CN107266431A - Herba Peperomiae pellucidae element E or derivatives thereof and application thereof - Google Patents
Herba Peperomiae pellucidae element E or derivatives thereof and application thereof Download PDFInfo
- Publication number
- CN107266431A CN107266431A CN201710571549.XA CN201710571549A CN107266431A CN 107266431 A CN107266431 A CN 107266431A CN 201710571549 A CN201710571549 A CN 201710571549A CN 107266431 A CN107266431 A CN 107266431A
- Authority
- CN
- China
- Prior art keywords
- derivatives
- herba peperomiae
- peperomiae pellucidae
- och
- pellucidae
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 0 *[C@](CO1)C(C2)*1=***2IN Chemical compound *[C@](CO1)C(C2)*1=***2IN 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention discloses a kind of Herba Peperomiae pellucidae element E or derivatives thereof and application thereof.Structural formula is Wherein, R1=R2For double bond or R2For H, R1For C1Substituted hydrocarbon radical, R5For hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aryl alkyl, aryl alkenyl or heterocyclic radical.The preparation method of Herba Peperomiae pellucidae element E derivatives is to be heated at 70 80 DEG C by Herba Peperomiae pellucidae element E, methanol and triethylamine hybrid reaction or by Herba Peperomiae pellucidae element A, methanol, triethylamine reacting to obtain intermediate product, then is reacted with the reaction of phenylseleno chlorine, trimethyl silicon substrate trifluoromethanesulfonic acid, dichloromethane at 0 DEG C.Herba Peperomiae pellucidae element E of the present invention or derivatives thereof can be used for the medicine for preparing prevention or treating cancer, be especially suitable for treatment acute myeloid leukaemia.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, and in particular to Herba Peperomiae pellucidae element E or derivatives thereof and application thereof.
Background technology
Acute myeloid leukaemia (Acute Myeloid Leukemia, abbreviation AML) is current teenager and less than 35 years old
Crowd's incidence of disease highest malignant tumour, in recent years its incidence of disease have rise year by year trend (N.Engl.J.Med.2015,
373,1136-52；Nat.Immun.2004,5,738-43).With the continuous improvement of therapeutic scheme, AML remission rate rises year by year
Height, but recurrence occurs in most of patient, once recurrence, poor prognosis (N.Engl.J.Med.2006,355,1253-60；
Acta.Pharmacol.Sin.2013,34,732-40).Leukemic stem cells (Leukemia Stem Cells, abbreviation LSC)
The cells of origin of myelogenous leukemia, this small set of cell can self-renewing with differentiation, maintain the development of leukaemia, due to
It is mostly in resting stage (G0/1Phase) and abnormal expression signal path, this cause they often escape from present it is clinically main
For the chemotherapeutics of fast proliferating cells, basic reason as AML recurrent intractables (Nat.Biotechnol.2007,25,
1315-21).Current clinical anti-AML chemotherapeutics mainly includes：Antimetabolic nucleoside medicine (Cytarabine,
Fludarabine)；DNA methylation class medicine (Decitabine, Azacitidine) and anthracene nucleus medicament
(Idarubicin).Although to AML mitigations substantially, shortcoming is very prominent, is mainly reflected in for these medicines：(1) it is easily multiple
Hair：It is in G0/1The LSC of resting stage is insensitive to said medicine, and there is multidrug resistance, resists the phenomenon of apoptotic signal, causes
Tumour easily occurs again after alleviation；(2) poor selectivity：The anti-AML of said medicine also has stronger simultaneously, to normal marrow cell
Inhibitory action, causes the bone marrow suppression of dose dependent, therefore easy bleeding, infection over the course for the treatment of, and this is also AML chemotherapy
There is dead most important reason (Leukemia.2001,15,875-90).Therefore, AML is fundamentally treated, prevents multiple
Hair, finds and is directed to LSC and the drug molecule harmless to normal haematopoetic has great critical significance.
Herba Peperomiae pellucidae element E (abbreviation PepE) is found in Piperaceae (Piperaceae) Herba Peperomiae pellucidae category (Peperomia) people first
Between plants for anticancer dindygulen peperomia herb (Peperomia dindygulensis Miq.) herb in (Phytochemistry.1998,
49,2129-3131).J.L.Wu seminars have reported for work PepE anti tumor activity in vitro first, find it to adenocarcinoma of lung, uterine neck
Cancer, the in-vitro multiplication inhibitory activity of liver cancer (J.Nat.Prod., 2005,68,1656-1660).Patent applicant seminar enters one
Step expands the screening scope of tumor cell in vitro, and the activity in vivo evaluation to the compound first, find PepE to stomach cancer,
Cancer of the esophagus, non-small cell lung cancer and breast cancer also have good inhibitory activity, wherein to stomach cancer (SGC-7901), non-small cell
The susceptibility highest of lung cancer (A549) cell line (suppresses IC50Value is respectively 1.90 and 3.99 μM), the toxicity to normal cell is remote
Less than tumour cell；Active animal evaluation shows that (i.g.15mg/kg/d 21 days) PepE can preferably press down under effective dose
The growth of stomach cancer processed, non-small cell lung cancer solid tumor in nude mouse, internal antitumor activity is notable, with positive drug group (such as
Taxol etc.) compare, the compound molecule without obvious bone marrow inhibition and liver, renal toxicity (Cancer Sci.2016,
10,1506-1519；Phytomedicine.,2016,3,818-827).
The content of the invention
In view of the shortcomings of the prior art, should it is an object of the invention to provide Herba Peperomiae pellucidae element E or derivatives thereof and application thereof
Medicine is especially suitable for treating acute myeloid leukaemia.
Herba Peperomiae pellucidae element E or derivatives thereof, structural formula is
Wherein, R1≠R2, R2For H, R1For C1
Substituted hydrocarbon radical, R5For hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aryl alkyl, aryl alkenyl or heterocyclic radical.
