CN103102283B - Preparation method of chalcone oxime compound and application of the same as novel immunosuppressant - Google Patents
Preparation method of chalcone oxime compound and application of the same as novel immunosuppressant Download PDFInfo
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- CN103102283B CN103102283B CN201110351329.9A CN201110351329A CN103102283B CN 103102283 B CN103102283 B CN 103102283B CN 201110351329 A CN201110351329 A CN 201110351329A CN 103102283 B CN103102283 B CN 103102283B
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- -1 chalcone oxime compound Chemical class 0.000 title claims abstract description 35
- 239000003018 immunosuppressive agent Substances 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 23
- 229960003444 immunosuppressant agent Drugs 0.000 title abstract description 4
- 230000001861 immunosuppressant effect Effects 0.000 title abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 30
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 8
- 238000001953 recrystallisation Methods 0.000 claims description 7
- 150000003935 benzaldehydes Chemical class 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 5
- 229940124589 immunosuppressive drug Drugs 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000008062 acetophenones Chemical class 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 230000006837 decompression Effects 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 150000002923 oximes Chemical class 0.000 claims 1
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 11
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- GVSPXQVUXHMUMA-MDWZMJQESA-N (e)-3-(3,5-ditert-butyl-4-hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Chemical compound C1=CC(OC)=CC=C1C(=O)\C=C\C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 GVSPXQVUXHMUMA-MDWZMJQESA-N 0.000 abstract 1
- IXQYPXRYRSEMAA-UHFFFAOYSA-N n-(1,3-diphenylprop-2-enylidene)hydroxylamine Chemical compound C=1C=CC=CC=1C(=NO)C=CC1=CC=CC=C1 IXQYPXRYRSEMAA-UHFFFAOYSA-N 0.000 abstract 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 11
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- 238000005481 NMR spectroscopy Methods 0.000 description 8
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- 241001465754 Metazoa Species 0.000 description 5
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
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- 230000001506 immunosuppresive effect Effects 0.000 description 4
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- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
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- 0 *C=CC(*)=NO Chemical compound *C=CC(*)=NO 0.000 description 2
- SUYSQRHNTDVWKJ-UHFFFAOYSA-N 1,3-dichlorobenzene;formaldehyde Chemical compound O=C.ClC1=CC=CC(Cl)=C1 SUYSQRHNTDVWKJ-UHFFFAOYSA-N 0.000 description 2
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 2
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- 238000011725 BALB/c mouse Methods 0.000 description 2
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- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 2
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- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
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- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
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- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a chalcone oxime compound, which has a general formula shown in the description, wherein R1 can be a group shown in the description, and R2 can be a group shown in the description. The chalcone oxime derive provided in the invention has an obvious inhibitory effect on activated T cells, and has no significant inhibitory effect on unactivated T cells, so that the chalcone derivative involved in the invention can be applied in preparation of an immunosuppressant. The invention also discloses a preparation method of the chalcone oxime compound.
Description
Technical field
The present invention relates to phenyl styryl ketone oxime compounds and preparation method thereof and purposes as immunosuppressive drug.
Background technology
Immunosuppressor is a kind of important clinical medicine for medical procedure, its for the treatment that comprises graft-rejection and autoimmune disorder as systemic lupus erythematous, rheumatoid arthritis and psoriasis.T lymphocyte has been brought into play indispensable effect in graft-rejection, makes ciclosporin A (CsA), and tacrolimus (FK506's) and sirolimus (rapamycin) are shown one's talent as immunosuppressant treatment.Although immunosuppressive drug has been successfully used to the clinical treatment of organ transplantation and autoimmune disorder, its side effect comprises that liver toxicity, renal toxicity, malignant tumour, infection, Cardiovascular Toxicity etc. can not be ignored.Therefore, find new adjusting immune response, and efficient, need to never the stopping of the immunosuppressive drug of the potential clinical application of the conduct of low toxicity.
