RU2758670C1 - New chemical compound of 5-fluorouracil and doxorubicin - Google Patents
New chemical compound of 5-fluorouracil and doxorubicin Download PDFInfo
- Publication number
- RU2758670C1 RU2758670C1 RU2020144099A RU2020144099A RU2758670C1 RU 2758670 C1 RU2758670 C1 RU 2758670C1 RU 2020144099 A RU2020144099 A RU 2020144099A RU 2020144099 A RU2020144099 A RU 2020144099A RU 2758670 C1 RU2758670 C1 RU 2758670C1
- Authority
- RU
- Russia
- Prior art keywords
- fluorouracil
- doxorubicin
- chemical compound
- new chemical
- compound
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 11
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 title claims description 14
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 title claims description 8
- 229960002949 fluorouracil Drugs 0.000 title claims description 8
- 229960004679 doxorubicin Drugs 0.000 title claims description 7
- 230000000694 effects Effects 0.000 abstract description 4
- 238000011275 oncology therapy Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 7
- 230000006820 DNA synthesis Effects 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000005497 Thymidylate Synthase Human genes 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000003817 anthracycline antibiotic agent Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000003093 intracellular space Anatomy 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Предлагаемое изобретение относится к химии, фармацевтике и медицине, а именно к новому химическому соединению, которое можно применять в клинической практике терапии онкологических заболеваний.The proposed invention relates to chemistry, pharmaceuticals and medicine, namely to a new chemical compound that can be used in clinical practice for the treatment of cancer.
Доксорубицин и 5-фторурацил являются широко используемыми лекарственными средствами в клинической практике терапии онкологических заболеваний. Зачастую схемы противоопухолевой химиотерапии включают комбинации этих двух препаратов (Тюляндин С.А. Химиотерапия диссеминированного рака молочной железы. Практическая онкология. 2000,2: 3-11), Fassati R, Confaloneri C, Torri V, et al: Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31510 women. J. Clin. Oncol. 1988, 16:3439-3460.).Doxorubicin and 5-fluorouracil are widely used drugs in the clinical practice of cancer therapy. Often, anticancer chemotherapy regimens include combinations of these two drugs (Tyulandin S.A. Chemotherapy for disseminated breast cancer. Practical oncology. 2000.2: 3-11), Fassati R, Confaloneri C, Torri V, et al: Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31510 women. J. Clin. Oncol. 1988, 16: 3439-3460.).
Однако использование их одновременно невозможно вследствие взаимодействия лекарственных форм и инактивации лекарственных средств. Коммерческий препарат 5-фторурацила вследствие малой растворимости в воде выпускается в виде щелочного раствора. Доксорубицин не совместим со щелочной средой. Происходит инактивация препарата, что проявляется визуально изменением окраски от красного до синего цвета. Поэтому использование этих двух препаратов в схемах комбинированной терапии должно быть разграничено по времени.However, their use at the same time is impossible due to the interaction of dosage forms and drug inactivation. The commercial preparation of 5-fluorouracil, due to its low solubility in water, is available in the form of an alkaline solution. Doxorubicin is not compatible with an alkaline environment. Inactivation of the drug occurs, which is manifested visually by a color change from red to blue. Therefore, the use of these two drugs in combination therapy regimens should be separated in time.
Доксорубицин представляет собой антрациклиновый антибиотик I класса, который подавляет синтез ДНК и РНК. Механизм действия: встраивание между двумя соседними нуклеотидами, в результате которого образуется прочное взаимодействие между ДНК и антрациклиновым кольцом, благодаря чему нарушается синтез ДНК и транскрипция и ингибирование фермента топоизомеразы II в синтезе ДНК.Doxorubicin is a class I anthracycline antibiotic that inhibits DNA and RNA synthesis. Mechanism of action: insertion between two adjacent nucleotides, resulting in a strong interaction between DNA and the anthracycline ring, thereby disrupting DNA synthesis and transcription and inhibition of the enzyme topoisomerase II in DNA synthesis.