It is as improved, the C1Substituted hydrocarbon radical is fatty amine, ring grease amine, fragrant fat amine, amino acid or fragrant heterolipid amine.
It is above-mentionedPreparation method be
, wherein, R2For H, R1ForR3,R4For alkyl, cycloalkyl, alkylaryl or alkyl aromatic heterocyclic.
It is as improved, it is describedFor
It is any.
It is above-mentionedPreparation method be：
It is describedFor
Applications of the above-mentioned Herba Peperomiae pellucidae element E or derivatives thereof on the medicine for preparing prevention or treating cancer.
It is that the cancer is acute myeloid leukaemia as improved.
A kind of pharmaceutical composition, including Herba Peperomiae pellucidae element E described in claim 1 or derivatives thereof and pharmaceutically acceptable
Carrier.
It is that described Herba Peperomiae pellucidae element E or derivatives thereof mass fraction is 0.1-99% as improved.
It is that described Herba Peperomiae pellucidae element E or derivatives thereof mass fraction is 0.5-90% as improved.
Beneficial effect：
The present invention has found that Herba Peperomiae pellucidae element E or derivatives thereof has and treats acute myelogenous white blood on the basis of early-stage Study
The purposes of disease.Herba Peperomiae pellucidae element E and its derivative are not only very sensitive to many plants of AML cell lines, are in while can significantly inhibit
The growth of the leukemic stem cells (LSC) of resting stage, the damage to people's normal haematopoetic (HSC) will be significantly lower than LSC, carry
Show that it has the potentiality for the drug molecule for developing into novel targeted anti-LSC, can fundamentally treat AML, compared to clinical existing use
Anti- AML medicines it is with the obvious advantage.The Herba Peperomiae pellucidae element E and its derivative of the present invention is to acute myeloid leukemia cells in children and leukaemia
Stem cell shows stronger inhibitory activity, does not show obvious killing to normal bone marrow cell and candidate stem cell and makees
With.
When the compounds of this invention is used as medicine, can directly it use, or used in the form of pharmaceutical composition.The medicine
Composition contains 0.1~99%, preferably 0.5~90% the compounds of this invention, and remaining is pharmaceutically acceptable, to people
The nontoxic and inert pharmaceutical acceptable carrier of animal and/or excipient or with other anti-cancer agent in combination medications.The combination of the present invention
Thing can be prepared into parenteral solution, tablet and capsule etc., and use more facilitates.
Embodiment
The compound II of embodiment 1 preparation
Preparation method：Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to
In 100mL reaction bulbs, 1.0mmol dimethylamine is slowly added into, normal-temperature reaction 18h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Second
Acetoacetic ester=1:1) pale yellow oil 198.2mg, yield 86%, are obtained.The compound II prepared structured data：
Molecular formula：C24H26NO8；
Molecular weight：m/z 458.1798[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.566,6.514 (d, H-6 ', 6 ", J=1.9Hz 2H), 6.471,6.432 (d,
H-2 ', 2 ", J=1.9Hz, 2H), 5.946 (m ,-OCH2O-, 4H), 4.362 (dd, H-4a, J=8.95,12.1Hz, 1H),
4.132 (d, H-5, J=8.95Hz, 1H), 4.01 (dd, H-4b, J=4.95,12.1Hz, 1H), 3.925 (s ,-OCH3,3H),
3.913(3H,s,-OCH3), 3.402 (m, H-3,1H), 2.526 (dd, H-6a, J=9.5,14.5Hz, 1H), 2.438 (dd, H-
6b, J=6.0,15.0Hz, 1H), 2.195 (dd, H-2, J=6.2,14.5Hz, 1H), 2.102 (s, 6H, 7,8-CH3).13C-
NMRδC178.7(C-1)；134.2,134.1(C-1’,1”)；149.5,149.2(C-3’,3”)；143.6,143.5(C-5’,
5”)；136.6,136.9(C-4’,4”)；108.1,107.9(C-6’,6”)；101.9,101.3(C-2’,2”)；101.5,
101.6(-OCH2O-)；41.4(C-3)；55.4(C-5)；56.8,57.0(-OCH3)；70.6(C-4)；44.7(C-2)；60.4
(C-6)；45.8(C-7,C-8).
The compound III of embodiment 2 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol diethylamine is slowly added into, normal-temperature reaction 18h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Ethyl acetate=
1.5:1) pale yellow oil 187.1mg, yield 77.1%, are obtained.The compound III prepared structured data：
Molecular formula：C26H31NO8；
Molecular weight：m/z 486.2111[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.543,6.477 (d, H-6 ', 6 ", J=1.9Hz, 2H), 6.417 (d, H-2 ',
2 ", J=1.9Hz, 2H), 5.942 (m ,-OCH2O-, 4H), 4.382 (m, H-4,2H), 4.05 (d, H-5, J=5Hz, 1H),
3.923(s,-OCH3,3H),3.905(3H,s,-OCH3), 3.288 (m, H-3,1H), 2.692 (dd, H-6a, J=10.0,
15.5Hz, 1H), 2.481 (m, H-6b, H-7, H-8,5H), 2.383 (m, H-2,1H), 0.982 (t, 6H, J=8.0Hz, 7,8-
CH3).13C-NMRδC179.0(C-1)；134.2,134.1(C-1’,1”)；149.4,149.2(C-3’,3”)；143.6,
143.5(C-5’,5”)；137.1,136.6(C-4’,4”)；108.4,108.3(C-6’,6”)；101.7,101.6(C-2’,
2”)；101.5,101.4(-OCH2O-)；42.2(C-3)；52.7(C-5)；57.0,56.8(-OCH3)；70.6(C-4)；44.8
(C-2)；56.9(C-6)；54.7(C-7,C-8)；11.2(C-9,C-10).
