CN103142569A - 2, 6-diisopropyl benzoic acid and application of 2, 6-diisopropyl benzoic acid derivative serving as neuroprotective agent - Google Patents
2, 6-diisopropyl benzoic acid and application of 2, 6-diisopropyl benzoic acid derivative serving as neuroprotective agent Download PDFInfo
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- CN103142569A CN103142569A CN2013100613491A CN201310061349A CN103142569A CN 103142569 A CN103142569 A CN 103142569A CN 2013100613491 A CN2013100613491 A CN 2013100613491A CN 201310061349 A CN201310061349 A CN 201310061349A CN 103142569 A CN103142569 A CN 103142569A
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- benzoic acid
- diisopropyl
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- diisopropyl benzoic
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- AGBGSHYCQQNNEH-UHFFFAOYSA-N 2,6-di(propan-2-yl)benzoic acid Chemical compound CC(C)C1=CC=CC(C(C)C)=C1C(O)=O AGBGSHYCQQNNEH-UHFFFAOYSA-N 0.000 title abstract description 13
- 239000004090 neuroprotective agent Substances 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 12
- 230000000324 neuroprotective effect Effects 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- 210000005036 nerve Anatomy 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- -1 methylol, carboxymethyl Chemical group 0.000 claims description 3
- 230000001681 protective effect Effects 0.000 abstract description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 abstract description 5
- 235000013922 glutamic acid Nutrition 0.000 abstract description 5
- 239000004220 glutamic acid Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 abstract 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 abstract 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 abstract 1
- 230000004693 neuron damage Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 206010008118 cerebral infarction Diseases 0.000 description 7
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
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- 239000005711 Benzoic acid Substances 0.000 description 5
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- 235000010233 benzoic acid Nutrition 0.000 description 5
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- 229930195712 glutamate Natural products 0.000 description 5
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- MDFWXZBEVCOVIO-UHFFFAOYSA-N 4,7,7-trimethylbicyclo[2.2.1]heptan-3-amine Chemical compound C1CC2(C)C(N)CC1C2(C)C MDFWXZBEVCOVIO-UHFFFAOYSA-N 0.000 description 4
- 201000006474 Brain Ischemia Diseases 0.000 description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 description 4
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- 230000000694 effects Effects 0.000 description 4
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- 239000004310 lactic acid Substances 0.000 description 4
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
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- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
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- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
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- 230000001954 sterilising effect Effects 0.000 description 2
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- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
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- HORQAOAYAYGIBM-UHFFFAOYSA-N 2,4-dinitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O HORQAOAYAYGIBM-UHFFFAOYSA-N 0.000 description 1
- WKBALTUBRZPIPZ-UHFFFAOYSA-N 2,6-di(propan-2-yl)aniline Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N WKBALTUBRZPIPZ-UHFFFAOYSA-N 0.000 description 1
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
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- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N benzyl-alpha-carboxylic acid Natural products OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
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- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 1
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- 230000003961 neuronal insult Effects 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
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- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses 2, 6-diisopropyl benzoic acid and the application of 2, 6-diisopropyl benzoic acid derivative serving as a neuroprotective agent, specifically the application of the compound in the preparation of neuroprotective medicines. In the compound, R is carboxyl, hydroxymethyl, carboxymethyl or hydroxyethyl. The compound disclosed by the invention has a good protective effect on glutamic acid induced neuron damage.
Description
Technical field
The invention belongs to pharmaceutical field, a class 2 is provided, the application in the preparation nerve protection medicine of 6-diisopropyl benzoic acid and derivant thereof.
Background technology
Neuroprotective is a focus of cerebral infarction medicine development.At present, for numerous protection reagent of the different links exploitations of cerebral infarction cascade reaction, except the free radical scavenger Edaravone, be all that animal is effective, clinical invalid or poor effect, or can not be applied to clinical because of serious side effects.Therefore, the exploitation of novel nerve protective agent and screening are the emphasis of studying at present.
Studies show that, glutamic acid plays an important role in the cell injury that cerebral ischemia causes, when cerebral ischemia occurs, a large amount of releases of glutamic acid can cause the death of neuronal cell.The damage of neurocyte causes lactic acid dehydrogenase (LDH) to be discharged into the extracellular, suppresses the rate that spills of LDH by measuring medicine and can estimate medicine to the protective effect of neuronal cell.
The neuronal cell lactic acid dehydrogenase (LDH) that stimulates based on glutamic acid discharges model to the selection result of compound, and the present invention finds a class 2, and 6-diisopropyl benzoic acid and derivant thereof have protective effect to neuronal cell.
Summary of the invention
The technical problem that solves: provide a class 2, the application in the preparation nerve protection medicine of 6-diisopropyl benzoic acid and derivant thereof.
