WO2020192348A1 - Dérivé de phénylallylidène cyclohexénone, procédé de préparation et utilisation - Google Patents

Dérivé de phénylallylidène cyclohexénone, procédé de préparation et utilisation Download PDF

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WO2020192348A1
WO2020192348A1 PCT/CN2020/076878 CN2020076878W WO2020192348A1 WO 2020192348 A1 WO2020192348 A1 WO 2020192348A1 CN 2020076878 W CN2020076878 W CN 2020076878W WO 2020192348 A1 WO2020192348 A1 WO 2020192348A1
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och
preparation
cancer
allyl
cinnamaldehyde
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PCT/CN2020/076878
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Chinese (zh)
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凌勇
杨圣菊
张延安
刘季
凌长春
李洋阳
刘思群
贾启新
明古旭
吴红梅
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南通大学
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Priority to AU2020213346A priority Critical patent/AU2020213346B2/en
Publication of WO2020192348A1 publication Critical patent/WO2020192348A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/22—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/40—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by doubly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/657—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings
    • C07C49/683—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings having unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/687—Unsaturated compounds containing a keto groups being part of a ring containing halogen
    • C07C49/697—Unsaturated compounds containing a keto groups being part of a ring containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/12—Acetic acid esters
    • C07C69/14—Acetic acid esters of monohydroxylic compounds
    • C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
    • C07C69/157—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the present invention relates to the field of biomedicine, in particular to a class of phenyl allyl cyclohexenone derivatives and preparation methods, pharmaceutical compositions containing these derivatives and pharmaceutical applications with TrxR inhibitory activity, especially in preparation Application of anti-tumor drugs.
  • the World Health Organization (WHO) report shows that malignant tumors have long become one of the world's major diseases and are rapidly becoming the world's number one "killer disease", seriously threatening human health and lives.
  • WHO statistics in the past 30 years, the world cancer incidence rate has increased at an average annual rate of 3-5% and it is expected that by 2020, the world cancer incidence rate will increase by 50% compared to 2008, that is, 15 million new cancer patients will be added every year . Not only that, the global death toll from cancer is also rising rapidly, and it has become the world's number one deadly disease. And it is estimated that by 2030, the global cancer deaths will reach 13.2 million. Cancer has become a global challenge and problem, and the fight against cancer has a long way to go.
  • ROS Reactive oxygen species
  • ROS can be divided and non-radical type radical, wherein the radical type mainly containing superoxide anion (O 2 -), hydroxyl radical (HO ⁇ ) and the like, non-radical type ROS are mainly hydrogen peroxide (H 2 O 2 ), ozone (O 3 ), pernitrate, etc.
  • ROS scavenging systems exist in cells, such as superoxide dismutase (SOD1, SOD2, SOD3), glutathione peroxidase, catalase (CAT) and glutathione Peptides (GSH), glutaredoxin, antioxidant proteins (peroxiredoxins) and thioredoxins, etc., can make the production and elimination of ROS in the body reach a dynamic balance, so that the normal functions of cells are not affected (Trachootham D, Alexandre J, Huang P. Nature Reviews Drug Discovery, 2009, 8, 579-591). It has been reported that ROS levels increase in a variety of cancer cells.
  • leukemia cells isolated from blood samples of patients with chronic lymphocytic leukemia or hairy cell leukemia have increased ROS production compared with normal lymphocytes (Zhou Y, Hileman EO, Plunkett W, et al. Blood, 2003, 101, 4098-4104).
  • the level of oxidative damage products such as oxidized DNA bases and lipid peroxides in solid tumors increases.
  • piperamide is targeted to regulate thioredoxin protease (TrxR) to regulate the redox effect and the dynamic balance of reactive oxygen species, resulting in a decrease in the level of GSH in tumor cells, an increase in GSSG levels, and ultimately an increase in the concentration of ROS in tumor cells. High, causing apoptosis or necrosis.