The compound IV of embodiment 3 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol N- methyl ethyl-amines are slowly added into, normal-temperature reaction 18h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Acetic acid second
Ester=1.5:1) pale yellow oil 183.2mg, yield 77.5%, are obtained.The compound IV prepared structured data：
Molecular formula：C25H29NO8；
Molecular weight：m/z 472.1947[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.543,6.477 (d, H-6 ', 6 ", J=1.9Hz, 2H), 6.417 (d, H-2 ',
2 ", J=1.9Hz, 2H), 5.942 (m ,-OCH2O-, 4H), 4.382 (m, H-4,2H), 4.05 (d, H-5, J=5Hz, 1H),
3.923(s,-OCH3,3H),3.905(3H,s,-OCH3), 3.288 (m, H-3,1H), 2.692 (dd, H-6a, J=10.0,
15.5Hz, 1H), 2.481 (m, H-6b, H-7, H-8,5H), 2.383 (m, H-2,1H), 0.982 (t, 6H, J=8.0Hz, 7,8-
CH3).13C-NMRδC179.0(C-1)；134.2,134.1(C-1’,1”)；149.4,149.2(C-3’,3”)；143.6,
143.5(C-5’,5”)；137.1,136.6(C-4’,4”)；108.4,108.3(C-6’,6”)；101.7,101.6(C-2’,
2”)；101.5,101.4(-OCH2O-)；42.2(C-3)；52.7(C-5)；57.0,56.8(-OCH3)；70.6(C-4)；44.8
(C-2)；56.9(C-6)；54.7(C-7,C-8)；
11.2(C-9,C-10)。
The compound V of embodiment 4 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol N methyl pmpyl amine is slowly added into, normal-temperature reaction 18h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Acetic acid second
Ester=2:1) pale yellow oil 201.9mg, yield 83.1%, are obtained.The compound V prepared structured data：
Molecular formula：C26H31NO8；
Molecular weight：m/z 486.2104[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.558,6.484 (d, H-6 ', 6 ", J=1.8Hz, 2H), 6.437,6.420 (d,
H-2 ', 2 ", J=1.8Hz, 2H), 5.946 (m ,-OCH2O-, 4H), 4.358 (dd, H-4a, J=9.0,12.1Hz 1H),
4.041 (d, H-5, J=4.5Hz, 1H), 4.023 (dd, H-4b, J=4.5,12.1Hz, 1H) 3.920 (s ,-OCH3,3H),
3.907(3H,s,-OCH3), 3.363 (m, H-3,1H), 2.624 (dd, H-6a, J=5.75,15.9Hz, 1H), 2.476 (m, H-
2,1H), 2.288 (dd, H-6b, J=6.3,15.9Hz, 1H), 2.238 (t, H-8, J=9.3Hz, 2H), 2.033 (s, 3H, H-
7),1.463(m,2H,H-9),0.914(s,3H,H-10).13C-NMRδC178.9(C-1)；149.5,149.2(C-3’,3”)；
143.6,143.5(C-5’,5”)；137.1,136.6(C-4’,4”)；134.2,134.1(C-1’,1”)；108.3,108.2(C-
6’,6”)；101.8,101.5(C-2’,2”)；101.4,101.3(-OCH2O-)；70.6(C-4)；60.3(C-8)；56.9,
56.8(-OCH3)；56.7(C-6)；55.1(C-5)；44.7(C-2)；41.8,41.7(C-7,C-3)；20.3(C-9)；11.8
(C-10)。
The compound VI of embodiment 5 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol 2- (methylamino) ethanol is slowly added into, normal-temperature reaction 24h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Second
Acetoacetic ester=1.5:1) pale yellow oil 178.1mg, yield 72.9%, are obtained.The compound VI prepared structured data：
Molecular formula：C25H29NO9；
Molecular weight：m/z 488.1889[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.504,6.500 (d, H-6 ', 6 ", J=1.9Hz, 2H), 6.477,6.473 (d,
H-2 ', 2 ", J=1.9Hz, 2H), 5.954 (m ,-OCH2O-, 4H), 4.358 (dd, H-4a, J=9.2,12.2Hz 1H),
4.048 (d, H-5, J=3.0Hz, 1H), 3.996 (dd, H-4b, J=5.3,12.3Hz, 1H) 3.919 (s ,-OCH3,6H),
3.606(m,H-9,2H),3.175(m,H-3,1H),2.499(m,H-6,H-8,H-2,5H),2.076(s,H-7,3H),2.238
(t, H-8, J=9.3Hz, 2H), 2.033 (s, 3H, H-7)13C-NMRδC178.5(C-1)；149.5,149.3(C-3’,3”)；
143.7,143.6(C-5’,5”)；136.6,136.4(C-4’,4”)；134.3,134.2(C-1’,1”)；108.2,108.1(C-
6’,6”)；101.6,101.5(C-2’,2”)；101.2(-OCH2O-)；70.5(C-4)；59.5(C-8)；58.9(C-9)；57.4
(C-6)；56.9(-OCH3)；55.3(C-5)；44.3(C-2)；42.4(C-7)；41.7(C-3).
The compound VII of embodiment 6 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (5.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol creatine is slowly added into, 80 DEG C of heating reflux reaction 24h are concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Acetone
=2:1) pale yellow oil 155.7mg, yield 62.2%, are obtained.The compound VII prepared structured data：
Molecular formula：C25H27NO10；
Molecular weight：m/z 523.1538[M+Na]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.503,6.475 (d, H-6 ', 6 ", J=1.9Hz, 2H), 6.477,6.473 (d,
H-2 ', 2 ", J=1.9Hz, 2H), 5.954 (m ,-OCH2O-, 4H), 4.372 (dd, H-4a, J=9.2,12.3Hz 1H),
4.045 (d, H-5, J=2.9Hz, 1H), 4.003 (dd, H-4b, J=5.3,12.3Hz, 1H), 3.920 (s ,-OCH3,6H),
3.616(m,H-8,2H),3.175(m,H-3,1H),2.547(m,H-6,2H),2.415(m,H-2,1H),2.076(s,H-7,
3H).13C-NMRδC178.4(C-1)；176.5(C-9)；149.5,149.3(C-3’,3”)；143.7,143.6(C-5’,5”)；
136.6,136.4(C-4’,4”)；134.3(C-1’,1”)；108.2,108.1(C-6’,6”)；101.6,101.2(C-2’,
2”)；101.5(-OCH2O-)；70.5(C-4)；60.4(C-8)；58.4(C-6)；57.0(-OCH3)；55.4(C-5)；44.4(C-
2)；42.8(C-7)；40.7(C-3).
