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WO2019093699A1 - Sélénopsammapline a et dérivé de celle-ci, procédé de préparation associé, et composition pour la prévention ou le traitement du cancer les contenant en tant que principes actifs - Google Patents

Sélénopsammapline a et dérivé de celle-ci, procédé de préparation associé, et composition pour la prévention ou le traitement du cancer les contenant en tant que principes actifs Download PDF

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Publication number
WO2019093699A1
WO2019093699A1 PCT/KR2018/012826 KR2018012826W WO2019093699A1 WO 2019093699 A1 WO2019093699 A1 WO 2019093699A1 KR 2018012826 W KR2018012826 W KR 2018012826W WO 2019093699 A1 WO2019093699 A1 WO 2019093699A1
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Prior art keywords
hydroxyimino
propanamide
ethyl
phenylthio
bis
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Ceased
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PCT/KR2018/012826
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English (en)
Korean (ko)
Inventor
박형근
이상국
한혜주
변웅섭
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SNU R&DB Foundation
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Seoul National University R&DB Foundation
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Priority claimed from KR1020180128557A external-priority patent/KR102083180B1/ko
Application filed by Seoul National University R&DB Foundation filed Critical Seoul National University R&DB Foundation
Priority to EP18875667.0A priority Critical patent/EP3708563B1/fr
Priority to US16/762,685 priority patent/US11629123B2/en
Publication of WO2019093699A1 publication Critical patent/WO2019093699A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C391/00—Compounds containing selenium

