CN104095856A - Application of diethylamine derivative of Cleistanone in preparation of medicine resistant to acute renal failure - Google Patents
Application of diethylamine derivative of Cleistanone in preparation of medicine resistant to acute renal failure Download PDFInfo
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- renal failure
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- XURLTFUKDPZAPN-QFIPXVFZSA-N Cleistanone Natural products O(C)[C@H]1OC(=O)c2c(-c3cc4OCOc4cc3)c3c(c(O)c12)cc(OC)c(OC)c3 XURLTFUKDPZAPN-QFIPXVFZSA-N 0.000 title claims abstract description 37
- 208000033626 Renal failure acute Diseases 0.000 title claims abstract description 33
- 201000011040 acute kidney failure Diseases 0.000 title claims abstract description 33
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims abstract description 32
- 208000012998 acute renal failure Diseases 0.000 title claims abstract description 32
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 125000001664 diethylamino group Chemical class [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 title 1
- GEIFQLXIDUDMNZ-PCJVTFPHSA-N (4aR,4bR,6aR,8S,10aR,10bR,12R,12aR)-12-hydroxy-1,1,1',1',4a,10a,10b-heptamethyl-3'-methylidenespiro[3,4,4b,5,6,6a,7,9,10,11,12,12a-dodecahydrochrysene-8,2'-cyclopentane]-2-one Chemical class CC1(C)CCC(=C)[C@@]11C[C@@H](CC[C@H]2[C@]3(C[C@@H](O)[C@H]4C(C)(C)C(=O)CC[C@@]42C)C)[C@@]3(C)CC1 GEIFQLXIDUDMNZ-PCJVTFPHSA-N 0.000 claims abstract description 38
- 241000785597 Cleistanthus Species 0.000 claims description 32
- 150000002576 ketones Chemical class 0.000 claims description 30
- 239000002023 wood Substances 0.000 claims description 30
- 241001597008 Nomeidae Species 0.000 claims description 24
- 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
- 238000002474 experimental method Methods 0.000 abstract description 2
- 238000003786 synthesis reaction 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 15
- 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
- 150000001875 compounds Chemical class 0.000 description 11
- 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
- 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
- 239000000203 mixture Substances 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 230000006870 function Effects 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 230000003907 kidney function Effects 0.000 description 5
- 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
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 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
- 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
- 230000006378 damage Effects 0.000 description 3
- 230000000694 effects 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
- XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 238000000034 method 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
- 230000002194 synthesizing effect Effects 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
- 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
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 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
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the fields of organic synthesis and medicinal chemistry and particularly to a derivative of Cleistanone, the preparation method for the derivative of the Cleistanone and the usage of the derivative of Cleistanone in preparing medicine resistant to acute renal failure. According to the invention, a novel derivative of the Cleistanone is synthesized and the preparation method for the novel derivative of the Cleistanone is disclosed. Pharmacological experiments indicate that the derivative of the Cleistanone provided by the invention has the function of resisting the acute renal failure and has the value of developing medicine resistant to the acute renal failure.
Description
Technical field
The present invention relates to organic synthesis and pharmaceutical chemistry field, be specifically related to Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant, preparation method and its usage.
Background technology
Acute renal failure (Acute Renal Failure, ARF) be the clinical syndrome being caused by many reasons, be found in clinical departments patient, sickness rate is high and often have serious consequences, for in a short time, (a few hours are to a couple of days) renal function sharply declines its feature, clinical manifestation is acute oliguria (urine amount <400mLPd) or anuria (urine amount <100mLPd), in body, nitrogen matter metabolite is discharged and is produced obstacle, there is rapidly azotemia, water and electrolyte, acid base imbalance, and cause the imbalance of the each system corresponding function of whole body.The principal element that causes acute renal failure is the sharply minimizing of renal blood flow, and the oxidative stress and the cell injury that cause due to nephridial tissue ischemia, finally causes the deterioration of renal tissue structural damage and function.There is no clinically at present the generally acknowledged effective medicine for the treatment of acute renal failure, only can, by correcting water-electrolyte balance, correct the symptomatic treatment measures such as acidosis and improve symptom, the later stage also needs to maintain body function by hemodialysis.There is the clinical medicine of obvious curative effects rare improving kidney perfusion obstacle and alleviate aspect Renal tissues damage.