According to research reports, the compound of chalcone has the multiple biological activitys such as anti-inflammatory, antiviral, anti-malarial, immunosuppression, and the T cell proliferation in immune response is had to obvious restraining effect.Some oxime compounds also has certain immunosuppressive activity.Therefore,, as the oxime derivatives of phenyl styryl ketone, its research aspect immunosuppression has larger potentiality equally.
Summary of the invention
The object of the present invention is to provide the novel phenyl styryl ketone oxime compounds of a class and their preparation method and purposes.
Technical scheme of the present invention is as follows:
1. a class phenyl styryl ketone oxime derivatives, is characterized in that it has following general formula:
In formula: R
1-be:
R
2-be:
A method of preparing above-mentioned oxime compounds, it is made up of the following step:
Step 1. is in methanol solution, add the compound of corresponding acetophenones and the compound of corresponding benzaldehydes, the ratio of the amount of substance of the compound of acetophenones and the compound of benzaldehydes is 1: 1 left and right, add the potassium hydroxide aqueous solution of 6 moles every liter, potassium hydroxide is 2.5: 1 with the amount of substance ratio of methyl phenyl ketone again, and stirring at room temperature is until there is solid to form, by solid filtering, wash with frozen water and ice methyl alcohol again, the solid obtaining is dissolved in to anhydrous methanol recrystallization and purifies
Solid after the purification that step 2. obtains step 1 is dissolved in pyridine, adds the oxammonium hydrochloride of 6 times of amount of substances, is heated with stirring to 60 ℃, reaction is cooling after spending the night 12 hours, and filtrate decompression evaporate to dryness, washes the solid obtaining with water, use again dehydrated alcohol recrystallization, obtain the compound of phenyl styryl ketone oximes.
Above-mentioned method for making, in described step 1, the consumption of methyl alcohol is that the compound of every mmole benzaldehydes adds 5ml.
Above-mentioned method for making, in described step 2, the consumption of pyridine is that every mmole oxammonium hydrochloride adds 1ml.
The T cell obvious restraining effect of phenyl styryl ketone oxime compounds of the present invention to activation, and to the restraining effect of non-activated T cell a little less than, therefore oxime compounds of the present invention can be applied preparing in immunosuppressive drug.
Embodiment
Embodiment mono-: the preparation of (2E)-1-(4-chloro-phenyl-)-3-(4-fluorophenyl) phenyl styryl ketone oxime (compound 1)
In 100ml single necked round bottom flask, add parachloroacetophenone (10mmol) and p-Fluorobenzenecarboxaldehyde (10mmol), add the dissolve with methanol of 50ml, the potassium hydroxide aqueous solution (25mmol, 4.17mL) of 6 moles every liter adding again.Stirring at room temperature reaction, to there being solid to produce, then by solid filtering, then is washed one time with ice methyl alcohol and frozen water, obtains yellow solid.The solid obtaining is put into the beaker of 100ml, added dehydrated alcohol to dissolving completely, then after recrystallization, filter, obtain yellow lenticular material 1-(4-chloro-phenyl-)-3-(4-fluorophenyl) phenyl styryl ketone.Moved into again in the single necked round bottom flask of 100ml, added the oxammonium hydrochloride of 6 times of molar masss, be dissolved in pyridine (10ml).Be heated with stirring to 60 ℃, backflow is spent the night and within 12 hours, is used thin layer chromatography detection reaction later, until react completely, cooled and filtered, filtrate decompression evaporate to dryness, obtains yellow particulate state compound after recrystallization, then uses dehydrated alcohol recrystallization, obtain yellow crystals shape material, i.e. target phenyl styryl ketone oxime compounds.Productive rate: 35%.Mp?150-152℃。
1H?NMR(300Hz，CDCl
3)：5.95-6.00(m，1H)；6.85(d，J＝8.76Hz，2H)；6.94(d，J＝8.79Hz，2H)；7.16(d，J＝8.61Hz，2H)；7,26(s，1H)；7.68(d，J＝8.79，2H).ESI-MS：277.05(C
15H
12ClFNO，[M+H]
+).Anal.Calcd?for?C
15H
12ClFNO：C，65.35；H，4.02；N，5.08.FOUND：C，65.21；H，4.20；N，5.21.
