseases 0.000 abstract description 6
- 201000008100 Vaginitis Diseases 0.000 abstract description 4
- 239000002547 new drug Substances 0.000 abstract description 2
- 230000000452 restraining effect Effects 0.000 abstract description 2
- 239000007787 solid Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 9
- 238000000967 suction filtration Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 241000588747 Klebsiella pneumoniae Species 0.000 description 5
- 241000191992 Peptostreptococcus Species 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 241000943303 Enterococcus faecalis ATCC 29212 Species 0.000 description 4
- 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000751182 Staphylococcus epidermidis ATCC 12228 Species 0.000 description 4
- -1 bromo-1-cyclopropyl Chemical group 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 150000002475 indoles Chemical class 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 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 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 229960003328 benzoyl peroxide Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000000050 nutritive effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- ZTVIKZXZYLEVOL-DGKWVBSXSA-N 2-hydroxy-2-phenylacetic acid [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] ester Chemical group C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-DGKWVBSXSA-N 0.000 description 1
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 241000191963 Staphylococcus epidermidis Species 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to one and treat colpitic compound and application thereof, described compound has having structure:
wherein, the arbitrary integer in n=2-6; R
1=3-Cl, 4-F; 4-CBr
3; Or 3,4-bis--Br;
or
Description
Technical field
The present invention relates to field of medicaments, relate in particular to one and treat colpitic compound and application thereof.
Background technology
Vaginitis and colpitis.Normal healthy women vagina has nature defense function due to the intrusion of feature to pathogenic agent of anatomical tissue.As closing of vaginal tract, vagina front and rear wall is close to, the hyperplasia of vaginal epithelial cell under estrogenic impact and cells of superficial layer angling, vagina acid-base degree keeps balance, the breeding of the pathogenic agent of adaptation alkalescence is suppressed, and neck tube mucus is in alkalescence, when the natural defense function of vagina is damaged, pathogenic agent is easy to invade, and causes colpitis.At present, from the secretory product of vaginitis patient, the pathogenic bacterium such as escherichia coli ATCC25922, Klebsiella Pneumoniae ATCC700603, enterococcus faecalis ATCC29212, peptostreptococcus ATCC10149, staphylococcus epidermidis ATCC12228 are isolated.Therefore, find and for these pathogenic bacterium, there is good inhibiting medicine and just become the colpitic key of clinical treatment.
Summary of the invention
The object of this invention is to provide one and treat colpitic compound.
The present invention also aims to the application that this compound is provided.
In order to realize object of the present invention, the invention provides one and treat colpitic compound, described compound has having structure:
Wherein, the arbitrary integer in n=2-6;
R
1=3-Cl, 4-F; 4-CBr
3; Or 3,4-bis--Br;
or
Preferably, n=3.
Preferably, R
1=3-Cl, 4-F.
Preferably,
The present invention also provides above-claimed cpd to suppress the application in the medicine of vagina escherichia coli in preparation.
The present invention also provides above-claimed cpd to suppress the application in the medicine of vagina Klebsiella Pneumoniae in preparation.
The present invention also provides above-claimed cpd to suppress the application in the medicine of vagina enterococcus faecalis in preparation.
The present invention also provides above-claimed cpd to suppress the application in the medicine of vagina peptostreptococcus in preparation.
The present invention also provides above-claimed cpd to suppress the application in the medicine of vagina staphylococcus epidermidis in preparation.
Preferably, described compound can make various formulation together with pharmaceutically acceptable carrier.
" the treatment significant quantity " of compound of the present invention be one when giving treatment experimenter in need, improve the amount of the prognosis of this experimenter, such as, be delayed the outbreak of one or more symptoms relevant to bacteriological infection of this experimenter and/or reduce its seriousness.The amount of the compound of this disclosure of experimenter to be administrated is had to depend on the feature of concrete disease, administering mode and experimenter, such as general health, other diseases, age, sex, genotype, body weight and the tolerance to medicine.Technician can depend on these and other because usually determining suitable dosage.
These compounds can be tested to determine the concentration of the compound had required for a kind of given pharmacological effect in one of some biological assays.