The compound VIII of embodiment 7 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol pyrroles is slowly added into, normal-temperature reaction 18h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Ethyl acetate=2:
1) pale yellow oil 211.7mg, yield 87.4%, are obtained.The compound VIII prepared structured data：
Molecular formula：C26H29NO8；
Molecular weight：m/z 484.1951[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.595,6.573 (d, H-6 ', 6 ", J=1.9Hz, 2H), 6.542,6.454 (d,
H-2 ', 2 ", J=1.9Hz, 2H), 5.909 (m ,-OCH2O-,4H),4.012,3.916(m,H-4,2H),3.901(s,-OCH3,
3H),3.888(s,-OCH3, 3H), 3.821 (d, H-5, J=4.7Hz, 1H), 2.471 (m, H-2,1H)；3.337(m,H-3,
1H),2.589,2.273(m,H-6,2H),2.236(m,H-7,10,4H).13C-NMRδC173.1(C-1)；149.2,148.9
(C-3’,3”)；143.6,143.3(C-5’,5”)；138.4,138.2(C-4’,4”)；133.7,133.6(C-1’,1”)；
108.3,107.7(C-6’,6”)；101.7,101.4(C-2’,2”)；101.2,101.1(-OCH2O-)；71.2(C-4)；58.2
(C-7,C10)；57.0(C-6)；56.7(-OCH3)；54.3(C-5)；44.3(C-2)；43.7(C-3),23.6(C-8,9).
The compound IX of embodiment 8 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol morpholine is slowly added into, normal-temperature reaction 24h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Ethyl acetate=
2:1) pale yellow oil 207.7mg, yield 83.1%, are obtained.The compound IX prepared structured data：
Molecular formula：C26H29NO9；
Molecular weight：m/z 500.1893[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.564,6.503 (d, H-6 ', 6 ", J=1.9Hz, 2H), 6.413 (d, H-2 ',
2 ", J=1.9Hz, 2H), 5.951 (m ,-OCH2O-, 4H), 4.342 (dd, H-4a, J=9.2,12.2Hz1H), 4.308 (d, H-
5, J=4.2Hz, 1H), 4.019 (dd, H-4b, J=5.3,12.3Hz, 1H), 3.931 (s ,-OCH3,3H),3.909(s,-
OCH3,3H),3.678(m,H-8,9,4H),3.337(m,H-3,1H),2.589,2.273(m,H-6,2H),2.236(m,H-7,
10,4H).13C-NMRδC178.5(C-1)；149.5,149.2(C-3’,3”)；143.6,143.4(C-5’,5”)；136.8,
136.6(C-4’,4”)；134.2,134.1(C-1’,1”)；108.7,108.3(C-6’,6”)；101.5,101.4(C-2’,
2”)；101.4,101.1(-OCH2O-)；70.6(C-4)；67.0,66.8(C-8,9)；57.2(-OCH3)；56.9(C-6)；55.0
(C-5)；52.0(C-7,10)；43.9(C-2)；41.8(C-3).
The compound X of embodiment 9 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol 4- methyl piperidines are slowly added into, normal-temperature reaction 24h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Acetic acid second
Ester=2:1) pale yellow oil 201.3mg, yield 78.6%, are obtained.The compound IX prepared structured data：
Molecular formula：C28H33NO8；
Molecular weight：m/z 512.2271[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.564,6.507 (d, H-6 ', 6 ", J=1.8Hz, 2H), 6.417,6.408 (d,
H-2 ', 2 ", J=1.8Hz, 2H), 5.936 (m ,-OCH2O-, 4H), 4.355 (dd, H-4a, J=8.7,12.1Hz 1H),
4.140 (d, H-5, J=4.7Hz, 1H), 4.017 (dd, H-4b, J=4.5,12.1Hz, 1H) 3.905 (s ,-OCH3,3H),
3.887(s,-OCH3, 3H), 3.361 (m, H-3,1H), 2.733 (m, H-7a, 1H), 2.569 (dd, H-6b, J=15.6,
10.0Hz, 1H), 2.479 (m, H-2,1H), 2.320 (m, H-11a, 1H), 2.243 (dd, H-6a, J=15.6,5.8Hz, 1H),
2.011(m,H-11b,1H),1.813(m,H-7b,1H),1.617(m,H-8a,10a,2H),1.504(m,H-9,1H),1.248
(m, H-8b, 9b, 2H), 0.934 (d, H-12, J=7.8Hz, 3H)13C-NMRδC178.9(C-1)；149.5,149.2(C-
3’,3”)；143.6,143.4(C-5’,5”)；137.0,136.7(C-4’,4”)；134.2,134.1(C-1’,1”)；108.5,
108.3(C-6’,6”)；101.5(C-2’,2”)；101.4,101.2(-OCH2O-)；70.7(C-4)；57.1(-OCH3)；56.8
(C-6)；55.1(C-5)；54.2,53.2(C-7,11)；44.4(C-2)；41.7(C-3)；28.9,28.5(C-8,10)；21.0
(C-9)；14.2(C-12).
