CN104127421A - Application of O-(piperidyl)ethyl derivative of Cleistanone in preparation of anti-low erythrocyte anemia drugs - Google Patents
Application of O-(piperidyl)ethyl derivative of Cleistanone in preparation of anti-low erythrocyte anemia drugs Download PDFInfo
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- CN104127421A CN104127421A CN201410375041.9A CN201410375041A CN104127421A CN 104127421 A CN104127421 A CN 104127421A CN 201410375041 A CN201410375041 A CN 201410375041A CN 104127421 A CN104127421 A CN 104127421A
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- Prior art keywords
- piperidyl
- anemia
- cleistanone
- ethyl derivative
- muell
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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 45
- 208000007502 anemia Diseases 0.000 title claims abstract description 45
- 210000003743 erythrocyte Anatomy 0.000 title claims abstract description 23
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 229940079593 drug Drugs 0.000 title abstract description 4
- 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 compound 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 description 34
- 241000785597 Cleistanthus Species 0.000 claims description 27
- 150000002576 ketones Chemical class 0.000 claims description 25
- 239000002023 wood Substances 0.000 claims description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
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- -1 phosphate amine Chemical class 0.000 claims description 5
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
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- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 4
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of organic synthesis and medicinal chemistry, and in particular relates to an O-(piperidyl)ethyl derivative of Cleistanone, a preparation method thereof and application in preparation of anti-low erythrocyte anemia drugs. The invention synthesizes a new O-(piperidyl)ethyl derivative of Cleistanone and discloses its preparation method. Pharmacological experiments show that the O-(piperidyl)ethyl derivative of Cleistanone provided by the invention has an anti-low erythrocyte anemia effect, and has the value of developing anti-low erythrocyte anemia drugs.
Description
Technical field
The present invention relates to organic synthesis and pharmaceutical chemistry field, be specifically related to O-(piperidyl) ethyl derivative, the preparation method and its usage of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone.
Background technology
Clinical characters based on different, anemia has different classification.As: by anemia tempo, divide acute and chronic anemia; Red by bone marrow is hypertrophy situation minute hyperplastic anemia (as hemolytic anemia, iron deficiency anemia, megaloblastic anemia etc.) and Hypolasia anemia (as aplastic anemia).
The normal classification from anemia pathogenesis and the cause of disease clinically:
1. erythropoiesis reduces property anemia
The anomalous effects erythropoiesis of hematopoietic cell, bone marrow hematogenesis microenvironment and hemopoietic raw material, can form erythropoiesis minimizing property anemia.
(1) hematopoietic stem/progenitor cells caused by abnormal anemia
1) aplastic anemia (AA) AA is a kind of marrow hematopoiesis function failure disease, relevant with the hematopoietic stem/progenitor cells infringement of secondary with former.The pathogenesis of part pancytopenia and B cell produce anti-medullary cell autoantibody, and then destroy or to suppress myeloid element relevant.
2) pure red cell aplasia anemia (PRCA) PRCA refers to that bone marrow erythroid hematopoiesis stem/progenitor cells suffers damage, and then causes anemia.According to the cause of disease, this disease can be divided into congenital and posteriority two classes.Congenital PRCA is Diamond-Blackfan syndrome, is due to heredity; Posteriority PRCA comprises former, secondary two classes.There is scholar to find in part constitutional PRCA patients serum, have self EPO or normoblast antibody.Secondary cases PRCA mainly contains medicine relationship type, infects relationship type (antibacterial and virus, as piconavirus B19, hepatitis virus etc.), autoimmune disease relationship type, lymphopoiesis disease association type (as thymoma, lymphoma, plasma cell dyscrasia and Lymphocytic leukemia etc.) and acute aplastic crisis etc.
3) congenital dyserythropoietic anemia (CDA) CDA be a class heritability red be the optimum clone's caused by abnormal of stem/progenitor cells, take the red refractory anemia that is ineffective hematopoiesis and paramophia and is feature.According to mode of inheritance, this disease can be divided into the hidden flight of steps leading to a palace hall genotype of autosome and dominant inheritance's type.
4) there is the abnormal of matter in these disease hematopoietic stem/progenitor cells of hemopoietic system malignant clone disease, comprises that myelodysplastic syndrome and all kinds of hematopoietic system cancer disease are as leukemia etc.The former is because DH, high hypertrophy, and, there is hemolysis in situ in high apoptosis; The latter's neoplastic hyperplasia, low apoptosis and low differentiation, hemopoietic regulates and to be also affected, thereby makes normal mature erythrocytopenia and anemia occurs.
(2) hematopoieticmicroenviron-ment caused by abnormal anemia
Hematopoieticmicroenviron-ment comprises bone marrow matrix, stromal cell and cytokine.