Embodiment bis-: the preparation of (2E)-1-(4-chloro-phenyl-)-3-(thiophene-2-yl) phenyl styryl ketone oxime (compound 2)
Preparation method is with embodiment mono-.Replace p-Fluorobenzenecarboxaldehyde with thiophene-2-formaldehyde, obtain yellow crystals shape target compound.Productive rate 30%.Mp?140-142℃.
1H?NMR(300Hz，CDCl
3)：6.83-6.70(m，1H)；6.97-7.03(m，1H)；7.09(d，J＝3.66Hz，1H)；7.29-7.34(t，J＝26.7Hz，1H)；7.39-7.48(m，5H).ESI-MS：264.02(C
13H
11ClNOS，[M+H]
+).Anal.Calcd?for?C
13H
10ClNOS：C，59.20；H，3.82；N，5.31.FOUND：C，60.12；H，3.76；N，5.44.
Embodiment tri-: the preparation of (2E)-1-(4-bromophenyl)-3-(thiophene-2-yl) phenyl styryl ketone oxime (compound 3)
Preparation method is with embodiment mono-.Replace parachloroacetophenone with parabromoacetophenone, replace p-Fluorobenzenecarboxaldehyde with thiophene-2-formaldehyde, obtain yellow crystals shape target compound.Productive rate 25%.Mp?129-132℃.
1H?NMR(300Hz，CDCl
3)：7.08-7.11(m，1H)；7.28(d，J＝10.26Hz，1H)；7.37-7.44(m，2H)；7.64(d，J＝8.43Hz，2H)；7.87(d，J＝8.58Hz，2H)；7.95(d，J＝15.36Hz，1H).ESI-MS：307.97(C
13H
11BrNOS，[M+H]
+).Anal.Calcd?for?C
13H
10BrNOS：C，50.66；H，3.27；N，4.54.FOUND：C，51.89；H，3.38；N，4.32.
Embodiment tetra-: the preparation of (2E)-1-(4-bromophenyl)-3-(4-chloro-phenyl-) phenyl styryl ketone oxime (compound 4)
Preparation method is with embodiment mono-.Replace parachloroacetophenone with parabromoacetophenone, replace p-Fluorobenzenecarboxaldehyde with 4-chloro-benzaldehyde, obtain yellow crystals shape target compound.Productive rate 38%.Mp?166-170℃.
1H?NMR(300Hz，CDCl
3)：7.39-7.47(m，3H)；7.58(d，J＝6.57Hz，2H)；7.64-7.67(m，2H)；7.76(d，J＝15.75Hz，1H)；7.86-7.90(m，2H).ESI-MS：337.61(C
15H
12BrClNO，[M+H]
+).Anal.Calcd?for?C
15H
11BrClNO：C，53.52；H，3.29；N，4.16.FOUND：C，51.67；H，3.16；N，4.29.
Embodiment five: the preparation of (2E)-1-(4-bromophenyl)-3-(2,4 dichloro benzene base) phenyl styryl ketone oxime (compound 5)
Preparation method is with embodiment mono-.Replace parachloroacetophenone with parabromoacetophenone, replace p-Fluorobenzenecarboxaldehyde with 2,4 dichloro benzene formaldehyde, obtain yellow crystals shape target compound.Productive rate 34%.Mp?174-177℃.
1H?NMR(300Hz，CDCl
3)：7.16-7.20(m，1H)；7.60(d，J＝8.58Hz，4H)；7.80-7.83(m，4H).ESI-MS：372.06(C
15H
11BrCl
2NO，[M+H]
+).Anal.Calcd?for?C
15H
10BrCl
2NO：C，48.55；H，2.72；N，3.77.FOUND：C，48.64；H，2.83；N，3.62.
