CN104784176A - Application of derivative of Daphmalenine A in preparation of acute renal failure resisting drugs - Google Patents
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- BNSQPPYRCUIFLZ-LSLDVNGTSA-N methyl (1R,5S,8S,11S,12R,15R,17R)-8-hydroxy-3-methyl-9-oxo-15-(3-oxopentyl)-13-oxa-3-azapentacyclo[9.4.2.01,12.05,15.08,12]heptadecane-17-carboxylate Chemical class C1C[C@@]2(O)C(=O)C[C@@H]3[C@]22OC[C@]4(CCC(=O)CC)[C@H]1CN(C)C[C@@]42C[C@H]3C(=O)OC BNSQPPYRCUIFLZ-LSLDVNGTSA-N 0.000 title claims abstract description 59
- 208000033626 Renal failure acute Diseases 0.000 title claims abstract description 35
- 201000011040 acute kidney failure Diseases 0.000 title claims abstract description 35
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims abstract description 34
- 208000012998 acute renal failure Diseases 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title abstract description 13
- 229940079593 drug Drugs 0.000 title abstract description 4
- 241001597008 Nomeidae Species 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000008327 renal blood flow Effects 0.000 claims description 4
- 210000002966 serum Anatomy 0.000 claims description 4
- 230000000630 rising effect Effects 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 241000700159 Rattus Species 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000003907 kidney function Effects 0.000 description 5
- 229950002366 nafoxidine Drugs 0.000 description 5
- ONQBOTKLCMXPOF-UHFFFAOYSA-N 1-ethylpyrrolidine Chemical compound CCN1CCCC1 ONQBOTKLCMXPOF-UHFFFAOYSA-N 0.000 description 4
- 208000035126 Facies Diseases 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000010255 intramuscular injection Methods 0.000 description 4
- 239000007927 intramuscular injection Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000208664 Daphniphyllum Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229930186810 daphmalenine Natural products 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 210000005084 renal tissue Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 208000001889 Acid-Base Imbalance Diseases 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 201000003126 Anuria Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 206010030302 Oliguria Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
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- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
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- 150000002611 lead compounds Chemical class 0.000 description 1
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- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of organic synthesis and pharmaceutical chemistry and particularly relates to a derivative of Daphmalenine A, a preparation method for the derivative of Daphmalenine A and application of the derivative of Daphmalenine A in the preparation of acute renal failure resisting drugs. According to the invention, a novel derivative of Daphmalenine A is synthesized, and a preparation method of the derivative of Daphmalenine A is disclosed. Shown by pharmacological experiments, the derivative of Daphmalenine A, disclosed by the invention, has an acute renal failure resisting effect and has a value in the development of the acute renal failure resisting drugs.
Description
Technical field
The present invention relates to organic synthesis and medicinal chemistry art, be specifically related to Daphmalenine A derivant, preparation method and its usage.
Background technology
Acute renal failure (Acute Renal Failure, ARF) be the clinical syndrome caused by many reasons, be found in clinical departments patient, sickness rate is high and often have serious consequences, its feature is that (a few hours are to a couple of days) renal function sharply declines in a short time, clinical manifestation is acute oliguria (urine volume <400mLPd) or anuria (urine volume <100mLPd), in body, nitrogen matter metabolite is discharged and is produced obstacle, there is azotemia rapidly, water and electrolyte, acid base imbalance, and cause each system corresponding function imbalance of whole body.The principal element of acute renal failure is caused to be the sharply minimizing of renal blood flow, and the oxidative stress caused due to nephridial tissue ischemia and cell injury, finally cause the deterioration of renal tissue structural damage and function.There is no the generally acknowledged effective medicine for the treatment of acute renal failure clinically at present, only by correcting water-electrolyte balance, correcting the symptomatic treatment measures such as acidosis and improving symptom, the later stage also needs to maintain body function by hemodialysis.Improving kidney perfusion obstacle and alleviating in Renal tissues damage and have the clinical medicine of obvious curative effects rare.
From natural product, find compound or lead compound and carry out structural modification and obtain its derivant, thus the potential drug obtaining high-efficiency low-toxicity there is important value most.