The compound XI of embodiment 10 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (4.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol 4- piperidine carbinols are slowly added into, normal-temperature reaction 24h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Acetic acid second
Ester=1.5:1) pale yellow oil 219.3mg, yield 82.9%, are obtained.The compound IX prepared structured data：
Molecular formula：C28H33NO9；
Molecular weight：m/z 528.2218[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.564,6.500 (d, H-6 ', 6 ", J=1.8Hz, 2H), 6.410 (d, H-2 ',
2 ", J=1.8Hz, 2H), 5.945 (m ,-OCH2O-, 4H), 4.355 (dd, H-4a, J=8.8,12.2Hz1H), 4.140 (d, H-
5, J=8.9Hz, 1H), 4.022 (dd, H-4b, J=4.5,12.1Hz, 1H), 3.926 (s ,-OCH3,3H),3.903(s,-
OCH3, 3H), 3.517 (d, H-12, J=7.8Hz, 2H), 3.360 (m, H-3,1H), 2.733 (m, H-7a, 1H), 2.587 (dd,
H-6b, J=15.7,10.1Hz, 1H), 2.479 (m, H-2,1H), 2.391 (m, H-11a, 1H), 2.263 (dd, H-6a, J=
15.7,6.0Hz,1H),2.045(m,H-11b,1H),1.851(m,H-7b,1H),1.736(m,H-8a,10a,2H),1.470
(m,H-9,1H),1.296(m,H-8b,10b,2H).13C-NMRδC178.9(C-1)；149.5,149.2(C-3’,3”)；
143.6,143.4(C-5’,5”)；137.0,136.7(C-4’,4”)；134.2,134.1(C-1’,1”)；108.5,108.3(C-
6’,6”)；101.5(C-2’,2”)；101.4,101.2(-OCH2O-)；70.7(C-4)；67.8(C-12)；57.1(C-6)；
57.0,56.9(-OCH3)；55.1(C-5)；54.5,53.2(C-7,C-11),44.4(C-2)；41.7(C-3)；38.3(C-9)；
29.0,28.5(C-8,C-10)。
The compound XII of embodiment 11 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (5.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol phenyl ethylamine is slowly added into, normal-temperature reaction 24h is concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Ethyl acetate=
3:1) pale yellow oil 177.5mg, yield 68.3%, are obtained.The compound IX prepared structured data：
Molecular formula：C29H29NO8；
Molecular weight：m/z 520.1952[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH7.312 (m, H-2 " '~6 " ', 5H), and 6.468,6.435 (d, H-6 ', 6 ", J=
2.0Hz, 2H), and 6.399,6.309 (d, H-2 ', 2 ", J=2.0Hz, 2H), 5.914 (m ,-OCH2O-,4H),4.351(m,H-
4a, 1H), 4.142 (dd, H-4b, J=8.9,17.2Hz, 1H), 3.906,3.899 (s ,-OCH3,6H),3.626(m,H-7,
2H), 3.552 (d, H-5, J=15.1Hz, 1H), 3.380 (m, H-3,1H), 2.673 (dd, H-6a, J=5.5,15.2Hz,
1H),2.529(m,H-6b,1H),2.293(m,H-2,1H).13C-NMRδC175.5(C-1)；149.3,149.0(C-3’,
3”)；143.6,143.5(C-5’,5”)；139.5(C-1”’)；138.9,138.3(C-1’,1”)；133.9,133.8(C-4’,
4”)；128.7,128.6(C-3”’,5”’)；128.0,127.9(C-2”’,6””)；127.1(C-4”’)；107.9,107.7(C-
6’,6”)；101.5,101.4(C-2’,2”)；101.3,101.2(-OCH2O-)；70.3(C-4)；56.9,56.8(-OCH3)；
53.9(C-7)；51.7(C-5)；45.8(C-6)；44.1(C-2)；42.2(C-3)..
The compound XIII of embodiment 12 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (5.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol 4- hydroxy-5-methyl epoxide phenyl ethylamines are slowly added into, 70 DEG C of reaction 24h are concentrated under reduced pressure, silica gel column chromatography (stone
Oily ether：Ethyl acetate=2:1) pale yellow oil 220.7mg, yield 76.1%, are obtained.The compound XIII prepared knot
Structure data：
Molecular formula：C29H29NO8；
Molecular weight：m/z 580.2146[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.873 (d, H-3 " ', J=8.5Hz, 1H), 6.706 (d, H-6 " ', J=
2.0Hz, 1H), 6.706 (d, H-6 " ', J=2.0Hz, 1H), 6.681 (dd, H-2 " ', J=2.0,8.5Hz, 1H), 6.468,
6.460 (d, H-6 ', 6 ", J=2.0Hz, 2H), 6.425,6.400 (d, H-2 ', 2 ", J=2.0Hz, 2H), 5.940 (m ,-
OCH2O-, 4H), 4.294 (m, H-4a, 1H), 4.142 (dd, H-4b, J=8.9,17.2Hz, 1H), 3.917,3.889,3.890
(s,-OCH3, 9H), 3.607 (d, H-5, J=14.5Hz, 1H), 3.269 (m, H-3,1H), 2.800 (dd, H-6a, J=10.0,
15.5Hz,1H),2.733(m,H-6b,1H),2.646(m,H-7,2H),2,496(m,H-8,2H)2.291(m,H-2,1H)
.13C-NMRδC178.6(C-1)；149.5,149.4(C-3’,3”)；146.5(C-5”’)；144.0(C-4”’),143.6,
143.7(C-5’,5”)；136.7,136.4(C-4’,4”)；134.3,134.2(C-1’,1”)；131.8(C-1”’),121.2
(C-2”’),114.4(C-3”’),111.3(C-6”’),107.9,108.1(C-6’,6”)；101.5(-OCH2O-)；101.3,
101.1(C-2’,2”)；70.9(C-4)；57.0,56.9,56.1(-OCH3)；55.8(C-5)；51.3(C-7)；48.0(C-6)；
45.9(C-2)；41.6(C-3)；35.9(C-8).