Definitions

  • the present invention relates to novel selenosamphilin A having anticancer activity and derivatives thereof, a method for producing the same, and a pharmaceutical composition containing the same as an effective ingredient.
  • Psammaplin A is a marine natural product having a polymer structure in which a monomer having a bromothyrosine structure is linked to a disulfide structure.
  • the samaflirin A has antimicrobial activity, growth inhibitory action of leukemic cell line P388, DNA topoisomerase inhibitory effect, histone deacetylase inhibitory effect, DNA guarase inhibitory effect, panesyl enzyme transfer inhibitory effect, Inhibitory effect, PPAR-gamma activity effect, and growth inhibitory effect of colon cancer cells.
  • the present invention was conceived to solve the above-described problems in the prior art.
  • the present invention provides novel selenosamphilin A and derivatives thereof having anticancer activity and treating them,
  • the present invention has been completed on the basis thereof.
  • an object of the present invention is to provide novel selenosamphilin A having anticancer activity, a derivative thereof, and a pharmaceutically acceptable salt thereof.
  • Another object of the present invention is to provide a novel method for producing selenosamphilin A having an anticancer activity and derivatives thereof.
  • Still another object of the present invention is to provide a pharmaceutical composition for preventing or treating cancer comprising as an active ingredient a novel selenosamphilin A having anticancer activity, a derivative thereof and a pharmaceutically acceptable salt thereof.
  • the present invention provides selenosamphilin A and its derivatives, isomers thereof, or pharmaceutically acceptable salts thereof, represented by the following formulas (1) or (2)
  • X is hydrogen, C 1-5 alkyl, , 1-naphthyl, 2-naphthyl, or 9-anthracenyl;
  • each of R 1 to R 5 is independently hydrogen, nitro, halogen, cyan, hydroxy, dimethylamino, methylsulfonylamide, trifluoromethyl, C 1-5 alkyl, C 1-3 alkoxy, Aryl, phenoxy, or benzyloxy;
  • R 1 to R 5 When any one of R 1 to R 5 is phenoxy or benzyl, the substituent of the aromatic ring may be C 1-3 alkyl, C 1-3 alkoxy, halogen, trifluoromethyl, or t-butyl Lt; / RTI >
  • X is Or 2-naphthyl
  • R 1 , R 2 , and R 5 are each independently hydrogen;
  • R 3 is hydrogen, hydroxy, ethoxy, t-butyl, fluoro, chloro, bromo, nitro, or benzyl;
  • the R 4 may be hydrogen, bromo, chloro, or fluoro, but is not limited thereto.
  • the present invention also relates to a process for preparing a compound represented by the following formula (4) by adding 2,2'-diseleninediyldiethanamine to a compound represented by the following formula (3) And
  • the present invention also relates to a method for producing selenosamphylline A represented by the following formula (2) by adding dithiothreitol to a compound represented by the following formula (1)
  • a process for the preparation of maphilin A and its derivatives is provided:
  • the present invention also provides a pharmaceutical composition for preventing or treating cancer, comprising selenosamphilin A and its derivatives represented by the above-mentioned formulas (1) and (2), an isomer thereof or a pharmaceutically acceptable salt thereof as an active ingredient .
  • the cancer may be lung cancer or colon cancer.
  • the selenosamphilin A and derivatives thereof may be selected from the group consisting of the following compounds:
  • the present invention provides a method for preventing or treating cancer, comprising the step of administering the pharmaceutical composition to a subject.
  • the present invention provides the use of the pharmaceutical composition for the prevention or treatment of cancer.
  • the present invention provides a novel compound selenosamphilin A and a derivative thereof in which a disulfide moiety is substituted with diselenide according to a structural activity study with respect to semapillin A, which is known to inhibit the growth of cancer cells.
  • the selenosamapillin A And its derivatives exhibit excellent anticancer activity against various human cancer cells and have a superior growth inhibitory effect as compared with existing samaplirin A.
  • the novel compounds are useful as pharmaceutical compositions for cancer prevention and treatment It is expected that it can be used.
  • Fig. 1 shows the structure of a novel selenosamphilin A of the present invention and derivatives thereof.
  • Fig. 1 (a) shows the structure of selenosamphilin A of the formula (1) and its derivatives, ≪ / RTI > shows the structure of a leucine A derivative.
  • FIG. 2 is a view showing a process for producing selenosamphilin A and its derivatives.
  • FIG. 3 is a diagram showing chemical structures of selenosamphilin A and its derivatives prepared by the method of the present invention.
  • the present invention provides novel selenosamphilin A and derivatives thereof having anticancer activity, isomers thereof, pharmaceutically acceptable salts thereof, and compositions for preventing or treating cancer comprising the same as an active ingredient.
  • the compounds according to the present invention inhibit the growth of cancer cells and have a prophylactic or therapeutic effect against cancer, and thus they can be usefully used for the prevention or treatment of cancer.
  • the present invention provides selenosamphilin A represented by the following general formula (1) or (2), a derivative thereof, an isomer thereof or a pharmaceutically acceptable salt thereof.
  • X is hydrogen, C 1-5 alkyl, , 1-naphthyl, 2-naphthyl, or 9-anthracenyl;
  • each of R 1 to R 5 is independently hydrogen, nitro, halogen, cyan, hydroxy, dimethylamino, methylsulfonylamide, trifluoromethyl, C 1-5 alkyl, C 1-3 alkoxy, Aryl, phenoxy, or benzyloxy;
  • R 1 to R 5 When any one of R 1 to R 5 is phenoxy or benzyl, the substituent of the aromatic ring may be C 1-3 alkyl, C 1-3 alkoxy, halogen, trifluoromethyl, or t-butyl Lt; / RTI >
  • X is Or 2-naphthyl;
  • R 1 , R 2 , and R 5 are each independently hydrogen;
  • R 3 is hydrogen, hydroxy, ethoxy, t-butyl, fluoro, chloro, bromo, nitro, or benzyl;
  • R 4 may be hydrogen, bromo, chloro, or fluoro.
  • " C 1-5 alkyl " used in the present invention means a monovalent alkyl group having 1 to 5 carbon atoms, and " C 1-3 alkyl " means a monovalent alkyl group having 1 to 3 carbon atoms.
  • the term includes functional groups such as methyl, ethyl, n - propyl, i - propyl, n - butyl, i - butyl, tert - butyl, n - hexyl and the like.
  • alkyls described in the present invention include both straight chain and branched forms.