From natural product, find compound or lead compound and carry out structural modification and obtain its derivant, thereby the potential drug that obtains high-efficiency low-toxicity there is important value most.
The compound Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone the present invention relates to is one and within 2011, delivers (Van Trinh Thi Thanh et al., 2011.Cleistanone:A Triterpenoid from Cleistanthus indochinensis with a New Carbon Skeleton.
volume 2011, Issue22,pages4108 – 4111, August 2011) compound, we have carried out structural modification to compound Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone, obtain a new Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant, and its anti-acute renal failure activity is evaluated, it has anti-acute renal failure activity.
Summary of the invention
The invention discloses a Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant, its structure is:
Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant of the present invention (III) can be passed through method preparation below:
(1) Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone (I) reacts the O-bromoethyl derivant (II) that obtains Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone with glycol dibromide;
(2) the O-bromoethyl derivant (II) of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone makes Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) with diethylamine generation substitution reaction.
Further the preparation method of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) is:
(1) 440mg compound Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone (I) is dissolved in to 10mL benzene, to the tetrabutyl ammonium bromide that adds 0.04g in solution, 50% sodium hydroxide solution of the glycol dibromide of 3.760g and 6mL; Mixture stirs 24h at 25 degrees Celsius; After 24h, reactant liquor is poured in frozen water, used immediately dichloromethane extraction twice, merge organic phase solution; Then to organic phase solution successively water and saturated common salt water washing 3 times, 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, v/v, collects the yellow yellow solid of concentrating elution band to obtain the O-bromoethyl derivant (II) of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone.
(2) the O-bromoethyl derivant of the Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone of 273mg is dissolved in the middle of 20mL acetonitrile, adds wherein the Anhydrous potassium carbonate of 345mg, the potassium iodide of 84mg and the diethylamine of 1460mg, mixture reflux 8h; After reaction finishes, reactant liquor is poured in frozen water, used equivalent dichloromethane extraction three times, merge organic facies; Water and saturated common salt water washing merge organic facies afterwards successively, then use anhydrous sodium sulfate drying, and concentrating under reduced pressure is removed solvent and obtained product crude product; Product crude product purification by silica gel column chromatography, mobile phase is: petroleum ether/acetone=100:1, v/v, collects faint yellow concentrated elution band and obtain the faint yellow gluey solid of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III).
Compound disclosed by the invention can be made pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
The object of this invention is to provide the purposes that Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) is used for the treatment of acute renal failure, for the preparation of the purposes for the treatment of acute renal failure medicine.
Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant of the present invention (III) has obvious therapeutical effect to acute renal failure disease.
Can improve the function of kidney by our research discovery Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subject to any restriction of specific embodiment, but be limited by claim.
Detailed description of the invention
The preparation of embodiment 1 compound Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone
Document (the Van Trinh Thi Thanh et al. that the preparation method of compound Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone (I) is delivered with reference to people such as Van Trinh Thi Thanh, 2011.Cleistanone:A Triterpenoid from Cleistanthus indochinensis with a New Carbon Skeleton.Volume 2011, Issue 22, pages 4108 – 4111, August 2011) method.
Synthesizing of the O-bromoethyl derivant (II) of embodiment 2 Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone
By Compound I (440mg, 1.00mmol) be dissolved in 10mL benzene, in solution, add tetrabutyl ammonium bromide (TBAB) (0.04g), 1,50% sodium hydroxide solution of 2-Bromofume (3.760g, 20.00mmol) and 6mL.Mixture stirs 24h at 25 degrees Celsius.After 24h, reactant liquor is poured in frozen water, used immediately dichloromethane extraction twice, merge organic phase solution.Then to organic phase solution successively water and saturated common salt water washing 3 times, then use anhydrous sodium sulfate drying, last concentrating under reduced pressure is removed solvent and is obtained product crude product.Product is purification by silica gel column chromatography (mobile phase is: petroleum ether/acetone=100:1, v/v) for crude product, collects the yellow yellow solid (344mg, 63%) of concentrating elution band to obtain Compound I I.