The compound XIV of embodiment 13 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (5.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, 1.0mmol 4- hydroxyphenethylamines are slowly added into, 70 DEG C of reaction 24h are concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Acetic acid
Ethyl ester=2:1) pale yellow oil 207.7mg, yield 75.2%, are obtained.The compound XIV prepared structured data：
Molecular formula：C30H31NO9；
Molecular weight：m/z 550.2053[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH7.044 (d, H-2 " ', 6 " ', J=10.6Hz, 2H), 6.780 (d, H-3 " ', 5 " '
J=10.6Hz, 2H), 6.449,6.411 (d, H-6 ', 6 ", J=2.0Hz, 2H), 6.403,6.389 (d, H-2 ', 2 ", J=
2.0Hz,2H),5.936(m,-OCH2O-, 4H), 4.302 (m, H-4a, 1H), 4.157 (dd, H-4b, J=8.9,17.2Hz,
1H),3.918,3.886(s,-OCH3, 6H), 3.585 (d, H-5, J=14.5Hz, 1H), 3.205 (m, H-3,1H), 2.764
(m,H-6,2H),2.609(m,H-7,2H),2.524(m,H-8,2H),2.262(m,H-2,1H).13C-NMRδC 178.7(C-
1)；154.2(C-4”’)；149.5,149.4(C-3’,3”)；143.5,143.6(C-5’,5”)；136.7,136.4(C-4’,
4”)；134.3,134.2(C-1’,1”)；131.9(C-1”’),129.8(C-2”’,6”’)；115.5(C-3”’,5”’)；
108.1,107.8(C-6’,6”)；101.5(-OCH2O-)；101.3,101.2(C-2’,2”)；70.9(C-4)；57.0,56.9
(-OCH3)；56.1(C-5)；51.2(C-7)；48.0(C-6)；45.9(C-2)；41.5(C-3)；35.3(C-8.
The compound XV of embodiment 14 preparation
Herba Peperomiae pellucidae element E (206mg, 0.50mmol), triethylamine (5.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, the 1.0mmol chloro- pyridines of 5- aminomethyls -2- are slowly added into, 70 DEG C of reaction 24h are concentrated under reduced pressure, silica gel column chromatography (oil
Ether：Ethyl acetate=1.5:1) pale yellow oil 187.3mg, yield 67.6%, are obtained.The compound XIV prepared knot
Structure data：
Molecular formula：C28H27ClN2O8；
Molecular weight：m/z 555.1605[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH8.262 (d, H-2 " ', J=2.7Hz, 1H), 7.586 (dd, H-5 " ', J=2.7,
10.2Hz, 1H), 7.313 (d, H-4 " ', J=10.2Hz, 1H), 6.478,6.417 (d, H-2 ', 2 ", J=1.8Hz, 2H),
5.943(m,-OCH2O-, 4H), 4.339 (dd, H-4a, J=10,12Hz 1H), 4.140 (dd, H-4b, J=10.0,
15.0Hz,1H),3.922(s,-OCH3,3H),3.889(3H,s,-OCH3), 3.630 (d, H-7, J=15.0Hz, 2H), 3.246
(m, H-3,1H), 2.673 (dd, H-6a, J=5.5,15.2Hz, 1H), 2.529 (m, H-6b, 1H), 2.293 (m, H-2,1H)
.13C-NMRδC178.4(C-1)；150.2(C-2”’)；149.5,149.4(C-3’,3”)；149.2(C-3”’)；143.7,
143.5(C-5’,5”)；138.5(C-5”’)；136.6,136.0(C-4’,4”)；134.4,134.3(C-1’,1”)；134.2
(C-1”’)；124.1(C-4”’)；108.0,107.9(C-6’,6”)；101.6,101.5(C-2’,2”)；101.1(-
OCH2O-)；70.9(C-4)；57.0(-OCH3)；56.2(C-7)；51.2(C-5)；45.8(C-2)；42.0(C-3).
The compound XVI of embodiment 15 preparation
Herba Peperomiae pellucidae element A (414mg, 0.10mmol), triethylamine (5.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, the methanol solution of 2.0mmol amine is slowly added into, 80 DEG C of reaction 24h are concentrated under reduced pressure, silica gel column chromatography (petroleum ether：Acetic acid
Ethyl ester=4:1) yellow oil 259.7mg compound XX yields 62.7%, are obtained.
Compound XX (206mg, 0.5mmol) is dissolved in triethylamine, after 0 DEG C of stirring 10min, fluoroform sulphur is slowly added to
After sour front three estersil (6.0mmol), 0 DEG C of stirring 40min, phenylseleno chlorine (1.0mmol) is added, 0 DEG C of reaction 30min is depressurized dense
Contracting, silica gel column chromatography (petroleum ether：Ethyl acetate=4:1) yellow oil 196.5mg compound XXI, yield 70.6%, are obtained.
Compound XXI (139mg, 0.25mmol) is dissolved in tetrahydrofuran (5mL), glacial acetic acid is slowly added into
The hydrogenperoxide steam generator (0.75mmol) that 30% is slowly added into after (0.75mmol), 0 DEG C of stirring 10min continues 0 DEG C of stirring reaction
40min.Added in reaction solution after saturated nacl aqueous solution (20mL), ethyl acetate extraction (3x10mL), combining extraction liquid, with full
Rear recycling design, silica gel column chromatography (petroleum ether-ethyl acetate=2 are washed twice with sodium bicarbonate solution (20mL):1) refine,
Obtain pale yellow oil XVI (78.3mg), yield 76.2%.