Embodiment six: the preparation of (2E)-1-(4-bromophenyl)-3-(4-fluorophenyl) phenyl styryl ketone oxime (compound 6)
Preparation method is with embodiment mono-.Replace parachloroacetophenone with parabromoacetophenone, replace p-Fluorobenzenecarboxaldehyde with p-Fluorobenzenecarboxaldehyde, obtain yellow crystals shape target compound.Productive rate 32%.Mp?180-184℃.
1H?NMR(300Hz，CDCl
3)：7.09-7.14(m，2H)；7.40(d，J＝15.54Hz，1H)；7.57-7.67(m，4H)；7.75-7.80(t，J＝7.86HZ，1H)；7.86-7.89(m，2H).ESI-MS：307.97(C
15H
12BrFNO，[M+H]
+).Anal.Calcd?for?C
15H
11BrFNO：C，56.27；H，3.46；N，4.37.FOUND：C，56.39；H，3.54；N，4.29.
Embodiment seven: the preparation of (2E)-1-(4-tolyl)-3-(4-fluorophenyl) phenyl styryl ketone oxime (compound 7)
Preparation method is with embodiment mono-.Replace parachloroacetophenone with p-methyl aceto phenone, replace p-Fluorobenzenecarboxaldehyde with p-Fluorobenzenecarboxaldehyde, obtain yellow crystals shape target compound.Productive rate 44%.Mp111-115℃.
1H?NMR(300Hz，CDCl
3)：2.42(s，3H)；6.94(d，J＝8.79Hz，2H)；7.35(d，J＝15.54Hz，1H)；7.59-7.65(m，4H)；7.79(d，J＝15.54Hz，1H)；7.88(d，J＝8.61Hz，2H).ESI-MS：256.29(C
16H
15FNO，[M+H]
+).Anal.Calcd?for?C
16H
14FNO：C，75.28；H，5.53；N，5.49.FOUND：C，75.11；H，5.42；N，5.57.
Embodiment eight: the preparation of (2E)-1-(4-tolyl)-3-(4-chloro-phenyl-) phenyl styryl ketone oxime (compound 8)
Preparation method is with embodiment mono-.Replace parachloroacetophenone with p-methyl aceto phenone, replace p-Fluorobenzenecarboxaldehyde with 4-chloro-benzaldehyde, obtain yellow crystals shape target compound.Productive rate 42%.Mp?144-146℃.
1HNMR(300Hz，CDCl
3)：2.41(s，3H)；6.75(d，J＝16.65Hz，1H)；7.24(d，J＝9.87Hz，2H)；7.29-7.44(m，6H)；7.63(d，J＝16.44Hz).ESI-MS：272.74(C
16H
15ClNO，[M+H]
+).Anal.Calcd?for?C
16H
14ClNO：C，70.72；H，5.19；N，5.15.FOUND：C，70.58；H，5.25；N，5.20.
Embodiment nine: the preparation of (2E)-1-(4-tolyl)-3-(2,4 dichloro benzene base) phenyl styryl ketone oxime (compound 9)
Preparation method is with embodiment mono-.Replace parachloroacetophenone with p-methyl aceto phenone, replace p-Fluorobenzenecarboxaldehyde with 2,4 dichloro benzene formaldehyde, obtain yellow crystals shape target compound.Productive rate 39%.Mp?152-156℃.
1H?NMR(300Hz，CDCl
3)：2.42(s，3H)；7.16-7.27(m，4H)；7.38-7.45(m，3H)；7.59(d，J＝16.65Hz，1H)；7.71(d，J＝9.51，1H).ESI-MS：307.19(C
16H
14Cl2NO，[M+H]
+).Anal.Calcd?for?C
16H
13Cl
2NO：C，62.76；H，4.28；N，4.57.FOUND：C，62.65；H，4.17；N，4.69.