5-фторурацил активный метаболит, действие которого связано с ингибированием процесса деления клеток путём блокирования синтеза ДНК за счет угнетения активности фермента тимидилатсинтетазы) и образования структурно несовершенной РНК (вследствие внедрения 5-фторурацла в ее структуру).5-fluorouracil is an active metabolite, the action of which is associated with inhibition of the process of cell division by blocking DNA synthesis by inhibiting the activity of the enzyme thymidylate synthetase) and the formation of structurally imperfect RNA (due to the introduction of 5-fluorouracl into its structure).
Задачей изобретения является получение нового химического соединения повышающего эффективность терапии и снижающего лекарственную нагрузку. The objective of the invention is to obtain a new chemical compound that increases the effectiveness of therapy and reduces the drug load.
Технический результат - получение соединения, позволяющего одновременное использование 5-фторурацила и доксорубицина. EFFECT: obtaining a compound that allows the simultaneous use of 5-fluorouracil and doxorubicin.
Технический результат достигается тем, что получают новое соединение путем химического присоединения 5-фторурацила к доксорубицину по функциональным группам для возможности разрыва соединения на два самостоятельных фрагмента во внутриклеточном пространстве, соединение выражается формулой:The technical result is achieved by the fact that a new compound is obtained by chemical addition of 5-fluorouracil to doxorubicin by functional groups for the possibility of breaking the compound into two independent fragments in the intracellular space, the compound is expressed by the formula:
Пример. К раствору 5-фторурацила в сухом диметилсульфоксиде на электромагнитной мешалке при температуре 53°С добавляли формальдегид в химически эквивалентном соотношении. Смесь перемешивали при нагревании в течение 3 часов. Затем полученную реакционную смесь добавляли к водному раствору докосрубицина и выдерживали при комнатной температуре в течение суток. После этого полученный продукт очищали трёхкратным диализом против дистилированной воды. Продукт сушили в сушильном шкафу при температуре 45°С. Выход составил 78%. Example. To a solution of 5-fluorouracil in dry dimethyl sulfoxide on an electromagnetic stirrer at a temperature of 53 ° C was added formaldehyde in a chemically equivalent ratio. The mixture was stirred with heating for 3 hours. Then the resulting reaction mixture was added to an aqueous solution of docosrubicin and kept at room temperature for a day. After that, the resulting product was purified by dialysis three times against distilled water. The product was dried in an oven at 45 ° C. The yield was 78%.
Готовый продукт представляет собой аморфный порошок красного цвета, хорошо растворим в воде.The finished product is an amorphous red powder, readily soluble in water.
Потенциальное преимущество использования соединения. Сочетание в одном соединении двух составных частей, обладающих активностью в отношении опухолевых клеток и имеющих различные точки приложения, потенциально способно достичь большей эффективности терапии при снижении лекарственной нагрузки. Potential benefit of using a connection. The combination in one compound of two constituents with activity against tumor cells and having different points of application, potentially can achieve greater effectiveness of therapy while reducing the drug load.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2020144099A RU2758670C1 (en) | 2020-12-30 | 2020-12-30 | New chemical compound of 5-fluorouracil and doxorubicin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2020144099A RU2758670C1 (en) | 2020-12-30 | 2020-12-30 | New chemical compound of 5-fluorouracil and doxorubicin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2758670C1 true RU2758670C1 (en) | 2021-11-01 |
Family
ID=78466753
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2020144099A RU2758670C1 (en) | 2020-12-30 | 2020-12-30 | New chemical compound of 5-fluorouracil and doxorubicin |
Country Status (1)
| Country | Link |
|---|---|
| RU (1) | RU2758670C1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3803124A (en) * | 1968-04-12 | 1974-04-09 | Farmaceutici It Soc | Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives |
| US4299822A (en) * | 1980-06-09 | 1981-11-10 | Sidney Farber Cancer Institute, Inc. | N-Trifluoroacetyladriamycin-14-O-hemiglutarate and -hemiadipate and therapeutic compositions containing same |
| RU2457846C2 (en) * | 2010-07-05 | 2012-08-10 | Александр Анатольевич Зимичев | Method of treatment in case of urinary bladder cancer |
| RU2465924C2 (en) * | 2011-02-09 | 2012-11-10 | Федеральное государственное бюджетное учреждение "Ростовский научно-исследовательский онкологический институт" Министерства здравоохранения и социального развития Российской Федерации | Method of treating breast cancer |
-
2020
- 2020-12-30 RU RU2020144099A patent/RU2758670C1/en active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3803124A (en) * | 1968-04-12 | 1974-04-09 | Farmaceutici It Soc | Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives |
| US4299822A (en) * | 1980-06-09 | 1981-11-10 | Sidney Farber Cancer Institute, Inc. | N-Trifluoroacetyladriamycin-14-O-hemiglutarate and -hemiadipate and therapeutic compositions containing same |
| RU2457846C2 (en) * | 2010-07-05 | 2012-08-10 | Александр Анатольевич Зимичев | Method of treatment in case of urinary bladder cancer |
| RU2465924C2 (en) * | 2011-02-09 | 2012-11-10 | Федеральное государственное бюджетное учреждение "Ростовский научно-исследовательский онкологический институт" Министерства здравоохранения и социального развития Российской Федерации | Method of treating breast cancer |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2015110649A (en) | Hydrochloric acid icotinib, composite, crystallographic form, combined medicine and its application | |
| US20220110941A1 (en) | Combinations for the treatment of neoplasms using quiescent cell targeting and inhibitors of mitosis | |
| CN101787064B (en) | Cytarabine derivatives and purposes thereof in resisting cancers and tumors | |
| AU2017353907A1 (en) | 5-halouracil-modified micrornas and their use in the treatment of cancer | |
| RU2758670C1 (en) | New chemical compound of 5-fluorouracil and doxorubicin | |
| JP2001139476A (en) | Anti-malignant tumor agent to be used for malignant neoplasm including cancer | |
| CN105294649B (en) | A kind of Ceritinib compound and its pharmaceutical composition | |
| CN119280258B (en) | Application of marigold glycoside combined with difatinib or panatinib to blocking esophageal squamous carcinoma progression | |
| CN111356454B (en) | Combination product containing dicycloplatin, preparation method and application thereof | |
| KR20140035974A (en) | Combined pharmaceutical compositions for the treatment of tumours | |
| CN1126538C (en) | Carcinostatics | |
| EP1678189A2 (en) | Process for the preparation of trans- or cis-diammoniumdichlorodihydroxyplatinum(iv) salts and derivatives and their use for the preparation of pharmaceutical active agents | |
| CN1245407C (en) | Composition of garcinolic acid compounds, its preparing process and medical composition using it as active component | |
| TW201211061A (en) | Pharmaceutical composition for treating cancers | |
| CN102115483A (en) | Halogenated dideoxy sugar derivative, preparation method and application thereof | |
| CN101898979B (en) | Phenyl nitrone compounds containing stilbene sections and application thereof | |
| EA011573B1 (en) | Antitumor effect fortifier, antitumor agent and method of therapy for cancer | |
| CN113440615A (en) | Pharmaceutical composition comprising a protein kinase inhibitor and a chemotherapeutic drug and uses thereof | |
| CN116621895B (en) | A flavonoid glycoside and its application in preparing anti-tumor drugs | |
| RU2077885C1 (en) | Antitumor agent for local treatment of malignant tumors | |
| CN1939311B (en) | Ginseng sapogenin aglycone derivative biological preparation and its usage | |
| CN117337284A (en) | Medical use of a CDK4/6 inhibitor | |
| CN120549940A (en) | A combined drug for treating tumors with FGFR3-TACC3 fusion gene and its application | |
| CN110066800A (en) | A kind of application of noval chemical compound and combinations thereof | |
| CN101313931A (en) | Application of Black Ugly Extract in Preparation of Antineoplastic Drugs |