1H?NMR(500MHz,DMSO-d
6)δ5.04(s,1H),4.82(s,1H),3.94(d,J＝26.5Hz,1H),3.87(d,J＝26.5Hz,2H),3.57(s,2H),2.40(d,J＝14.0Hz,1H),2.39(d,J＝14.0Hz,1H),2.27(s,1H),2.21(s,1H),2.15(s,1H),1.82(s,1H),1.62(s,2H),1.57(d,J＝3.3Hz,1H),1.54(d,J＝3.3Hz,1H),1.50(d,J＝1.2Hz,1H),1.47(d,J＝1.2Hz,1H),1.39(d,J＝15.3Hz,2H),1.34(d,J＝15.3Hz,1H),1.26(dd,J＝32.6,13.7Hz,4H),1.13(d,J＝18.0Hz,2H),1.05(s,6H),0.98(s,1H),0.88(s,12H),0.78(s,3H),0.74(s,1H)。
13C?NMR(125MHz,DMSO-d6)δ216.59(s),154.50(s),105.23(s),74.63(s),69.85(s),59.71(s),52.55(s),51.21(s),47.92(s),44.10(s),42.25(s),41.73(s),40.64(s),40.16(s),38.88(s),38.65(s),37.21(s),36.23(s),33.34(d,J＝1.1Hz),32.96(s),29.91(s),27.18(s),26.03(s),24.23(s),23.96(s),20.77(s),18.48(s),17.98(s),16.93(s)。
HRMS(ESI)m/z[M+H]
+calcd?for?C
32H
52BrO
2:547.3151；found547.3159.
Synthesizing of O-(diethylin) ethyl derivative (III) of embodiment 3 Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone
Compound I I (273mg, 0.5mmol) is dissolved in the middle of 20mL acetonitrile, adds wherein Anhydrous potassium carbonate (345mg, 2.5mmol), potassium iodide (84mg, 0.5mmol) and diethylamine (1460mg, 20mmol), mixture reflux 8h.After reaction finishes, reactant liquor is poured in frozen water, used equivalent dichloromethane extraction three times, merge organic facies.Water and saturated common salt water washing merge organic facies afterwards successively, then use anhydrous sodium sulfate drying, and concentrating under reduced pressure is removed solvent and obtained product crude product.Product is purification by silica gel column chromatography (mobile phase is: petroleum ether/acetone=100:1, v/v) for crude product, collects the faint yellow gluey solid (169.8mg, 63%) that faint yellow concentrated elution band obtains compound III.
1H?NMR(500MHz,DMSO-d6)δ5.04(s,1H),4.85(s,1H),4.37(s,1H),3.54(s,2H),2.91(s,4H),2.64(s,2H),2.41(d,J＝17.2Hz,2H),2.30(s,1H),2.21(d,J＝22.5Hz,2H),1.82(s,1H),1.65(s,2H),1.58(d,J＝9.0Hz,2H),1.49(d,J＝5.7Hz,2H),1.39(d,J＝13.4Hz,3H),1.36–1.28(m,3H),1.28–1.26(m,1H),1.26–1.14(m,8H),1.06(s,6H),0.92(d,J＝19.4Hz,13H),0.82(s,3H),0.71(s,1H).
13C?NMR(125MHz,DMSO-d6)δ216.59(s),154.50(s),105.23(s),74.65(s),66.82(s),59.77(s),52.54(d,J＝3.0Hz),51.21(s),47.92(s),47.73(s),44.13(s),42.30(s),41.77(s),40.65(s),40.17(s),38.86(s),38.68(s),37.26(s),36.27(s),33.35(s),32.97(s),29.89(s),27.21(s),26.08(s),24.27(s),23.97(s),20.78(s),18.46(s),18.01(s),16.98(s),12.33(s).