The compound XVI prepared structured data：
Molecular formula：C22H21NO7；
Molecular weight：m/z 412.1395[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.543,6.495 (d, H-6 ', 6 ", J=2.0Hz, 2H), 6.462,6.416 (d,
H-2 ', 2 ", J=2.0Hz, 2H), 6.285 (d, H-6a, J=2.3Hz, 1H), 5.998 (s, 4H ,-OCH2O-),5.140(d,H-
6b, J=2.1Hz, 1H), 4.057 (d, H-5, J=7.0Hz, 1H), 3.887 (s ,-OCH3,6H),3.651(m,H-3,1H),
3.384(m,H-4a,1H),2.863(m,H-4b,1H).13C-NMRδC160.3(C-1)；149.5,149.6(C-3’,3”)；
147.8(C-2)；143.7,143.5(C-5’,5”)；134.6,134.1(C-4,4”)；130.9,128.8(C-1’,1”)；
117.3(C-6)；108.6(C-6’,6”)；102.6,101.7(C-2’,2”)；101.5(-OCH2O-)；57.0(-OCH3)；49.5
(C-5)；43.4(C-4)；40.3(C-3).
The compound XVII of embodiment 16 preparation
Herba Peperomiae pellucidae element A (414mg, 0.10mmol), triethylamine (5.0mL), methanol (40mL) is added to 100mL reaction bulbs
In, the methanol solution of 2.0mmol methyl amine is slowly added into, 80 DEG C of reaction 24h are concentrated under reduced pressure, silica gel column chromatography (petroleum ether：
Ethyl acetate=4:1) yellow oil 271.1mg compound XXII, yield 63.1%, are obtained.
Compound XXII (214mg, 0.5mmol) is dissolved in triethylamine, after 0 DEG C of stirring 10min, fluoroform is slowly added to
After sulfonic acid front three estersil (6.0mmol), 0 DEG C of stirring 40min, phenylseleno chlorine (1.0mmol), 0 DEG C of reaction 30min, decompression are added
Concentration, silica gel column chromatography (petroleum ether：Ethyl acetate=5:1) yellow oil 211.7mg compound XXIII, yield, are obtained
74.5%.
Formula (XXIII) (142mg, 0.25mmol) is dissolved in tetrahydrofuran (5mL), glacial acetic acid is slowly added into
The hydrogenperoxide steam generator (0.75mmol) that 30% is slowly added into after (0.75mmol), 0 DEG C of stirring 10min continues 0 DEG C of stirring reaction
40min.Added in reaction solution after saturated nacl aqueous solution (20mL), ethyl acetate extraction (3x10mL), combining extraction liquid, with full
Rear recycling design, silica gel column chromatography (petroleum ether-ethyl acetate=2 are washed twice with sodium bicarbonate solution (20mL):1) refine,
Obtain pale yellow oil XVII (67.8mg), yield 63.7%.
Molecular formula：C23H23NO7；
Molecular weight：m/z 426.1355[M+H]+；
Character：Pale yellow oil；
H NMR spectroscopy diagram data：1H-NMRδH6.541,6.492 (d, H-6 ', 6 ", J=2.0Hz, 2H), 6.461,6.414 (d,
H-2 ', 2 ", J=2.0Hz, 2H), 6.280 (d, H-6a, J=2.3Hz, 1H), 5.987 (s, 4H ,-OCH2O-),5.133(d,H-
6b, J=2.1Hz, 1H), 4.032 (d, H-5, J=7.0Hz, 1H), 3.833 (s ,-OCH3,6H),3.653(m,H-3,1H),
3.370(m,H-4a,1H),3.25(s,N-CH3),2.851(m,H-4b,1H).13C-NMRδC159.3(C-1)；148.5,
147.9(C-3’,3”)；147.5(C-2)；143.2,143.0(C-5’,5”)；134.5,134.0(C-4,4”)；128.9,
128.7(C-1’,1”)；116.7(C-6)；107.5(C-6’,6”)；102.3,101.9(C-2’,2”)；101.4(-OCH2O-)；
57.7(-OCH3)；49.3(C-5)；43.2(C-4)；40.0(C-3)；35.5(N-CH3)。
The Herba Peperomiae pellucidae of embodiment 17 element E or derivatives thereof pharmacological action：
By various acute myeloid leukemia cells in children strain (including HL-60 and THP-1) and acute myeloid leukaemia stem cell
(KG-1a CD34+,CD38-) cell suspension is made into, add in Tissue Culture Plate, be separately added into Herba Peperomiae pellucidae element E or derivatives thereof
(compound II~XVII), each hole of test concentrations 5, puts 37 DEG C, 5%CO248h is cultivated under the conditions of saturated humidity, CCK-8 methods are used
Absorbance (A) value is measured in enzyme detector 570nm wavelength, the compounds of this invention is calculated to test acute myeloid leukemia cells in children
Inhibitory action, as a result as shown in table 1.
The Herba Peperomiae pellucidae of table 1 element E or derivatives thereof is to the inhibitory activity of acute myeloid leukaemia (dry) cell (IC50, μM)
Active testing result shows that the compound of screening is shown to tested acute myeloid leukemia cells in children and stem cell
Go out stronger inhibitory activity, and obvious lethal effect is not shown at 50 μM to normal marrow cell.
The preparation of the parenteral solution of embodiment 18
After compound II~XVII prepared by Herba Peperomiae pellucidae element E or embodiment is dissolved with a small amount of DMSO, routinely add injection
Parenteral solution is made in water, refined filtration, embedding, sterilizing.
The tablet of embodiment 19
Compound II~XVII prepared by Herba Peperomiae pellucidae element E or embodiment is 5 according to weight ratio with excipient:1 ratio adds
Enter excipient, pelletizing press sheet obtains tablet.
The capsule of embodiment 20
Compound II~XVII prepared by Herba Peperomiae pellucidae element E or embodiment is 5 according to weight ratio with excipient:1 ratio adds
Enter excipient, capsule is made.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
Within refreshing and principle, any modification, equivalent substitution and improvements made etc., or directly or indirectly it is used in other correlation techniques
Field, should be included in the scope of the protection.
Claims (11)
1. Herba Peperomiae pellucidae element E or derivatives thereof, it is characterised in that structural formula is Wherein, R1≠R2, and R2For H, R1For C1Substituted hydrocarbon radical, R5For hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl,
Aryl, aryl alkyl, aryl alkenyl or heterocyclic radical.