1) the impaired Anemia BMN of bone marrow matrix and stromal cell, myelofibrosis, myelosclerosis, marble bone marrow sick, various extramedullary tumor diseases shift and various infection or non-infectious osteomyelitis, all can be because of damage bone marrow matrix and stromal cell, there is extremely to affect hemopoietic in hematopoieticmicroenviron-ment.
2) hemopoietic regulatory factor horizontal abnormality Anemia stem cell factor (SCF), interleukin (IL), grain-monosystem colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), erythropoietin (EPO), thrombopoietin (TPO), PDGF (TGF), tumor necrosis factor (TNF) and interferon (IFN) etc. all have positive negative regulation hemoposieis.When renal insufficiency, hepatopathy and hypophysis or hypothyroidism etc., produce EPO deficiency; Neoplastic disease or some viral infection can induce body to produce more hemopoietic negative regulatory factor as TNF, IFN, inflammatory factor etc., all can cause ACD (ACD).
(3) hemopoietic insufficient raw material or utilize obstacle Anemia
Hemopoietic raw material refers to hematopoietic cell proliferation, differentiation, the necessary material of metabolism, as protein, lipid, vitamin (folic acid, vitamin B12 etc.), trace element (ferrum, copper, zinc etc.) etc.Any hemopoietic insufficient raw material or utilize obstacle all may cause erythropoiesis to reduce.
1) folic acid or vitamin B12 deficiency or the megaloblastic anemia that utilizes obstacle Anemia to cause body folic acid or vitamin B12 definitely or relatively to lack or utilize obstacle to cause due to various physiology or pathological factor.
2) iron deficiency and ferrum utilize aplastic anemia this are modal anemias clinically.It is synthetic that iron deficiency and ferrum utilize obstacle to affect haemachrome, and having such anemia of title is haemachrome resulting anomaly anemia.The red cell morphology of such anemia diminishes, and central olistherozone expands, and belongs to microcytic hypochromic anemia.
2. hemolytic anemia (HA)
It is the too much property of hematoclasis anemia.
3. hemorrhagic anemia
According to the speed of losing blood, divide acutely and chronic, chronic blood loss anemia often merges iron deficiency anemia.Can be divided into disorders of blood coagulation (as idiopathic thrombocytopenic purpura, hemophilia and serious hepatopathy etc.) non-two classes due to disorders of blood coagulation (as wound, tumor, tuberculosis, bronchiectasis, peptic ulcer, hemorrhoid and gynaecopathia etc.) that go out of making peace.
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 has important value.
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.
volume2011, Issue22,pages4108 – 4111, August2011) compound, we have carried out structural modification to compound Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone, obtained O-(piperidyl) ethyl derivative of a new Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone, and the low property of its anti-erythrocyte anemia activity is evaluated, it is active that it has the low property of anti-erythrocyte anemia.
Summary of the invention
O-(piperidyl) ethyl derivative that the invention discloses a Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone, its structure is:
O-(piperidyl) ethyl derivative (III) of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr of the present invention wood ketone Cleistanone can be prepared by method 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 and piperidines generation substitution reaction make O-(piperidyl) ethyl derivative (III) of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone.
Further the preparation method of O-(piperidyl) ethyl derivative (III) of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone 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 (II) 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 piperidines of 852mg, mixture reflux 16h; After reaction finishes, reactant liquor is poured in 20mL 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=100:0.5, v/v, collects the yellow yellow colloidal solid 157.0mg that concentrates elution band to obtain O-(piperidyl) ethyl derivative (III) of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone.
Compound disclosed by the invention can be made pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
The object of the present invention is to provide the new application of the compounds of this invention in pharmaceutical field.
The present invention relates to the compounds of this invention as the application in the low property of preparation treatment erythrocyte anemia medicine.
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.
The specific embodiment
The preparation of embodiment 1 compound Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone
Document (Van Trinh Thi Thanh et al., 2011.Cleistanone:A Triterpenoid from Cleistanthus indochinensis with a New Carbon Skeleton. 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
volume2011, Issue22,pages4108 – 4111, method August2011).
Synthesizing of the O-bromoethyl derivant (II) of embodiment 2 Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone
Compound I (440mg, 1.00mmol) is dissolved in to 10mL benzene, in solution, adds tetrabutyl ammonium bromide (TBAB) (0.04g), 50% sodium hydroxide solution of glycol dibromide (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.(mobile phase is product purification by silica gel column chromatography for crude product: petroleum ether/acetone=100:1, v/v), collect 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-(piperidyl) 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 piperidines (852mg, 10mmol), mixture reflux 16h.After reaction finishes, reactant liquor is poured in 20mL 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 for crude product purification by silica gel column chromatography (mobile phase is: petroleum ether/acetone=100:0.5, v/v), collect the yellow yellow colloidal solid (157.0mg, 57%) of concentrating elution band to obtain O-(piperidyl) ethyl derivative of Cleistanone.