In order to prepare pharmaceutical composition of the present invention, the particular compound of significant quantity closely mixed as the pharmaceutically acceptable carrier of activeconstituents and at least one, this carrier depends on that the dosage form desired by administration can adopt various ways.These pharmaceutical compositions are in the unit dosage being suitable for, being preferably suitable for intravaginal administration.
Such as, be suitable in the composition of intravaginal administration in preparation, any common drug medium can be adopted, such as, as water, glycols, oils, alcohols etc.
Compound of the present invention has obvious restraining effect for bacterial strain common in vaginitis, therefore has great importance clinically, is expected to be developed to the effectively colpitic new drug for the treatment of.
Embodiment
The present invention is further illustrated below by embodiment.It should be understood that embodiments of the invention are for illustration of the present invention instead of limitation of the present invention.Essence according to the present invention all belongs to the scope of protection of present invention to the simple modifications that the present invention carries out.Unless otherwise stated, the percentage ratio in the present invention is weight percentage.
Embodiment 1
Melting point compound adopts capillary tube technique to measure, and temperature is not calibrated; Proton nmr spectra BrukerARX-300 measures; Mass spectrum adopts Agilent1100LCIMS to measure; Agents useful for same is analytical pure or chemical pure.
The first step:
The preparation of the bromo-1-cyclopropyl of 5-acetoxyl group-6--3-ethoxycarbonyl-1H-indoles-2-picoline hydrobromate (2)
5-acetoxyl group-6-bromo-2-brooethyl-1-cyclopropyl-1H-Indole-3-Carboxylic Acid's ethyl ester 45.9g (0.1mol) is added in chloroform 200mL, is heated to dissolve.Drip pyridine 11.9g (0.15mol), drip and finish, back flow reaction 30min.Cooling, suction filtration, ether 30mL washs, dry, obtains white solid 51.0g, yield: 94.8%, m.p.234-236 DEG C, MS [MH
+] (m/z): 457.3,459.3.
Second step
The preparation of 4-nitroso-group-DMA hydrochloride
200mL concentrated hydrochloric acid is added three-necked bottle, in three-necked bottle, drips DMA 63mL (0.50mol).Under cryosel bath mechanical stirring, in three-necked bottle, drip the 60mL aqueous solution (being added drop-wise to below liquid level) of Sodium Nitrite 36g (0.52mol), maintain the temperature at less than 10 DEG C.After dripping off, then stir 10 to 20min; Leave standstill 1 hour, suction filtration, concentrated hydrochloric acid-water (1: 1) washs, a small amount of washing with alcohol, dry.Obtain yellow solid 67.5g.Yield: 90.0%.
3rd step
The preparation of the bromo-1-cyclopropyl of 6--2-formyl radical-5-hydroxyl-1H-indoles-3 carboxylic acid, ethyl ester (3)
Compound 248.4g (0.09mol) and freshly prepd 4-nitroso-group-DMA 16.8g (0.09mol) is added in ethanol 250mL, stirs the aqueous sodium hydroxide solution 80mL of lower dropping 13.5% (w/w).Drip and finish, stirring at room temperature 24h.Suction filtration, washing, obtains yellow solid.Be placed in beaker, add water 20mL, the lower vitriol oil that drips of cooling adjusts pH to be 1, and 20min is stirred in continuation, suction filtration, washing, dry, obtains faint yellow solid 327.7g, yield: 87.4%, m.p.240-242 DEG C.
4th step
The preparation of the bromo-1-cyclopropyl of 6--2-formyl radical-5-(3-chlorine propoxy-)-1H-indoles-3 carboxylic acid, ethyl ester (4a)
Compound 321.1g (0.06mol), Anhydrous potassium carbonate 12.4g (0.09mol) are added in DMF 100mL, is heated to 80 DEG C.Drip 1,3-bromo-chloropropane 14.2g (0.09mol), reaction 2h.Reaction solution is poured in frozen water, separate out a large amount of solid.Suction filtration, washing, dry, obtain yellow solid 4a23.0g, yield: 89.5%, m.p.137-139 DEG C.