  • TrxR thioredoxin protease
  • piperamide has good anti-tumor activity, but it also has some shortcomings that limit its clinical application.
  • the activity of piper amide is not high enough, and the specific mechanism of action has not been fully elucidated; secondly, the raw materials of piper amide extracted from plants are limited, and the medicinal resources needed for production are quite consumed; in addition, the artificially synthesized piper amide, its The preparation process is complex, requires expensive metal catalysts, and the reaction yield is low. Therefore, it is necessary to carry out structural derivatization and structural optimization of piperamide, and then screen out anti-tumor compounds with strong targeting, high efficiency, low toxicity, and easy synthesis.
  • the present invention designs and synthesizes a novel phenyl allyl cyclohexenone derivative with TrxR inhibitory activity based on the structural characteristics of piper amide, taking into account the biological activity, drug-making properties, and ease of synthesis, and retains PL active sites
  • the C2-C3 double bond and C7-C8 double bond not only have significant inhibitory activity on a variety of human tumor cells and drug-resistant tumor cells, but also have less damage to normal cells and can selectively kill tumor cells.
  • the preliminary research mechanism shows that the compound of the present invention can inhibit TrxR enzyme activity, increase the level of ROS in tumor cells, cause tumor cell membrane damage, induce tumor cell apoptosis, and promote the anti-tumor activity of the compound of the invention.
  • R represents one or more substituents on the benzene ring, selected from H, hydroxyl, halogen group, amino, nitro, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamine
  • substituents on the benzene ring selected from H, hydroxyl, halogen group, amino, nitro, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamine
  • X represents H, halogen group, CN or C1-C6 alkyl group.
  • the R represents H, Br, NO 2 , OCH 3 , F, CH 3 , Cl, N(CH 3 ) 2 , OH, O(CH 2 ) 2 OCH 3 , O(CH 2 ) 2 O( One or more of CH 2 ) 2 OCH 3 or OAc.
  • the substitution position of the R on the benzene ring is one or more of the 2, 3, and 4 positions.
  • the R represents H, 4-F, 4-Cl, 4-Br, 2-NO 2 , 4-NO 2 , 3-OH, 2-OCH 3 , 4-OCH 3 , 4-CH 3 , 3-CH 3 , 4-N(CH 3 ) 2 , 4-OH-3-OCH 3 , 4-OAc-3-OCH 3 , 3-O(CH 2 ) 2 OCH 3 , 3-OCH 3 -4- O(CH 2 ) 2 OCH 3 , 3-OCH 3 -4-O(CH 2 ) 2 O(CH 2 ) 2 OCH 3 , X represents H, Cl, Br, CN, CH 3 .
  • Another object of the present invention is to provide a preparation method of the compound of general formula I of the present invention, as follows:
  • R represents one or more substituents on the benzene ring, selected from H, hydroxyl, halogen group, amino, nitro, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, One or more of C1-C6 acyloxy and C1-C6 methoxy ethers;
  • X represents H, halogen group, CN or C1-C6 alkyl.
  • the R represents H, Br, NO 2 , OCH 3 , F, CH 3 , Cl, N(CH 3 ) 2 , OH, O(CH 2 ) 2 OCH 3 , O(CH 2 ) 2 O( One or more of CH 2 ) 2 OCH 3 or OAc.
  • the substitution position of the R on the benzene ring is one or more of the 2, 3, and 4 positions.
  • the R represents H, 4-F, 4-Cl, 4-Br, 2-NO 2 , 4-NO 2 , 3-OH, 2-OCH 3 , 4-OCH 3 , 4-CH 3 , 3-CH 3 , 4-N(CH 3 ) 2 , 4-OH-3-OCH 3 , 4-OAc-3-OCH 3 , 3-O(CH 2 ) 2 OCH 3 , 3-OCH 3 -4- O(CH 2 ) 2 OCH 3 , 3-OCH 3 -4-O(CH 2 ) 2 O(CH 2 ) 2 OCH 3 , X represents H, Cl, Br, CN, CH 3 .