The Compound D aphmalenine A that the present invention relates to is one and within 2011, delivers (Yu Zhang et al., 2011.Daphmalenines A and B:Two New Alkaloids with Unusual Skeletons from Daphniphyllum himalense.Eur.J.Org.Chem.2011,4103 – 4107) compound, we have carried out structural modification to Compound D aphmalenine A, obtain a new Daphmalenine A derivant, and its anti-acute renal failure activity is evaluated, it is active that it has anti-acute renal failure.
Summary of the invention
The invention discloses a Daphmalenine A derivant, its structure is:
Daphmalenine A derivant (III) of the present invention is by method preparation below:
(1) Daphmalenine A (I) and glycol dibromide are obtained by reacting the O-bromoethyl derivant (II) of Daphmalenine A;
(2) O-bromoethyl derivant (II) and the pyrrolidine generation substitution reaction of Daphmalenine A obtain O-(nafoxidine base) ethyl derivative (III) of Daphmalenine A.
The preparation method of the O-(nafoxidine base) ethyl derivative (III) of further Daphmalenine A is:
(1) 419mg Compound D aphmalenine A (I) is dissolved in 10mL benzene, in solution, adds the tetrabutyl ammonium bromide of 0.08g, the glycol dibromide of 7.520g and 50% sodium hydroxide solution of 6mL; Mixture stirs 12h at 35 degrees Celsius; After 12h, reactant liquor is poured in frozen water, use dichloromethane extraction twice immediately, merge organic phase solution; Then use water and saturated common salt water washing 4 times successively to organic phase solution, then use anhydrous sodium sulfate drying, last concentrating under reduced pressure is removed solvent and is obtained product crude product; Product crude product purification by silica gel column chromatography, mobile phase is: petroleum ether/acetone=100:1.5, v/v, collects the yellow yellow solid concentrating elution band namely to obtain the O-bromoethyl derivant (II) of Daphmalenine A.
(2) the O-bromoethyl derivant (II) of the Daphmalenine A of 263mg is dissolved in the middle of 20mL acetonitrile, adds the Anhydrous potassium carbonate of 345mg wherein, the potassium iodide of 84mg and the pyrrolidine of 2840mg, mixture reflux 12h; After reaction terminates, reactant liquor is poured in 20mL frozen water, with equivalent dichloromethane extraction four times, merge organic facies; Organic facies after merging with water and saturated common salt water washing successively, then use anhydrous sodium sulfate drying, concentrating under reduced pressure is removed solvent and is obtained product crude product; Product crude product purification by silica gel column chromatography, mobile phase is: petroleum ether/acetone=100:1.5, v/v, collects the brown gummy solid 183.2mg that namely brown concentrated elution band obtains the O-(nafoxidine base) ethyl derivative (III) of Daphmalenine A.
Compound III disclosed by the invention can make pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
The object of this invention is to provide the purposes that Daphmalenine A derivant (III) is used for the treatment of acute renal failure, namely for the preparation of the purposes for the treatment of acute renal failure medicine.
Daphmalenine A derivant (III) of the present invention has obvious therapeutical effect to acute renal failure disease.
Find that Daphmalenine A derivant (III) can improve the function of kidney by our research.
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by any restriction of specific embodiment, but be limited by claim.
Detailed description of the invention
The preparation of embodiment 1 Compound D aphmalenine A
Document (the Yu Zhang et al. that the people such as the preparation method reference Yu Zhang of Compound D aphmalenine A (I) deliver, 2011.Daphmalenines A and B:Two New Alkaloids with Unusual Skeletons from Daphniphyllum himalense.Eur.J.Org.Chem.2011,4103 – 4107) method.