HRMS(ESI):m/z[M+H]
+calcd?for?C
36H
62NO
2:540.4781；found:540.4787。
The therapeutical effect of embodiment 4 compound III to acute renal failure rat
(1) experimental technique
Adopt intramuscular injection glycerol to cause Acute Renal Failure Rats animal model.Select 30 of the healthy male SD rats of 180～220g, be divided at random 3 groups: sham operated rats (intramuscular injection normal saline); Model group (intramuscular injection glycerol); Compound III group (compound III 0.6mg/Kg, intramuscular injection glycerol), respectively organizes rat tail vein injection saline or compound III immediately after glycerol modeling, after 12 and 24 hours, is administered once again.
(2) observation index
Rat last gives to put into metabolic cage collection twenty-four-hour urine after compound III or normal saline, stay latter 6 hours of urine with 4% chloral hydrate intraperitoneal injection of anesthesia, adopt laser Doppler flowmetry to measure bilateral renal blood flow after modeling and 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
The impact of table 1 compound III on 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 are 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 be improved the renal function (P<0.05) of acute renal failure rat.In table 2.
The comparison of the each rats in test groups renal function index of table 2
* P<0.05vs acute renal failure model group
Conclusion: compound III can be protected the function of kidney, can be used for preparing 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 grams of compound III or its pharmaceutically acceptable salt, add 180 grams of conventional adjuvants preparing tablet, mix, conventional tablet machine is made 1000.
The preparation of embodiment 6 compound III capsule involved in the present invention
Get the one in the middle of 20 grams of compound III or its pharmaceutically acceptable salt, add the conventional adjuvant of preparing capsule as 180 grams of starch, mix, encapsulatedly make 1000.
Claims (4)
1. one kind has Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone 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 Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone 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: Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) is improved the reduction of the caused renal blood flow amount of acute renal failure.
3. a kind of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) with structure shown in formula III as claimed in claim 1 and the application of pharmaceutically acceptable salt in treatment acute renal failure medicine thereof, is characterized by: Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) is improved the rising of the serum BUN that acute renal failure causes.
4. a kind of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) with structure shown in formula III as claimed in claim 1 and the application of pharmaceutically acceptable salt in treatment acute renal failure medicine thereof, is characterized by: Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone derivant (III) is improved the rising of the change of serum C re that acute renal failure causes.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666310A (en) * | 2015-03-10 | 2015-06-03 | 南京大学 | Application of O-(triazolyl) ethyl derivative of Cleistanone in preparation of medicine resistant to acute renal failure |
| CN104784190A (en) * | 2015-04-29 | 2015-07-22 | 南京大学 | Application of O-(benzimidazolyl) ethyl derivative of cleistanone in preparation of medicine for resisting acute renal failure |
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Non-Patent Citations (2)
| Title |
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| VAN TRINH THI THANH, ET AL.: "Cleistanone: A Triterpenoid from Cleistanthus indochinensis with a New Carbon Skeleton", 《EUR. J. ORG. CHEM.》, 7 June 2011 (2011-06-07), pages 4108 - 4111 * |
| 朱少铭 等: "甘草酸二铵防治心脏手术患者肾损伤72例", 《医药导报》, vol. 23, no. 9, 30 September 2004 (2004-09-30), pages 626 - 627 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666310A (en) * | 2015-03-10 | 2015-06-03 | 南京大学 | Application of O-(triazolyl) ethyl derivative of Cleistanone in preparation of medicine resistant to acute renal failure |
| CN104784190A (en) * | 2015-04-29 | 2015-07-22 | 南京大学 | Application of O-(benzimidazolyl) ethyl derivative of cleistanone in preparation of medicine for resisting acute renal failure |
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