  • C 1-3 alkoxy as used in the present invention means an -OR group, wherein R means " C 1 -C 3 alkyl ".
  • Preferred alkoxy groups include, for example, methoxy, ethoxy, phenoxy, and the like.
  • Substituents comprising alkyl, alkoxy and other alkyl moieties described in this invention include both straight chain and branched forms.
  • Preferred embodiments of the selenosamphilin A and derivatives thereof represented by the formula (1) or (2) according to the present invention are as follows:
  • (3,4-dichlorophenyl) -2- (hydroxyimino) propanamide) (((2E, 2'E) -N, N'- (decenylene diyl bis 2E, 2'E) -N, N '- (diselenediylbis (ethane-2,1-diyl) bis (3- (3,4-dichlorophenyl) -2- (hydroxyimino) propanamide), SSM-9);
  • SSM-1, SSM-2, SSM-3, SSM-4, SSM-10 and SSM-12 may be more preferably used as selenosamphilin A and derivatives thereof represented by Formula 1 according to the present invention.
  • the compound of the present invention can be used in the form of a pharmaceutically acceptable salt.
  • a pharmaceutically acceptable salt acid addition salt formed by a pharmaceutically acceptable free acid is useful.
  • Acid addition salts include those derived from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, and aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates, Dioleate, aromatic acid, aliphatic and aromatic sulfonic acids.
  • Such pharmaceutically innocuous salts include, but are not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate chloride, bromide, Butyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, succinate, maleic anhydride, maleic anhydride, , Sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzene sulfonate, toluene sulfonate, chlorobenzene sulfide Butyrate, glycolate
  • the acid addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving the above compound in an excess amount of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile . It may also be prepared by evaporating a solvent or excess acid in this mixture and then drying or by suction filtration of the precipitated salt.
  • a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile
  • the base may be used to make a pharmaceutically acceptable metal salt.
  • the alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is preferable for the metal salt to produce sodium, potassium or calcium salt.
  • the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable salt (such as silver nitrate).
  • the compounds of the present invention include not only pharmaceutically acceptable salts, but also all salts, isomers, hydrates and solvates which can be prepared by conventional methods.
  • a process for preparing a compound represented by the following formula (3) comprising the steps of: synthesizing a compound represented by the following formula (4) by adding 2,2'-diseleninediyldiethanamine to a compound represented by the following formula And
  • Selenosamphafiline A represented by the following formula ≪ / RTI > can be provided:
  • the present invention provides a method for producing selenosamphilin A, which comprises the step of synthesizing selenosamphilin A represented by the following formula (2) and a derivative thereof by adding dithiothreitol to a compound represented by the following formula
  • a method for producing selenosamphilin A represented by the formula (2) and a derivative thereof can be provided:
  • the compound of formula (3) may be prepared by a method including the following steps, but is not limited to the following method:
  • X is as defined in Formula 1 above.
  • the compound of the formula (1) and the formula (2) is prepared by the reaction according to the reaction scheme 1.
  • the substituted aryl aldehyde type substrate (compound S) is reacted with piperidine and acetic acid catalyst Beta-unsaturated ethyl acetoacetate (Compound 3) by condensation reaction with ethyl acetoacetate (Compound 2) in an existing benzene solvent.
  • Compound 3 is reacted with tributyltin hydride (n-Bu 3 SnH) in a toluene solvent to synthesize ethyl acetoacetate (Compound 4) substituted at the alpha position.
  • butyl nitrite (n-BuONO) is added to Compound 4 in the presence of an ethanolic ethoxide base to synthesize an oxime (Compound 5).
  • Compound 5 was reacted with dihydropyran (DHP) in the presence of p-toluenesulfonic acid (p-TsOH) catalyst to obtain compound 6, which was then hydrolyzed with an aqueous solution of potassium hydroxide (1N-KOH) Respectively.
  • DHP dihydropyran
  • p-TsOH p-toluenesulfonic acid
  • selenosamphilin A and derivatives thereof represented by Formula 1 or Formula 2 were prepared, and the structure was analyzed and confirmed by NMR or Mass spectroscopy (see Examples 1 to 28).
  • the forms of substituents X of the compounds prepared according to Examples 1 to 28 are shown in Table 1 below.
  • the present invention provides a method for preventing or ameliorating cancer comprising selenosamphilin A and its derivatives represented by Formulas (1) and (2), its isomer or a pharmaceutically acceptable salt thereof as an active ingredient Or a pharmaceutical composition for therapeutic use.
  • &quot means any act that inhibits cancer or delays the onset of cancer by administration of the pharmaceutical composition according to the present invention.
  • &quot treatment " refers to any action that improves or alters the symptoms of cancer by the administration of the pharmaceutical composition according to the present invention.
  • Cancer &quot which is a preventive and therapeutic disease caused by the composition of the present invention is classified into diseases in which normal tissue cells proliferate unlimitedly for some reason and continue rapid development regardless of the life phenomenon of the living body or the surrounding tissue state.
  • the cancer in the invention may preferably be lung cancer, or colon cancer, but is not limited to this kind.
  • the anticancer activity against various human cancer cells was evaluated using selenosamphilin A and its derivatives synthesized according to the production method of the present invention (see Example 15), and the compound SSM -1, SSM-2, SSM-3, SSM-4, SSM-10 and SSM-12 showed 20 to 60 times more potent anticancer activity than samapillin A compound, (Etoposide), which is an effective inhibitor of cancer cell growth.
  • the selenosamphilin A and its derivatives, its isomers or pharmaceutically acceptable salts thereof represented by the above-mentioned formulas (1) and (2) according to the present invention are useful as pharmaceuticals for preventing, improving or treating cancer, May be useful as a composition.