The synthesis of the O-bromoethyl derivant (II) of embodiment 2 Daphmalenine A
By Compound I (419mg, 1.00mmol) be dissolved in 10mL benzene, add in solution tetrabutyl ammonium bromide (TBAB) (0.08g), 1,50% sodium hydroxide solution of 2-Bromofume (7.520g, 40.00mmol) and 6mL.Mixture stirs 12h at 35 degrees Celsius.After 12h, reactant liquor is poured in frozen water, use dichloromethane extraction twice immediately, merge organic phase solution.Then use water and saturated common salt water washing 4 times successively to organic phase solution, then use anhydrous sodium sulfate drying, last concentrating under reduced pressure is removed solvent and is obtained product crude product.Product crude product purification by silica gel column chromatography (mobile phase is: petroleum ether/acetone=100:1.5, v/v), collects the yellow yellow solid (320mg, 61%) concentrating elution band namely to obtain Compound II per.
1H NMR(500MHz,DMSO-d
6)δ3.84(d,J＝1.6Hz,2H),3.76–3.50(m,5H),3.42(s,2H),3.09(s,1H),2.99(s,1H),2.88(s,1H),2.70(s,1H),2.64(d,J＝19.1Hz,3H),2.45(d,J＝5.6Hz,3H),2.33(s,1H),2.19–2.12(m,5H),2.07(s,1H),1.97(d,J＝9.2Hz,3H),1.84–1.76(m,3H),1.69(s,1H),1.15(s,1H),1.04(s,3H)。
13C NMR(125MHz,DMSO-d6)δ219.71(s),211.07(s),176.65(s),66.24(s),65.38(s),63.59(s),59.42(s),54.79(s),52.18(s),46.22(s),46.01(s),45.50(s),45.27(s),40.33(s),37.86(s),37.61(s),36.27(s),34.26(s),30.89(s),28.52(s),26.04(s),25.24(s),8.50(s)。
HRMS(ESI)m/z[M+H]
+calcd for C
25H
37BrNO
6:526.1804；found 526.1801.
The synthesis of the O-(nafoxidine base) ethyl derivative (III) of embodiment 3 Daphmalenine A
Compound II per (263mg, 0.5mmol) is dissolved in the middle of 20mL acetonitrile, adds Anhydrous potassium carbonate (345mg wherein, 2.5mmol), potassium iodide (84mg, 0.5mmol) and pyrrolidine (2840mg, 40mmol), mixture reflux 12h.After reaction terminates, reactant liquor is poured in frozen water, with equivalent dichloromethane extraction four times, merge organic facies.Organic facies after merging with water and saturated common salt water washing successively, then use anhydrous sodium sulfate drying, concentrating under reduced pressure is removed solvent and is obtained product crude product.(mobile phase is product crude product purification by silica gel column chromatography: petroleum ether/acetone=100:1.5, v/v), collect the brown gummy solid (183.2mg, 71%) that namely brown concentrated elution band obtains the O-(nafoxidine base) ethyl derivative (III) of Daphmalenine A.
1H NMR(500MHz,DMSO-d6)δ3.80(s,1H),3.71(s,3H),3.50(s,2H),3.14(s,1H),3.06(s,1H),2.86(s,1H),2.73(d,J＝2.7Hz,2H),2.67(d,J＝5.3Hz,4H),2.55(s,4H),2.53–2.36(m,4H),2.21–2.15(m,5H),2.16–1.86(m,4H),1.85(d,J＝7.5Hz,2H),1.78(s,1H),1.72(d,J＝10.7Hz,5H),1.14(s,1H),1.08(s,3H)。
13C NMR(125MHz,DMSO-d6)δ219.76(s),211.10(s),176.66(s),66.23(s),63.55(s),61.51(s),59.41(s),54.83(s),54.50(s),53.87(s),52.18(s),46.20(s),46.04(s),45.53(s),45.24(s),40.32(s),37.87(s),37.64(s),36.26(s),30.85(s),28.50(s),25.95(s),25.18(d,J＝8.8Hz),8.42(s)。
HRMS(ESI):m/z[M+H]
+calcd for C
29H
45N
2O
6:517.3278；found:517.3271。
Embodiment 4 compound III is to the therapeutical effect of acute renal failure rat
(1) experimental technique
Intramuscular injection glycerol is adopted to cause Acute Renal Failure Rats animal model.Select the healthy male SD rat 30 of 180 ~ 220g, be divided into 5 groups at random: sham operated rats (intramuscular injection normal saline); Model group (intramuscular injection glycerol); Administration intervention group (compound III, Compound I or pyrrolidine 0.6mg/Kg, intramuscular injection glycerol), each group rat tail vein injection saline or medicine immediately after glycerol modeling, be administered once after 12 and 24 hours again.