1H?NMR(500MHz,DMSO-d6)δ5.04(s,1H),4.85(s,1H),4.37(s,1H),3.54(s,2H),2.57(s,2H),2.47(dd,J＝44.3,41.4Hz,6H),2.29(s,1H),2.22(s,1H),2.19(s,1H),1.82(s,1H),1.65(s,2H),1.58(d,J＝8.0Hz,2H),1.53–1.46(m,6H),1.39(t,J＝7.8Hz,5H),1.30(dd,J＝21.8,9.9Hz,4H),1.16(d,J＝0.4Hz,2H),1.06(s,6H),0.91(s,1H),0.88(s,12H),0.85–0.57(m,4H).
13C?NMR(125MHz,DMSO-d6)δ216.69(s),154.70(s),105.53(s),74.75(s),67.02(s),59.85(s),55.00(d,J＝14.4Hz),52.87(s),51.30(s),48.09(s),44.44(s),42.38(s),41.98(s),40.93(s),40.25(s),39.07(s),38.99(s),37.34(s),36.48(s),33.66(s),33.05(s),30.10(s),27.52(s),26.16(s),24.80(s),24.59(s),24.06(s),23.65(s),21.05(s),18.56(s),18.21(s),17.28(s).
HRMS(ESI):m/z[M+H]
+calcd?for?C
37H
62NO
2:552.4781；found:552.4787。
The low property of O-(piperidyl) the ethyl derivative anti-erythrocyte anemia experiment of embodiment 4 Cleistanone
Test the therapeutical effect of O-(piperidyl) ethyl derivative to the mice that loses blood of 1 Cleistanone
30 of ICR mices, ♀ ♂ half and half, is divided into 3 groups (n=10).Except normal saline group, every mice of other group is from eye socket venesection 0.5ml, after 24h, get again blood survey and all respectively organize index, then continuous blood-letting every day 0.5ml after gastric infusion (0.1mL/10g body weight) 1 week and administration, after last administration 1h, from eye socket venous plexus, get blood and carry out red blood cell count(RBC) (10 with the full whole bliid platelet analyzer of F-800
12/ L).
The O-of table 1 Cleistanone (piperidyl) ethyl derivative is to because of oligocythemic therapeutical effect due to losing blood
With model group comparison: * p<0.05
Result shows, O-(piperidyl) the ethyl derivative treatment of blood-letting mice through taking Cleistanone is after 7 days, and with model group comparison, its erythrocyte is significantly higher than model group, approaches normal saline group.
Two, the O-of Cleistanone (piperidyl) ethyl derivative causes oligocythemic therapeutical effect to cyclophosphamide
30 of the preventive and therapeutic effect ICR mices that mouse bone marrow cells hemopoietic function is damaged, ♀ ♂ dual-purpose, is divided into 3 groups (n=10), i.e. O-(piperidyl) the ethyl derivative 1.2mg/kg group of normal saline group, modeling group, Cleistanone, oral administration, every day 1 time.0th, except normal saline group, other respectively organized mice lumbar injection cycli phosphate amine 80mg/kg respectively, then continued administration 3 days on 5th, 10.1h after last administration, gets blood from eye socket venous plexus, surveys RBC number (10
12/ L).
The O-of table 2 Cleistanone (piperidyl) ethyl derivative is on the erythrocytic impact of caused by cyclophosphamide
With model group comparison: * * p<0.01
Result shows, with the comparison of normal saline group, cycli phosphate amine can make mouse bone marrow cells damage, causes peripheral blood cells to decline, the O-of Cleistanone (piperidyl) ethyl derivative group and model group comparison, can obviously resist cycli phosphate amine induced mice red blood cell decreased.
Three, the O-of Cleistanone (piperidyl) ethyl derivative is to oligocythemic therapeutical effect due to benzene
Impact on Induced Aplastic Anemia Mice: 30 of Kunming mouses, ♀ ♂ dual-purpose, is divided into 3 groups (n=10), except normal saline group, other group mouse subcutaneous injection benzene 0.5ml/kg, continuous 12 days, the same day of modeling, while oral administration, every day 1 time, totally 18 days, 1h after last administration, eye socket venous plexus is got blood, surveys erythrocyte.
The O-of table 3 Cleistanone (piperidyl) ethyl derivative is to oligocythemic therapeutical effect due to benzene
With model group comparison: * * p<0.01
Result shows, administration group and model group comparison can obviously resist the erythrocytic decline of Induced Aplastic Anemia Mice due to benzene.
The O-of conclusion: Cleistanone (piperidyl) the ethyl derivative erythrocyte that can significantly raise, can be used for the medicine of preparation treatment anemia.