  • the pharmaceutical composition according to the present invention may contain, in addition to the active ingredient, a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carriers are those conventionally used at the time of formulation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose But are not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like may be further included.
  • the pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may vary depending on the condition and weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.
  • the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, The sensitivity to the drug, the time of administration, the route of administration and the rate of excretion, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts.
  • the pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, sequentially or concurrently with conventional therapeutic agents, and may be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
  • the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, body weight, absorbency, inactivation rate and excretion rate of the active ingredient in the body, type of disease, 0.001 to 150 mg, preferably 0.01 to 100 mg, per kg of body weight may be administered daily or every other day, or one to three divided doses per day.
  • the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.
  • the present invention provides a method of treating cancer comprising administering the pharmaceutical composition to a subject.
  • the term "individu" refers to a subject in need of treatment for a disease, and more specifically refers to a human or non-human primate, a mouse, a mammal such as a dog, a cat, a horse and a cow.
  • the novel compound selenosamphilin A and its derivatives synthesized in the present invention exhibited excellent growth inhibitory activity against human lung cancer and colon cancer cells, And is expected to be useful as a pharmaceutical composition.
  • selenosamphilin A and derivatives thereof as shown in Fig. 1A are prepared, and the preparation of compounds in Examples 1 to 14 is carried out according to Reaction Scheme 1 (Fig. 2) described above .
  • the synthesis examples of SSM-1 are shown below.
  • selenosamaphyllin A monomer derivatives as shown in Fig. 1B were prepared.
  • the preparation of the compounds was carried out according to Reaction Scheme 1 (Fig. 2) will be.
  • the pH was adjusted to 8.3 with phosphoric acid buffer (2 mL) and dimethylsulfoxide (6 mL)
  • the synthesized selenosamphafiline A (1,133 mg)
  • phenyl disulfide (44.2 mg)
  • dithiothreitol 3.2 mg
  • reaction mixture was diluted with ethyl acetate (50 mL), washed with water (10 mL x 10), and distilled under reduced pressure. The residue was separated by column chromatography to give a mixture of selenosamphafilin A monomer (SSM- mg).
  • Nuclear magnetic resonance spectra (1H and 13C NMR) were recorded using a DMSO-d 6 , CD 3 OD, CDCl 3 solution in an 800-MHz Bruker Avance III HD spectrometer with a 5-mm triple resonance inverse (TCI) CryoProbe spectrometer And the chemical shift is expressed in parts per million (ppm).
  • the resonance pattern is represented by s (singlet), d (doublet), t (triplet), q (quartet), quint Is used.
  • the coupling constant (J) is expressed in hertz (Hz).
  • SSM-3 was obtained by using 3-fluoro-4-hydroxybenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 24%).
  • SSM-5 was obtained by using 4-fluorobenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 32%).
  • SSM-6 was obtained using 4-chlorobenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 18%).
  • SSM-8 was obtained by using 3,5-difluorobenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 22%).
  • SSM-10 was obtained by using 4-ethoxybenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 27%).
  • SSM-12 was obtained by using 4-nitrobenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 29%).
  • SSM-13 was obtained by using 4-tert-butoxybenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 19%).
  • SSM-14 was obtained by using 4-2'-naphthylbenzaldehyde as a starting material according to the method of Scheme 1 above. (Total yield: 27%).
  • SSM-15 was obtained using selenosamapline A (1) as a starting material according to the method of Scheme X above. (Total yield: 56%).
  • SSM-18 was obtained using the selenosamphlin A derivative (4) as a starting material according to the method of Scheme X above. (Total yield: 37%).
  • SSM-23 was obtained using the selenosamphlin A derivative (9) as a starting material according to the method of Scheme X above.
  • A549 and HCT116 cells were incubated with 10% fetal bovine serum (FBS, 100 units / mL penicillin, 100 ⁇ g / mL streptomycin and 250 ng / mL amphotericin ratio 1 to 2 times per week at 37 ° C, 5% CO 2 , using a Roswell Park Memorial Institute (RPMI) medium 1640, RPMI 1640) containing amphotericin B All cells were lysed from liquid nitrogen and then used in the experiment after passage over 3 times.
  • FBS fetal bovine serum
  • penicillin 100 ⁇ g / mL
  • streptomycin 100 ⁇ g / mL streptomycin
  • 250 ng / mL amphotericin ratio 1 to 2 times per week at 37 ° C, 5% CO 2
  • RPMI Roswell Park Memorial Institute
  • the lung cancer and colon cancer cell lines used in the present invention were subcultured in RPMI medium containing 10% FBS, 1% PSF, etc., and 10 ⁇ l of a sample dissolved in 10% DMSO in each well of a 96- 190 ⁇ l (5 ⁇ 10 4 cells / ml) of the cell suspension was added and cultured for 3 days. 190 ⁇ l of the cell suspension was added to at least 16 wells and incubated for 30 minutes, and used as a zero-day control before the experiment. The cultured cells were fixed with 10% TCA (trichloroacetic acid), stained with SRB solution, dissolved in 10 mM Tris-base, and then absorbed at 515 nm. 10% DMSO was used as a control, and the cell survival rate according to the treatment of each test substance was measured using the following equation (1).
  • TCA trichloroacetic acid
  • the value of the sample treatment group was expressed as a percentage of the control group, and the treatment of each test substance was calculated by the mean value ⁇ SEM of the double or triple test.
  • the IC 50 value is the concentration of the test substance relative to the 50% survival rate.
  • the present invention confirms excellent anticancer activity against various human cancer cells of novel selenosamphilin A and its derivatives and a superior growth inhibitory effect as compared with existing samaplirin A.
  • the novel compounds of the present invention are useful for prevention and treatment of cancer, It is expected that it can be usefully used as a pharmaceutical composition for treatment.