1-ethyl pyrrolidine (compound IV) is commercially available analytical pure.
(2) observation index
Metabolic cage collection twenty-four-hour urine is put into after the administration of rat last or normal saline, stay latter 6 hours of urine with 4% chloral hydrate intraperitoneal injection of anesthesia, adopt laser Doppler flowmetry to measure after modeling and bilateral renal blood flow after treatment, average as single animal renal blood flow; Get blood and prepare serum, measure blood BUN and Cre (all by the operation of test kit description).
(3) experimental result
1. compound III can increase acute renal failure Mouse Kidney blood flow
Compound III significantly can increase acute renal failure Mouse Kidney blood flow, and Compound I and 1-ethyl pyrrolidine act on without this.
Table 1 compound III is on the impact of acute renal failure Mouse Kidney blood flow
* P<0.05vs acute renal failure model group
2. compound III is to the protective effect of acute renal failure Mouse Kidney function tool
Acute renal failure rat intravenous injection normal saline is after 24 hours, and serum BUN and Cre is in table 2.Acute renal failure model group, apparently higher than sham operated rats, illustrates that model group animal renal function injury is serious.Compound III can improve the renal function (P<0.05) of acute renal failure rat, and Compound I and 1-ethyl pyrrolidine act on without this.
In table 2.
The each rats in test groups renal function index of table 2 compares
* P<0.05vs acute renal failure model group
Conclusion: compound III can protect the function of kidney, can be used for preparing anti-acute renal failure medicine.And Compound I and 1-ethyl pyrrolidine can not protect kidney, be not available to prepare anti-acute renal failure medicine.
The preparation of embodiment 5 compound III tablet involved in the present invention
Get the one in the middle of 20 g of compound III or its pharmaceutically acceptable salt, add the customary adjuvant 180 grams preparing tablet, mixing, conventional tablet presses makes 1000.
The preparation of embodiment 6 compound III capsule involved in the present invention
Get the one in the middle of 20 g of compound III or its pharmaceutically acceptable salt, add prepare capsule customary adjuvant as starch 180 grams, mixing, encapsulatedly makes 1000.
Claims (4)
1. one kind has Daphmalenine A derivant (III) and the application of pharmaceutically acceptable salt in treatment acute renal failure medicine thereof of structure shown in formula III:
。
2. a kind of Daphmalenine A derivant (III) and the application of pharmaceutically acceptable salt in treatment acute renal failure medicine thereof with structure shown in formula III as claimed in claim 1, is characterized by: Daphmalenine A derivant (III) improves the reduction of the renal blood flow amount caused by acute renal failure.
3. a kind of Daphmalenine A derivant (III) and the application of pharmaceutically acceptable salt in treatment acute renal failure medicine thereof with structure shown in formula III as claimed in claim 1, is characterized by: Daphmalenine A derivant (III) improves the rising of the serum BUN that acute renal failure causes.
4. a kind of Daphmalenine A derivant (III) and the application of pharmaceutically acceptable salt in treatment acute renal failure medicine thereof with structure shown in formula III as claimed in claim 1, is characterized by: Daphmalenine A derivant (III) improves the rising of the change of serum C re that acute renal failure causes.
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| CN102861008A (en) * | 2012-10-25 | 2013-01-09 | 南京大学 | Application of Aphanamixoid A in medicine for treating acute renal failure |
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| CN103127151A (en) * | 2012-10-26 | 2013-06-05 | 吴俊华 | Application of Gypensapogenin A in medicines treating acute renal failure |
| CN103251637A (en) * | 2013-06-03 | 2013-08-21 | 南京正亮医药科技有限公司 | Application of Polyflavanostilbene A in preparing medicine for treating acute renal failure |
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Application publication date: 20150722 |