Technical scheme:
Compound
For the preparation of the application in nerve protection medicine, wherein R is carboxyl, methylol, carboxymethyl or ethoxy.
The application of above-claimed cpd in neuroprotective.
Compound as shown in general formula (I) is the salt of acceptable alkali pharmaceutically, and the salt of alkali is potassium salt, sodium salt.
Compound as shown in general formula (I) and the pharmaceutically application of salt in the preparation nerve protection medicine of acceptable alkali thereof.
Compound in the present invention is known compound, its synthetic can according to or the method for reference literature synthesize.
The synthetic of the compound that the present invention relates to can be represented by following synthetic signal route.
Synthetic signal route:
Beneficial effect:
Compound in the present invention has stronger protective effect to the neuronal damage of glutamate induction.
Description of drawings
Fig. 1: the anti-apoplexy effect of 2,6-diisopropyl benzoic acid (1).
The specific embodiment
The following examples can make those skilled in the art can comprehensively understand the present invention, but do not limit the present invention in any way.
Embodiment 12,6-diisopropyl iodobenzene synthetic
Measure 2,6-diisopropyl aniline 3.2mL (15.8mmol) is in 100mL three neck round-bottomed flasks, add 30mL water, add concentrated hydrochloric acid 15mL under the mechanical agitation of limit, after adding, drip with constant pressure funnel the aqueous solution that sodium nitrite 1.18g (17.4mmol) is dissolved in 4mL under ice-water bath, react again 1h under 4 ℃.Take iodine 4.40g (21.28mmol) and potassium iodide 6.04g (36mmol) and be dissolved in the 10mL frozen water getting mixed liquor.Mixed liquor is dropped in reaction system, after 30min, add entry 40mL, dichloromethane 100mL, ambient temperature overnight adds hydration sodium thiosulfate 6.30g (25.4mmol), stirring reaction 20min.Elimination black precipitate, solution separatory funnel separatory, water merges organic facies with chloroform (60mL * 2 time) extraction, with 10%wt hypo solution 50mL washing, saturated common salt water washing, anhydrous magnesium sulfate drying.The elimination desiccant boils off solvent, carries out column chromatography (petroleum ether: ethyl acetate=200:1, volume ratio) with silicagel column and gets flaxen liquid 1.54g, productive rate 34%.
1H?NMR(CDCl
3,300MHZ):1.21-1.24(s,12H),3.37-3.43(m,1H),3.44-3.51(m,1H),7.04-7.06(s,1H),7.11-7.13(s,1H),7.17-7.23(m,1H).
Embodiment 22,6-diisopropyl benzoic acid (1) synthetic
Get 2,6-diisopropyl iodobenzene 1.44g (5mmol) in the 100mL three-necked bottle, add anhydrous tetrahydro furan 3mL, fully replace with nitrogen in the biexhaust pipe system.Take acetone as coolant, reaction system is dropped to-78 ℃ with liquid nitrogen.Drip the n-butyllithium solution 5mL (10mmol) of 2mol/L under stirring with syringe, inject complete after, keep-78 ℃ to react 1h.Temperature is risen to room temperature, pass into CO after half an hour
2Reaction 20h.Add 2N hydrochloric acid solution 5mL, use extracted with diethyl ether after stirring, merge organic facies, solvent evaporated.Residue washs with ether with 2N NaOH solution 5mL dissolving.Water is used extracted with diethyl ether with 2N hydrochloric acid solution 10mL neutralization, combining extraction liquid, and anhydrous sodium sulfate drying filters, and evaporate to dryness gets white crystal 0.54g, productive rate 54%.
1H?NMR(CDCl
3,300MHZ):1.28(s,12H),2.82-2.96(m,2H),7.16-7.20(s,2H),7.26-7.36(m,1H),13.05(s,1H).
Embodiment 32,6-diisopropyl benzyl alcohol (2) synthetic
The solution that 2,6-diisopropyl benzoic acid 2.1g (10mol) is dissolved in 10mL THF splashes into LiAlH
40.57g the solution at 20mLTHF.After adding, backflow 2h.After letting cool, add 10%wtNH
4Cl solution 20mL, with EtOAc extraction, saturated common salt water washing, anhydrous sodium sulfate drying filters, and is concentrated, gets solid 1.83g, productive rate 95%.
1HNMR(CDCl
3,500MHZ):1.28(s,12H),2.92-3.12(m,2H),4.79(s,2H),6.86-7.05(m,3H).