The preparation of embodiment 5 Compound I I involved in the present invention and III tablet
Get a kind of in the middle of O-(piperidyl) ethyl derivative of 20 grams of Cleistanone 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 I I involved in the present invention and III capsule
Get a kind of in the middle of O-(piperidyl) ethyl derivative of 20 grams of Cleistanone or its pharmaceutically acceptable salt, add the conventional adjuvant of preparing capsule as 180 grams of starch, mix, encapsulatedly make 1000.
Claims (5)
1. O-(piperidyl) ethyl derivative (III) and the application of pharmaceutically acceptable salt in the low property for the treatment of erythrocyte anemia medicine thereof with the Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone of structure shown in formula III:
2. a kind of O-(piperidyl) ethyl derivative (III) and the application of pharmaceutically acceptable salt in the low property for the treatment of erythrocyte anemia medicine thereof with the Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone of structure shown in formula III as claimed in claim 1, is characterized by: the low property of described erythrocyte anemia is caused by losing blood.
3. a kind of O-(piperidyl) ethyl derivative (III) and the application of pharmaceutically acceptable salt in the low property for the treatment of erythrocyte anemia medicine thereof with the Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone of structure shown in formula III as claimed in claim 1, is characterized by: the low property of described erythrocyte anemia is low by the caused erythrocyte of chemical substance.
4. a kind of O-(piperidyl) ethyl derivative (III) and the application of pharmaceutically acceptable salt in the low property for the treatment of erythrocyte anemia medicine thereof with the Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone of structure shown in formula III as claimed in claim 3, it is characterized by: described chemical substance is benzene, the low property of described erythrocyte anemia is by the aplastic anemia due to benzene.
5. a kind of O-(piperidyl) ethyl derivative (III) and the application of pharmaceutically acceptable salt in the low property for the treatment of erythrocyte anemia medicine thereof with the Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone of structure shown in formula III as claimed in claim 3, it is characterized by: described chemical substance is cycli phosphate amine, the low property of described erythrocyte anemia is by red blood cell decreased due to cycli phosphate amine.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104758295A (en) * | 2015-03-10 | 2015-07-08 | 南京大学 | Application of O-(triazolyl)ethyl derivative of cleistanone in preparation of anti-low-erythrocyte anemia drug |
| CN104800222A (en) * | 2015-04-29 | 2015-07-29 | 南京大学 | Application of O-(benzimidazolyl) ethyl derivative of cleistanone in preparing drug for preventing red blood cell hypoplastic anemia |
| CN104922123A (en) * | 2015-05-27 | 2015-09-23 | 南京大学 | Application of O-(diethylin) ethyl derivative of Daphmalenine A to preparation of drug for resisting red blood cell hypoplastic anemia |
| CN105250258A (en) * | 2015-11-09 | 2016-01-20 | 南京广康协生物医药技术有限公司 | Composition and application of composition in medicine for resistance of erythrocyte low anemia |
| CN105343083A (en) * | 2015-12-07 | 2016-02-24 | 南京海澳斯生物医药科技有限公司 | Composition and application of composition in medicines for resisting low erythrocyte anemia |
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| CN105616403A (en) * | 2015-07-16 | 2016-06-01 | 南京海澳斯生物医药科技有限公司 | Composition and application thereof to low red blood cell anemia resisting medicine |
| CN106074528A (en) * | 2016-05-24 | 2016-11-09 | 南京海澳斯生物医药科技有限公司 | The composition of Ah draw'sing Bick acid triazolyl and 1H tetrazole radical derivative is for preparing anti-erythrocyte low property anaemia medicine |
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| CN104800222A (en) * | 2015-04-29 | 2015-07-29 | 南京大学 | Application of O-(benzimidazolyl) ethyl derivative of cleistanone in preparing drug for preventing red blood cell hypoplastic anemia |
| CN104922123A (en) * | 2015-05-27 | 2015-09-23 | 南京大学 | Application of O-(diethylin) ethyl derivative of Daphmalenine A to preparation of drug for resisting red blood cell hypoplastic anemia |
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| CN105250258A (en) * | 2015-11-09 | 2016-01-20 | 南京广康协生物医药技术有限公司 | Composition and application of composition in medicine for resistance of erythrocyte low anemia |
| CN105343083A (en) * | 2015-12-07 | 2016-02-24 | 南京海澳斯生物医药科技有限公司 | Composition and application of composition in medicines for resisting low erythrocyte anemia |
| CN106074528A (en) * | 2016-05-24 | 2016-11-09 | 南京海澳斯生物医药科技有限公司 | The composition of Ah draw'sing Bick acid triazolyl and 1H tetrazole radical derivative is for preparing anti-erythrocyte low property anaemia medicine |
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