  • the catalyst is selected from one or more of triphenylphosphorus, TiCl 4 , trimethylsilimidazole (TMSI), and magnesium hydrogen sulfate.
  • TMSI trimethylsilimidazole
  • magnesium hydrogen sulfate magnesium hydrogen sulfate
  • the synthetic route is as follows:
  • Another object of the present invention is to provide the application of the cyclohexenone derivatives of the present invention in the preparation of drugs with TrxR inhibitory activity.
  • the drug with TrxR inhibitory activity becomes a drug for treating and/or preventing cancer.
  • the cancer is selected from liver cancer, colon cancer, gastric cancer, breast cancer or cervical cancer.
  • the compound of the present invention can be formulated alone or in combination with one or more pharmaceutically acceptable carriers to provide medicine.
  • solvents, diluents, etc. can also be used for oral administration dosage forms, such as capsules, dispersible powders, tablets, granules, etc.
  • Various dosage forms of the pharmaceutical composition of the present invention can be prepared according to methods well known in the pharmaceutical field. These pharmaceutical preparations may contain, for example, 0.05% to 90% by weight of the active ingredient in combination with the carrier, and more commonly about 15% to 60% by weight of the active ingredient.
  • the dosage of the compound of the present invention can be 0.005-5000 mg/kg/day, and the dosage can also exceed this dosage range according to the severity of the disease or the different dosage forms.
  • the compound of the present invention can self-assemble into nanoparticles to improve activity alone, or be combined with other anti-tumor drugs such as alkylating agents (such as cyclophosphamide or chlorambucil), antimetabolites (such as 5-fluorouracil or hydroxyurea), topological Isomerase inhibitors (such as camptothecin), mitotic inhibitors (such as paclitaxel or vinblastine), DNA inserters (such as doxorubicin) combined with self-assembled nanoparticles to improve activity, and can also be combined with radiotherapy.
  • anti-tumor drugs such as alkylating agents (such as cyclophosphamide or chlorambucil), antimetabolites (such as 5-fluorouracil or hydroxyurea), topological Isomerase inhibitors (such as camptothecin), mitotic inhibitors (such as paclitaxel or vinblastine), DNA inserters (such as doxorubicin) combined with self-assembled nanoparticles to improve activity,
  • the invention combines the structural characteristics, structure-activity relationship and pharmacophore model of the anti-tumor drug piperamide, based on the piperamide, uses the theory of bioelectronic isosteres, and uses cinnamaldehyde with different substituents as raw materials to design and synthesize New phenyl allyl cyclohexenone derivatives with TrxR inhibitory activity have been developed to simplify their synthetic route and facilitate mass production. They have studied their inhibitory effects on TrxR targets and malignant tumor cells. A variety of tumor cells (including liver cancer, breast cancer, gastric cancer, colon cancer, cervical cancer, etc.) have a strong and selective inhibitory effect on the proliferation, and can significantly inhibit TrxR enzyme activity.
  • the compound of the present invention has a certain concentration of Normal cells are less damaged, and can induce the expression of ROS in tumor cells, and coordinately promote tumor cell apoptosis or necrosis.
  • the I 8 spectrum data is: ESI-MS (m/z): 229[M+H] + ; 1 H NMR (DMSO-d 6 , 400MHz): ⁇ 7.46 (m, 2H, Ar-H), 7.28 (m, 1H, CH), 7.04 (m, 2H, Ar-H), 6.96 (m, 1H, CH), 6.94 (m, 1H, CH), 6.91 (m, 1H, CH), 6.21 (m, 1H, CH), 2.91 (m, 2H, CH 2 ), 2.48 (m, 2H, CH 2 ).
  • Example 2 Using MTT method to determine the inhibition rate of tumor cell and normal cell proliferation of the compound of the present invention
  • the anti-proliferative activity of the compound of the present invention on four human cancer cell lines was evaluated by using the tetramethylazole blue colorimetry (MTT) in vitro anti-tumor test.