Embodiment ten: the research of phenyl styryl ketone oxime compounds immunosuppressive activity
Adopt MTT[3-(4,5)-bis-methyl-2-thiazoles-(2,5)-phenyl bromination tetrazole indigo plant] method measure oxime compounds to activation T cell and non-activated T cell minimum inhibitory concentration (minimal inhibitory concentration, MIC).Adopt the method for flow cytometer and immunoblotting to carry out mechanism of action detection to the best compound of immunocompetence.
(1) animal is prepared: purchased from the female BALB/c mouse in 6 to 8 week age of Jiangsu Province's Experimental Animal Center.At 21 ± 2 ℃, mouse keep freely eating food and water, and kept for 12 little time/secretly cycles.Laboratory Animal Welfare and experimental arrangement are to carry out in strict accordance with laboratory animal guide (science and China, technical division in 2006) the ethics rules guide relevant with Nanjing University.Reduce to full capacity the misery of animal and reduce the quantity that uses animal.
(2) cell is prepared with reagent: separate lymph-node cell from BALB/c mouse at 37 ℃, in the air of 5.0% carbonic acid gas humidification, in 1640 substratum that are aided with 10% foetal calf serum, cultivate.Anti-CD3, anti-CD28 murine antibody, purchased from BD Pharmingen.Annexin V-FITC/PI test kit is purchased from the U.S. biotechnology of crystalline substance.Anti-caspase-3 antibody and the anti-PARP antibody of splitting is purchased from Santa Cruz biotech company.Anti-ribose antibody is purchased from Cell Signaling Technology, Inc..Every other chemical obtains Chemical Co., Ltd. of Sigma.
(3) cell proliferation experiment: lymph-node cell is with 5 × 10
5the density of individual/plate is cultivated in 96 holes, with the compound of different concns with the anti-CD28 Co stituation of anti-CD3/, continue 72h.4h before cultivation finishes, every hole adds 20 μ l MTT, and the multiplicative stage starts.After end, remove after supernatant liquor, add 20 μ l DMSO Rong Xie formazan crystallizations.By the absorbancy under enzyme linked immunosorbent assay instrument test 540nm.
(4) cell toxicity test: by cell with 5 × 10
5the density in individual/hole adds in 96 orifice plates, then adds the compound of gradient concentration to cultivate 72h.Before end is cultivated, the every hole of 4h adds the MTT of 20 μ l.And then add the DMSO Rong Xie formazan crystal of 200 μ l.Finally survey the absorbance of 540nm.
(5) statistical study
All experiments have all repeated 3-5 time, all obtain similar result.These two experimental group P values are tested with two tail student t-checks.It is 0.05 that significance level fixes on P value.If be suitable for, data report is mean+SD (SD).
The calculating of inhibiting rate: the inhibiting rate of Growth of Cells calculates according to the following formula:
Growth inhibition ratio=(1-survival rate) × 100%=[1-(OD
experiment-OD
blank)/(OD
contrast-OD
empty in vain)] × 100% (OD
experimentrepresent the average optical of testing drug group, OD
contrastrepresent the average optical of control group, OD
blankrepresent the average optical of control group).
Half-inhibition concentration (IC
50) be defined as the drug level in the time of the survival of 50% tumour cell.According to the optical density(OD) (OD value) of measuring, make the typical curve of inhibitory rate of cell growth, on typical curve, try to achieve its corresponding drug level.
The inhibition IC of the T cell to activation of phenyl styryl ketone oxime compounds of the present invention
50value is in table 1, to the inhibition CC of non-activated T cell
50value is in table 2.
The inhibition IC of the T cell to activation of the listed oxime compounds of table 1 the present invention
50value (μ M) and the inhibition CC to non-activated T cell
50value
CsA: positive control.