Embodiment 42,6-diisopropyl phenethanol (3) synthetic
Get 2,6-diisopropyl iodobenzene 2.88g (10mmol) in the 100mL three-necked bottle, add anhydrous tetrahydro furan 3mL, fully replace with nitrogen in the biexhaust pipe system.Take acetone as coolant, reaction system is dropped to-78 ℃ with liquid nitrogen.Drip the n-butyllithium solution 10mL (20mmol) of 2mol/L under stirring with syringe, inject complete after, keep-78 ℃ to react 1h.Temperature is risen to-10 ℃, the solution that oxirane 7mL (0.14mol) is dissolved in the 20mL dry tetrahydrofuran splashes in reactant liquor, drips off rear stirred overnight at room temperature.Add saturated ammonium chloride solution 50mL next day, adds dilute hydrochloric acid (1: 1 volume ratio dilute with water) 100mL, with ethyl acetate extraction (60mL * 3 time).Combining extraction liquid, the saturated common salt water washing, anhydrous sodium sulfate drying filters, evaporate to dryness, residue gets white cotton shape solid 0.53g, productive rate 28% with silica gel column chromatography (petroleum ether: ethyl acetate=200:1, volume ratio).
1H?NMR(CDCl
3,500MHZ):1.22(d,12H,J=6.90Hz),2.82-2.96(m,2H),3.66-3.74(m,2H),3.89-3.95(m,2H),7.09-7.21(m,2H),7.26-7.36(m,1H).
Embodiment 52,6-diisopropyl hyacinthin synthetic
2,6-diisopropyl phenethanol 1.36g (6.6mmol) is dissolved in the 50mL dichloromethane, adds pyridinium chlorochromate 3.08g (14mmol).Stirring at room 2 hours is steamed except dichloromethane, and with the dilution of 75mL ethyl acetate, washing, saturated common salt washing, anhydrous sodium sulfate drying filters, and concentrated, column chromatography (petroleum ether: ethyl acetate=50:1, volume ratio) gets white solid 0.85g, productive rate 63%.Product is directly used in next step reaction.
Embodiment 62,6-diisopropyl phenylacetic acid (4) synthetic
With 2,6-diisopropyl hyacinthin 0.82g (4.0mmol) is dissolved in the mixed solvent of the 50mL tert-butyl alcohol, 10mL oxolane, add under ice bath 3.3g sodium dihydrogen phosphate (28mmol) and 2.4g sodium chlorite (80%, in 36mL aqueous solution 21mmol).Stir 20min under ice bath, rose to stirring at room 3 hours, in impouring saturated ammonium chloride solution 150mL, ethyl acetate 200mL extracts, wash twice, saturated common salt washing twice, anhydrous sodium sulfate drying filters, and is concentrated, column chromatography (petroleum ether: ethyl acetate=8:1, volume ratio), get white solid 0.42g, productive rate 48%.
1H?NMR(CDCl
3,500MHz):0.95-1.20(m,12H),2.85-3.15(m,2H),3.74(s,2H),7.10-7.30(m,3H).
In embodiment 7 embodiment, target compound is for the protective effect of glutamate induction primary neuron cell injury
Experimental principle:
Lactic acid dehydrogenase (Lactate dehydrogenase, LDH) algoscopy is adopted in this experiment.LDH is present in cell, and the outer content of normal condition lower eyelid is less, and when the cell damaged, LDH can be discharged into outside born of the same parents, therefore detects the rate that spills of LDH and can judge cell damaged degree.LDH can generate acetone acid by catalysis lactic acid, and acetone acid and 2,4 dinitrophenyl hydrazine reaction generate the acetone acid dinitrophenylhydrazone, are brownish red in alkaline solution, can obtain enzyme activity by colorimetric.
The extraction of mouse cortex primary neuron:
Get pregnant age and be the pregnant mice of ICR of 15-16 days, after the cervical vertebra dislocation, the uterus is separated with Placenta Hominis, successively the tire Mus of taking out is placed in 0.1% bromogeramine solution, 75% alcohol disinfecting.Left hand is the tire Mus fixedly, and the right hand separates cranium with ophthalmic tweezers, exposes cerebral hemisphere, with the careful gripping of ophthalmic tweezers both sides cerebral cortex, is placed in the plate that is placed with 10mL D-hanks.After all taking, peel off meninges and be placed in the plate that another one is placed with 10mL D-hanks, and then draw 5mL D-hanks washing once.With curved tweezer, cortex is shredded, (2mL0.25% pancreatin+2mLD-hanks) be added to plate transfers in small beaker, after mixing, digests 10min in incubator to take out 0.125% the pancreatin be placed in 37 ℃ of incubators.After taking out from incubator, add 5mL DMEM+10%wtFBS to stop digestion, after the piping and druming mixing, be transferred in centrifuge tube 1500rpm, centrifugal 5min.Supernatant discarded, then add 4mL DMEM+10%wtFBS, after the piping and druming mixing, recentrifuge, 1500rpm, 5min.Supernatant is discarded, add 2mL neuron culture medium (98mL Neurobasal Medium, 2mL B27,50 μ mol/l L-glutamine400 μ L, penicillin 50 μ L, streptomycin 50 μ L), piping and druming disperses cell, crosses 400 mesh sieves.After diluting 10 times, carry out cell counting, then inoculate, the 24 every hole inoculation of orifice plate 300 μ L, labelling is placed in incubator well and cultivates.Change culture medium after one day, siphon away 120 μ L, then add 450 μ L.Again change liquid on the 4th day, and siphoned away 200 μ L, then add 300 μ L.The 7th day, the glutamic acid modeling.