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Abstract

La présente invention concerne : de nouvelles sélénopsammapline A et un dérivé de celle-ci, qui ont une activité anticancéreuse ; un procédé de préparation associé ; et une composition pharmaceutique les contenant en tant que principes actifs et, plus particulièrement : un nouveau composé de sélénopsammapline A et un dérivé de celui-ci qui présentent une excellente activité anticancéreuse, étant donné qu'une fraction disulfure correspondante est substituée par du diséléniure selon la recherche sur l'activité structurale de la psammapline A, qui est connue pour avoir un effet d'inhibition de la croissance de cellules cancéreuses ; un procédé de préparation associé ; et une composition pour prévenir ou traiter le cancer, contenant ceux-ci en tant que principes actifs. La nouvelle séléopsammapline A et le dérivé de celle-ci, selon la présente invention présentent une excellente activité anticancéreuse sur diverses lignées de cellules cancéreuses humaines et sont destinés à être utilisés de manière efficace dans une composition pharmaceutique pour la prévention et le traitement du cancer.
PCT/KR2018/012826 2017-11-09 2018-10-26 Sélénopsammapline a et dérivé de celle-ci, procédé de préparation associé, et composition pour la prévention ou le traitement du cancer les contenant en tant que principes actifs Ceased WO2019093699A1 (fr)

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EP18875667.0A EP3708563B1 (fr) 2017-11-09 2018-10-26 Sélénopsammapline a et dérivé de celle-ci, procédé de préparation associé, et composition pour la prévention ou le traitement du cancer les contenant en tant que principes actifs
US16/762,685 US11629123B2 (en) 2017-11-09 2018-10-26 Selenopsammaplin A and derivative thereof, preparation method therefor, and composition for preventing and treating cancer, containing same as active ingredients

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KR20170148790 2017-11-09
KR10-2018-0128557 2018-10-25
KR1020180128557A KR102083180B1 (ko) 2017-11-09 2018-10-25 셀레노사마필린 a와 그 유도체, 이의 제조방법, 및 이를 유효성분으로 포함하는 암 예방 및 치료용 조성물

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115925675A (zh) * 2022-11-10 2023-04-07 中国海洋大学 一种Psammaplin A类衍生物及其制备方法和应用

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KR20140141904A (ko) * 2013-06-03 2014-12-11 서울대학교산학협력단 신규한 항암활성을 갖는 사마필린a 유도체 및 이를 함유하는 약학적 조성물
KR20160125989A (ko) * 2014-03-14 2016-11-01 올텍 법인회사 셀레노유기 화합물의 조성물 및 이의 사용 방법

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