5th step
The preparation of the bromo-8-of 7-(3-chlorine propoxy-)-5-cyclopropyl-1,2-dihydro-5H-pyridazine also [4,5-b] indoles-1-ketone (5a)
By compound 4a0.05mol, the hydrazine hydrate solution 3.0mL (0.05mol) of 80% (w/w) adds in Glacial acetic acid 50mL, is heated to 85 DEG C, stirring reaction 1h, then adds hydrazine hydrate 3.0mL (0.05mol) and react 1h.Cooling, suction filtration, ethanol 20mL washs, dry, obtains white solid 5a16.8g, yield: 84.8%, m.p.221-223 DEG C, MS [M+Na
+] (m/z): 418.2,420.2.
6th step
The preparation of the chloro-8-of the bromo-1-of 7-(3-chlorine propoxy-)-5-cyclopropyl-5H-pyridazine also [4,5-b] indoles (6a)
Instilled by pyridine 0.75mL (0.01mol) in phosphorus oxychloride 65mL (0.7mol), temperature control less than 30 DEG C stirs 10min.Add compound 5a15.9g (0.04mol), be heated to 80 DEG C of reaction 2.5h.Evaporated under reduced pressure solvent, with frozen water 100mL and ammoniacal liquor 20mL, stirs 30min, has solid to separate out.Suction filtration, washing, dry, with methanol-acetonitrile (1: 1) solution 80mL recrystallization, obtain faint yellow solid 13.3g, yield: 80.1%, m.p.197-199 DEG C, MS [MH
+] (m/z): 414.1,416.2.
7th step
The preparation of the bromo-8-of 7-(3-chlorine propoxy-)-5-cyclopropyl-1-[(the chloro-4-fluorophenyl of 3-) amino]-5H-pyridazine also [4,5-b] indoles (7f)
The ethanol solution hydrochloride 1mL (1.6mmol) of chloro-to compound 6a0.025mol, 3-4-fluoroaniline (0.03mol) and 1.6mol/L is added in Virahol 100mL, backflow 8h.Cooling, suction filtration, washing, dry, obtain yellow solid 7f, yield: 82.4%, MS [MH
+] (m/z): 523.2,525.2.
The synthesis of the 8th step target compound
wherein n=3,
R
1＝3-Cl，4-F；
In 100mLDMF, add 7f (0.05mol), salt of wormwood (13.8g, 0.1mol), fat (ring) amine (0.06mol), stir, be heated to 60 DEG C of reaction 7h.Be cooled to room temperature, add in frozen water, the sedimentation and filtration of precipitation, washing, dry.The product obtained is dissolved in 150mL acetone, and drip the solution that oxalic acid (0.06mol) is dissolved in acetone (30mL), the solid filtering of formation, washing with acetone, vacuum-drying, obtains faint yellow solid.Yield: 81%; M.p.153-155 DEG C of MS [MH
+] (m/z): 532.2 (Br=79), 534.2 (Br=81);
1h-NMR (DMSO-d
6) δ: 9.32 (s, 1H, C
4-H), 8.05 (s, 1H, C
6-H), 8.03 (s, 1H, C
9-H), 7.97 (dd, 1H, J=6.6,2.5Hz, Ar-H), 7.64 (brs, 1H, Ar-H), 7.40 (t, 1H, J=9.0HzAr-H), 4.25 (t, 2H, J=5.7Hz, CH
2cH
2cH
2o), 3.50 (m, 1H, NCH), 3.31 (t, 2H, NCH
2cH
2cH
2), 2.85 (s, 6H, N (CH
3)
2), 2.23 (brs, 2H, CH
2cH
2cH
2), 1.35 (m, 2H, CH
2cH
2), 1.09 (m, 2H, CH
2cH
2).
Experimental example bacteriostatic test
Use the target compound of preparation in embodiment 1, adopt filter paper enzyme classical in this area to carry out bacteriostatic test, wherein:
1. material
1.1 for examination bacterial classification
Escherichia coli ATCC25922, Klebsiella Pneumoniae ATCC700603, enterococcus faecalis ATCC29212, peptostreptococcus ATCC10149, staphylococcus epidermidis ATCC12228 are all purchased from Fu Xiang bio tech ltd, Shanghai.