  • Piperamine (PL) was used as a positive control drug.
  • Human cancer cell lines liver cancer cell SMMC7721, colon cancer cell HCT116, gastric cancer cell HGC-27, human cervical cancer cell Hela, human normal cell: human gastric mucosal epithelial cell GES-1.
  • the experimental method is as follows: Take a bottle of cells that are in good condition in the exponential growth phase, add 0.25% trypsin to digest, make the adherent cells fall off, and prepare a suspension containing 2 ⁇ 10 4 to 4 ⁇ 10 4 cells per ml.
  • the cell suspension was inoculated on a 96-well plate, 180 ⁇ L per well, and placed in a constant temperature CO 2 incubator for 24 hours. Change the liquid, add test compounds I 1 -I 20 (compounds are dissolved in DMSO and then diluted with PBS, the concentration of test compound is 12.5 ⁇ M), 20 ⁇ L per well, and incubated for 72 hours. Add MTT to a 96-well plate, 20 ⁇ L per well, and react in an incubator for 4 hours.
  • Cell inhibition rate (OD value of negative control group-OD value of test substance group)/OD value of negative control group ⁇ 100%.
  • the compound of the present invention has undergone a series of tumor cell anti-proliferation activity tests.
  • the results of pharmacological experiments show (see Table 2) that the compound I 1 -I 20 of the present invention has a strong inhibitory effect on the proliferation of most tumor cells at a concentration of 12.5 ⁇ M.
  • the inhibitory activity of some compounds was significantly better than that of the positive control drug pyramine (PL).
  • the compounds I 1 to I 20 of the present invention are significantly less cytotoxic to human normal gastric mucosal cells GES-1 at the same concentration than tumor cells, indicating that the compounds of the present invention not only have significant anti-tumor activity on tumor cells, but also Low cytotoxicity and certain tumor cell selectivity.
  • the ROS-Glo hydrogen peroxide test method measures ROS changes by directly detecting H 2 O 2 levels in cells.
  • the cells were seeded into a 96-well cell culture plate and cultured with the test drug (0.01-12.5 ⁇ M) for 24 hours.
  • I 4 to I 8 , I 11 to I 15 , I 18 , and I 19 among the compounds of general formula I of the present invention are selected as representatives, and the ROS levels in tumor cells are tested.
  • DCFH-DA was used as a fluorescent probe to determine the changes of ROS in human cervical cancer Hela cells after drug treatment. The changes in fluorescence intensity can quantitatively reflect the intracellular ROS levels.
  • the results show that the compounds I 4 ⁇ I 8 , I 11 ⁇ I 15 , I 18 , and I 19 of the present invention can significantly increase the ROS content in Hela cells at 12.5 ⁇ M, which is 3.7 to 8.9 times that of the control group, which is better than the positive control drug PL (3.2 times the control group).
  • TrxR activity test kit BioVision, Milpitas, CA, USA. Simply put, the cell line is dissolved in a centrifuge tube with 1x buffer solution and then ice-bathed for 20 minutes, and then centrifuged at 10,000 ⁇ g 4°C for 15 minutes. The supernatant is transferred to a new centrifuge tube, and the protein concentration is calculated by the Bio-Rad protein test method. The sample is diluted to 2X working concentration with buffer solution. Prepare two wells (with and without inhibitor) for each sample in triplicate. The reaction buffer and the reaction buffer with inhibitors were prepared according to the instructions. Before reading, use the BioTek Synergy HT multi-mode microplate reader to measure the absorbance at 412nm wavelength every 20 seconds within 5 minutes after shaking.
  • the experimental results show that compounds I 1 to I 20 have significant inhibitory activity on TrxR at a concentration of 12.5 ⁇ M.