Glutamate injury model:
First 24 orifice plate every holes are settled to 300 μ L, every hole administration 0.3 μ L then, each drug level is established 3 parallel holes, after half an hour, every hole is given Glu3 μ L and Gly3 μ L again, during the observation of cell state, after half an hour, full dose is changed liquid, is placed in and collects culture medium (born of the same parents are outer) after incubator 8h.After using again the PBS washed twice, add 300 μ L distilled waters, then collect afterwards (in born of the same parents) 3 times in-80 ℃ of multigelations.-20 ℃ of preservations.
LDH spills the mensuration of rate:
Table 1 spills the operating procedure that rate is measured
Add after NaOH solution mixing again, sample is joined respectively 96 orifice plates, every hole 200 μ L, each hole absorbance when then measuring 440nm on microplate reader.
Spill the outer measured value of rate=born of the same parents/(measured value in the outer measured value+born of the same parents of born of the same parents) * 100%
The evaluation of result foundation:
According to the suppression ratio of following formula computerized compound to the neuronal cell injury of glutamate induction:
Suppression ratio=(the glutamic acid group spills rate-compound group and spills rate)/(the glutamic acid group spills rate-matched group and spills rate) * 100%
The suppression ratio of compound is the meansigma methods of three parallel hole measured values.
Result:
Table 2LDH spills suppression ratio
Above-mentioned test shows: the primary neuron cell injury of 1 ~ 4 pair of glutamate induction of compound has protective effect, and wherein 2,6-diisopropyl benzoic acid (1) is 10 of test
-7~ 10
-5Stronger neuroprotective is arranged, 10 in the M concentration range
-5During M, its LDH discharges suppression ratio up to 36.8%.Our research also finds, menthyl formic acid (5) and bornyl amine (6) have neurotoxicity in the concentration range of test.
Embodiment 82, the neuroprotective of 6-diisopropyl benzoic acid (1) on animal model
The preparation of cerebral ischemic model:
Adopt standby middle cerebral artery occlusion (Middle cerebral artery, MCAO) the cerebral ischemia re-pouring model of internal carotid artery line bolt legal system.After animal is anaesthetized with 10% chloral hydrate (4.0mL/kg), dorsal position is fixed on operating-table, sterilization skin, cervical region medisection, separate right carotid, external carotid artery, internal carotid artery, peel off gently vagus nerve, ligation is also cut off external carotid artery, follow internal carotid artery forward, the tie wings arteria palatina.Folder closes the common carotid artery proximal part, make a kerf from the far-end of the ligature of external carotid artery, inserting external diameter is the nylon wire of 0.285mm, and the top is through polishing and lubricated, enter internal carotid artery through the common carotid artery bifurcated, then till slowly being inserted into slight resistance (from the about 20mm of crotch), all blood confessions of blocking-up middle cerebral artery, cerebral ischemia is after 2.0 hours, extract gently nylon wire, recover blood for also at once passing through the tail vein injection medicine, sew up skin of neck, sterilization.Use the rat hot plate to keep 37.0 ± 0.5 ℃ of Rat-rectum temperature in whole operation process.
The evaluation of neuroprotective:
the chloral hydrate anesthesia of animal 10%wt after recovery blood was for 24 hours, broken end is got brain, remove olfactory bulb, cerebellum and low brain stem, with normal saline flushing brain surface bloodstain, suck remained on surface water mark, place 7min in-80 ℃, make vertically downward coronal section in the sight line crossing plane immediately after taking-up, and cut a slice every 2mm backward, the brain sheet is placed in uses PBS(0.2mol/L, pH7.4~7.8) freshly prepared TTC(20g/L) in dye liquor in 37 ℃ of incubation 90min, normal cerebral tissue dyes peony, ischemic tissue of brain is pale asphyxia, after normal saline flushing, rapidly the brain sheet is arranged from front to back in order, blot remained on surface water mark, take pictures.The infarct size of comparison model group and administration group, the neuroprotective of evaluation medicine.
Experimental result is seen accompanying drawing 1, and after result showed 2,6-diisopropyl benzoic acid (1) 1mg/Kg intravenously administrable, obviously reduced than the infarct size of model group in the cerebral infarction dead band of mice.
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