1.2 nutrient solution
Nutrient agar medium and nutrient broth, all purchased from Chen Yu experimental installation company limited of BeiJing ZhongKe.
1.3 test method
Escherichia coli ATCC25922, Klebsiella Pneumoniae ATCC700603, enterococcus faecalis ATCC29212, peptostreptococcus ATCC10149, staphylococcus epidermidis ATCC12228 are inoculated in agar plate nutritive medium plane, evenly gather during inoculation.
Take the target compound 0.5 gram of preparation in embodiment 1, add 5000 ml sterile waters, ultrasonic 30 minutes, then the filtering with microporous membrane of 0.22 μm, obtained solution.The aseptic circular filter paper sheet of tweezer, sprays above-mentioned solution to complete wetting, is attached in the agar plate nutritive medium plane of inoculated bacteria.Agar plate is placed in the incubator of 37 DEG C, incubation 4 hours.Measure the diameter of bacterial restrain.Measure and average for 3 times.
1.4 result
The mean diameter of the bacterial restrain of escherichia coli ATCC25922 is 11.31mm,
The mean diameter of the bacterial restrain of Klebsiella Pneumoniae ATCC700603 is 9.73mm,
The mean diameter of the bacterial restrain of enterococcus faecalis ATCC29212 is 10.83mm,
The mean diameter of the bacterial restrain of peptostreptococcus ATCC10149 is 9.79mm,
The mean diameter of the bacterial restrain of staphylococcus epidermidis ATCC12228 is 10.58mm,
Show that target compound of the present invention has obvious fungistatic effect.
Claims (1)
1. compound suppresses the application in the medicine of vagina escherichia coli in preparation, and it is characterized in that, described compound has having structure:
Wherein, n=3;
R
1＝3-Cl,4-F；
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410333552.4A CN104072501B (en) | 2014-07-14 | 2014-07-14 | One treats colpitic compound and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410333552.4A CN104072501B (en) | 2014-07-14 | 2014-07-14 | One treats colpitic compound and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104072501A CN104072501A (en) | 2014-10-01 |
| CN104072501B true CN104072501B (en) | 2016-03-02 |
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ID=51594145
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|---|---|---|---|
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|---|---|---|---|---|
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| WO2013174743A1 (en) * | 2012-05-21 | 2013-11-28 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyrimidines |
-
2014
- 2014-07-14 CN CN201410333552.4A patent/CN104072501B/en not_active Expired - Fee Related
Patent Citations (3)
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|---|---|---|---|---|
| CN1995041A (en) * | 2006-12-18 | 2007-07-11 | 沈阳药科大学 | Pyridazineindole derivative and its use |
| US20110021511A1 (en) * | 2006-12-22 | 2011-01-27 | The Medicines Company (Leipzig) Gmbh | Substituted 5h-pyrimido[5,4-b]indoles, method for the production thereof and use thereof for treating non-solid malignant tumors of the blood-producing system |
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| 1-苯氨基-5H-哒嗪并[4,5-b]吲哚类化合物的设计、合成及体外抗肿瘤活性;李荣东等;《中南药学》;20080430;第6卷(第2期);第144-147页 * |
| 1-苯胺基-5H-哒嗪并[4,5-b]吲哚类化合物的合成及体外抗肿瘤活性;李荣东等;《中国药物化学杂志》;20071231;第17卷(第6期);第339-343页 * |
| 5H-哒嗪并[4,5-b]吲哚类新化合物的合成及抗肿瘤细胞增殖活性;翟鑫，等;《中国药物化学杂志》;20101031;第20卷(第5期);第348-352页 * |
| Design, synthesis and antiproliferative activities of novel 5H-pyridazino[4,5-b]indoles;Rong Dong Li等;《Chinese Chemical Letters》;20071231;第1191-1194页 * |
| Synthesis and Anti-Tumor Activities of a Novel Series of Tricyclic 1-Anilino-5H-pyridazino[4,5-b]indoles;Rong Dong Li等;《Arch. Pharm. Chem. Life Sci.》;20071231;第340卷(第8期);第424-428页，Table 1，Figure 1，Scheme 1 * |
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