  • the inhibitory activity data are shown in Table 3. Most of the compounds show stronger or comparable inhibitory activity than the positive control drug stubmenine The activity indicates that the phenylallyl cyclohexenone derivative of the present invention has good TrxR inhibitory activity, which is consistent with its anti-tumor activity.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des dérivés de phénylallylidène cyclohexénone ayant la structure représentée dans la formule générale I. L'invention utilise une combinaison avec des caractéristiques structurales et une relation structure-fonction de piplartine, le remplacement des liaisons amino par des liaisons doubles, et la réservation de groupes actifs, ce qui permet de modifier des substituants aromatiques, et de concevoir de nouveaux dérivés de phénylallylidène cyclohexénone ciblant la thiorédoxine réductase (TrxR) pour la surexpression de tissu tumoral. L'invention permet de résoudre des problèmes se rapportant à des défauts de multiples étapes de synthèse de piplartine et une exigence pour des catalyseurs métalliques onéreux, l'invention permet d'améliorer en outre l'activité antitumorale des composés. Des résultats de recherche indiquent que les composés ont des effets d'inhabitation forts sur la prolifération de cellules tumorales et peuvent augmenter de manière significative le niveau ROS dans les cellules tumorales et améliorer leur effet antitumoral.
PCT/CN2020/076878 2019-03-22 2020-02-27 Dérivé de phénylallylidène cyclohexénone, procédé de préparation et utilisation WO2020192348A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114904012A (zh) * 2021-07-22 2022-08-16 四川大学华西医院 一种活性氧自补充的两亲性嵌段共聚物-药物偶联物、其制备方法及其用途

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110002987B (zh) * 2019-03-22 2020-09-15 南通大学 苯基亚烯丙基环己烯酮衍生物及制备方法和用途
CN113336631B (zh) * 2021-06-10 2022-12-02 南开大学 人工合成钯纳米酶催化含有酚羟基连接的化合物的应用
CN116375672B (zh) * 2023-02-21 2024-06-25 广州医科大学 香豆素丙烯醛衍生物及其制备方法和在制备抗肿瘤药物中的应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102625805A (zh) * 2009-09-02 2012-08-01 堪瑟拉治疗有限公司 治疗癌症的化合物和组分
WO2016014625A1 (fr) * 2014-07-22 2016-01-28 Board Of Trustees Of The University Of Arkansas Compositions et procédés de déplétion sélective de cellules sénescentes
CN106673988A (zh) * 2016-12-05 2017-05-17 南通大学 苄亚基环己烯酮衍生物及其制备方法和医药用途
CN110002987A (zh) * 2019-03-22 2019-07-12 南通大学 苯基亚烯丙基环己烯酮衍生物及制备方法和用途

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102625805A (zh) * 2009-09-02 2012-08-01 堪瑟拉治疗有限公司 治疗癌症的化合物和组分
WO2016014625A1 (fr) * 2014-07-22 2016-01-28 Board Of Trustees Of The University Of Arkansas Compositions et procédés de déplétion sélective de cellules sénescentes
CN106673988A (zh) * 2016-12-05 2017-05-17 南通大学 苄亚基环己烯酮衍生物及其制备方法和医药用途
CN110002987A (zh) * 2019-03-22 2019-07-12 南通大学 苯基亚烯丙基环己烯酮衍生物及制备方法和用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHANG, HSUN-SHUO ET AL.: "Antiproliferation of Cryptocarya concinna-derived cryptocaryone against oral cancer cells involving apoptosis, oxidative stress, and DNA damage.", BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE., no. 16, 31 December 2016 (2016-12-31), XP055737391, ISSN: 1472-6882, DOI: 20200527142605A *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114904012A (zh) * 2021-07-22 2022-08-16 四川大学华西医院 一种活性氧自补充的两亲性嵌段共聚物-药物偶联物、其制备方法及其用途
CN114904012B (zh) * 2021-07-22 2023-12-15 四川大学华西医院 一种活性氧自补充的两亲性嵌段共聚物-药物偶联物、其制备方法及其用途

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