Claims (5)
1. a class phenyl styryl ketone oxime derivatives, is characterized in that it has following general formula:
In formula: R
1-be:
R
2-be:
2. prepare a method for above-mentioned phenyl styryl ketone oxime compounds, it is characterized in that it is made up of the following step:
Step 1. is in methanol solution, add the compound of corresponding acetophenones and the compound of corresponding benzaldehydes, the ratio of the amount of substance of the compound of acetophenones and the compound of benzaldehydes is 1: 1, add the potassium hydroxide aqueous solution of 6 moles every liter, potassium hydroxide is 2.5: 1 with the amount of substance ratio of methyl phenyl ketone again, and stirring at room temperature is until there is solid to form, by solid filtering, wash with frozen water and ice methyl alcohol again, the solid obtaining is dissolved in to anhydrous methanol recrystallization and purifies
Solid after the purification that step 2. obtains step 1 is dissolved in pyridine, adds the oxammonium hydrochloride of 6 times of amount of substances, is heated with stirring to 60 ℃, reaction is cooling after spending the night 12 hours, and filtrate decompression evaporate to dryness, washes the solid obtaining with water, use again dehydrated alcohol recrystallization, obtain the compound of phenyl styryl ketone oximes.
3. method for making according to claim 2, is characterized in that: in described step 1, the consumption of methyl alcohol is that the compound of every mmole benzaldehydes adds 5ml.
4. method for making according to claim 2, is characterized in that: in described step 2, the consumption of pyridine is that every mmole oxammonium hydrochloride adds 1ml.
According to the phenyl styryl ketone 9 oxime derivate described in claim in the application of preparing in immunosuppressive drug.
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| PL234611B1 (en) * | 2018-02-02 | 2020-03-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4-phenyl-2-methylchalcone and (Z)-oxime of 4'-phenyl-2-methylchalcone and method for obtaining them simultaneously |
| PL234612B1 (en) * | 2018-02-02 | 2020-03-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4'-phenyl-2-methoxychalcone and (Z)-oxime of 4'-phenyl-2-methoxychalcone and method for obtaining them simultaneously |
| PL234093B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4'-phenyl-4-fluorochalcone and (Z)-oxime of 4'-phenyl-4-fluorochalcone and method for obtaining them simultaneously |
| PL234613B1 (en) * | 2018-02-02 | 2020-03-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4'-phenylchalcone and (Z)-oxime of 4'-phenylchalcone and method for obtaining them simultaneously |
| PL234089B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 2,4-dimethoxy-4'-phenylchalcone and (Z)-oxime of 2,4-dimethoxy-4'-phenylchalcone and method for obtaining them simultaneously |
| PL234097B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4-bromo-4'-phenylchalcone and (Z)-oxime of 4-bromo-4'-phenylchalcone and method for obtaining them simultaneously |
| PL234090B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4-ethoxy-4'-phenylchalcone and (Z)-oxime of 4-ethoxy-4'-phenylchalcone and method for obtaining them simultaneously |
| PL234091B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4'-phenyl-4-nitrochalcone and (Z)-oxime of 4'-phenyl-4-nitrochalcone and method for obtaining them simultaneously |
| PL234096B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4-chloro-4'-phenylchalcone and (Z)-oxime of 4-chloro-4'-phenylchalcone and method for obtaining them simultaneously |
| PL234092B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4'-phenyl-4-methylchalcone and (Z)-oxime of 4'-phenyl-4-methylchalcone and method for obtaining them simultaneously |
| PL234095B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4'-phenyl-4-carboxychalcone and (Z)-oxime of 4'-phenyl-4-carboxychalcone and method for obtaining them simultaneously |
| PL234094B1 (en) * | 2018-02-02 | 2020-01-31 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4-ethyl-4'-phenylchalcone and (Z)-oxime of 4-ethyl-4'-phenylchalcone and method for obtaining them simultaneously |
| PL235027B1 (en) * | 2018-02-27 | 2020-05-18 | Wrocław University Of Environmental And Life Sciences | (E)-oxime of 4'-phenyl-4-methoxychalcone and (Z)-oxime of 4'-phenyl-4-methoxychalcone and method for obtaining them simultaneously |
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