2. Herba Peperomiae pellucidae element E according to claim 1 or derivatives thereof, it is characterised in that the C1Substituted hydrocarbon radical is fat
Amine, ring grease amine, fragrant fat amine, amino acid or fragrant heterolipid amine.
3. based on Herba Peperomiae pellucidae element E described in claim 1 or derivatives thereof, it is characterised in that describedSystem
Preparation Method：
Wherein, R2For H, R1ForR3,R4For
Alkyl, cycloalkyl, alkylaryl or alkyl aromatic heterocyclic.
4. Herba Peperomiae pellucidae element E according to claim 1 or 3 or derivatives thereof, it is characterised in that describedFor
It is any.
5. Herba Peperomiae pellucidae element E according to claim 1 or derivatives thereof, it is characterised in that described
Preparation method be：
6. Herba Peperomiae pellucidae element E or derivatives thereof according to claim 1 or 5, it is characterised in that described
7. applications of the Herba Peperomiae pellucidae element E described in claim 1 or derivatives thereof on the medicine for preparing prevention or treating cancer.
8. Herba Peperomiae pellucidae element E according to claim 7 or derivatives thereof answering on the medicine for preparing prevention or treating cancer
With, it is characterised in that the cancer is acute myeloid leukaemia.
9. a kind of pharmaceutical composition, it is characterised in that including Herba Peperomiae pellucidae element E described in claim 1 or derivatives thereof and pharmacy
Upper acceptable carrier.
10. a kind of pharmaceutical composition according to claim 9, it is characterised in that described Herba Peperomiae pellucidae element E's or derivatives thereof
Mass fraction is 0.1-99%.
11. a kind of pharmaceutical composition according to claim 10, it is characterised in that described Herba Peperomiae pellucidae element E or derivatives thereof
Mass fraction be 0.5-90%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710571549.XA CN107266431A (en) | 2017-07-13 | 2017-07-13 | Herba Peperomiae pellucidae element E or derivatives thereof and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710571549.XA CN107266431A (en) | 2017-07-13 | 2017-07-13 | Herba Peperomiae pellucidae element E or derivatives thereof and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107266431A true CN107266431A (en) | 2017-10-20 |
Family
ID=60072932
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710571549.XA Withdrawn CN107266431A (en) | 2017-07-13 | 2017-07-13 | Herba Peperomiae pellucidae element E or derivatives thereof and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107266431A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965177A (en) * | 2014-05-09 | 2014-08-06 | 南京中医药大学 | Semisynthesis method of antineoplastic activity natural product peperomin E |
-
2017
- 2017-07-13 CN CN201710571549.XA patent/CN107266431A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965177A (en) * | 2014-05-09 | 2014-08-06 | 南京中医药大学 | Semisynthesis method of antineoplastic activity natural product peperomin E |
Non-Patent Citations (2)
| Title |
|---|
| MING GAO ET AL.: "Peperomin E and its synthetic amino derivatives:potent agents targeting leukaemia stem cells", 《RSC ADVANCES》 * |
| 李桂秀: "抑制血管生成类抗肿瘤一类新药PB的初步研究", 《中国优秀硕士学位论文全文数据库（电子期刊）》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103961340B (en) | A kind of LSD1 inhibitor and its application | |
| CN101289482B (en) | Cambogic acid glycoside derivates and the like, preparation and uses thereof | |
| CN101978959B (en) | Application of sphaelactone and derivative thereof to treatment of cancers | |
| CN104039796B (en) | 1-oxo/acylated Oridonin derivative acylated for-14-, and its preparation method and application | |
| CN102234259A (en) | Sphaelactone derivatives, their pharmaceutical compositions, preparation method thereof and application thereof | |
| CN105348219B (en) | Curcumin analogue and its preparation and application | |
| CN101613386B (en) | Gambogic acid cyclized analog, preparation method and application thereof | |
| JP6779318B2 (en) | Anti-metastatic 2H-selenopheno [3,2-h] chromen, their synthesis, and how to use the drug | |
| CN101213164A (en) | Aryl dihydro-naphthalene compounds, their preparation and their use as Akt inhibitor for the prevention and treatment of cancer | |
| WO2022199547A1 (en) | 7,9-dihydropurine derivative and pharmaceutical purpose thereof | |
| CN110343033A (en) | Magnolol series derivates and its preparation method and application | |
| CN104557913B (en) | Pyridopyrimidine compounds as well as preparation method and application thereof | |
| CN110156822A (en) | A kind of naphthols-phenylboronic acid compound and its preparation method and application | |
| TW200538140A (en) | Compounds isolated from gamboge resin having activity in inhibiting the growth of tumor/cancer cells and pharmaceutical compositions comprising the same | |
| CN104523664A (en) | Curcumin antineoplastic drug and application thereof | |
| CN101805338A (en) | Oxadiazole-based piperazine derivative and application thereof | |
| CN109535068B (en) | Pyridine substituted chalcone compound or pharmaceutically acceptable salt thereof, and preparation method and application thereof | |
| CN104098457B (en) | Tetrahydrocurcumin analogue, preparation and application thereof | |
| CN107266431A (en) | Herba Peperomiae pellucidae element E or derivatives thereof and application thereof | |
| CN103304573B (en) | Narcissine compounds is preparing the application of antitumor drug | |
| CN106928074B (en) | Isopropanolamine replaces beta-elemene derivatives and its preparation method and application | |
| CN109896986A (en) | The structure of lignanoids natural products 4-O- methyl saururus chinensis alcohol simplifies object, preparation method and its pharmaceutical composition and purposes | |
| CN109897022A (en) | Lactone derivatives, its pharmaceutical composition and its preparation method and application with a smile | |
| CN105622704A (en) | Preparation method and application of antitumor drug X-TOA | |
| CN110028480B (en) | 4, 7-position split melphalan nitrogen mustard derivative of brefeldin A and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20171020 |
|
| WW01 | Invention patent application withdrawn after publication |