WO2019056376A1 - Dérivé de géfitinib-fluoroboronbipyrrole sensible à l'acide, son procédé de préparation et son utilisation médicale - Google Patents
Dérivé de géfitinib-fluoroboronbipyrrole sensible à l'acide, son procédé de préparation et son utilisation médicale Download PDFInfo
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- WO2019056376A1 WO2019056376A1 PCT/CN2017/103190 CN2017103190W WO2019056376A1 WO 2019056376 A1 WO2019056376 A1 WO 2019056376A1 CN 2017103190 W CN2017103190 W CN 2017103190W WO 2019056376 A1 WO2019056376 A1 WO 2019056376A1
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- Prior art keywords
- cancer
- derivative
- compound
- gefitinib
- acid
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- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
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- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
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- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 229910017604 nitric acid Inorganic materials 0.000 description 1
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- 231100001083 no cytotoxicity Toxicity 0.000 description 1
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- 238000006552 photochemical reaction Methods 0.000 description 1
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- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
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- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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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
- A61K31/69—Boron compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
-
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
Definitions
- the present invention also relates to the use of a compound of the formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, for the preparation of a photodynamic drug or a photosensitizing drug.
- a "pharmaceutically acceptable salt” of a compound is understood to mean a salt which is a pharmaceutically acceptable (as defined herein) salt and which possesses the desired pharmacological activity of the parent compound.
- This salt includes:
- Solid tumors have a slightly acidic environment, such as lung cancer, stomach cancer, esophageal cancer, breast cancer, bladder cancer, prostate cancer, pancreatic cancer, cholangiocarcinoma, rectal cancer, colon cancer, skin cancer, head and neck.
- Solid tumors such as cancer, ocular tumor, uterine cancer and ovarian cancer all have a slightly acidic environment, and the compound disclosed in the present patent or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same can be prepared as a photosensitizing drug for treating the above cancer.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (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
La présente invention concerne un dérivé de géfitinib-fluoroboronbipyrrole lié à un cétal et sensible à un environnement légèrement acide, son procédé de préparation et son utilisation médicale. La structure moléculaire du dérivé est telle que décrite dans la formule (I) de la description. En particulier, la présente invention concerne un dérivé de gefitinib-fluoroboronbipyrrole, son procédé de préparation et une composition pharmaceutique contenant le composé, ainsi que l'utilisation de celui-ci en tant que photosensibilisateur, en particulier l'utilisation dans le traitement de cancers. Dans un environnement de tissu normal, le composé présente une cytotoxicité inférieure, du fait de l'interaction entre le groupe géfitinib et le dérivé de fluoroboronbipyrroline. Cependant, dans l'environnement faiblement acide extracellulaire du tissu tumoral, l'hydrolyse des cétals et les fragments du dérivé de fluoroboronbipyrrole obtenu par hydrolyse présentent une activité photosensible extrêmement élevée, tandis qu'un dérivé de géfitinib obtenu par hydrolyse peut être utilisé en tant qu'inhibiteur de la tyrosinase du récepteur du facteur de croissance épidermique (EGFR) pour inhiber la croissance tumorale. Les composés peuvent être préparés en médicaments anticancéreux à double efficacité thérapeutique photodynamique et chimiothérapeutique ciblant à la fois l'environnement faiblement acide extracellulaire tumoral et la tyrosine kinase EGFR.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2017/103190 WO2019056376A1 (fr) | 2017-09-25 | 2017-09-25 | Dérivé de géfitinib-fluoroboronbipyrrole sensible à l'acide, son procédé de préparation et son utilisation médicale |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2017/103190 WO2019056376A1 (fr) | 2017-09-25 | 2017-09-25 | Dérivé de géfitinib-fluoroboronbipyrrole sensible à l'acide, son procédé de préparation et son utilisation médicale |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2019056376A1 true WO2019056376A1 (fr) | 2019-03-28 |
Family
ID=65811000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2017/103190 WO2019056376A1 (fr) | 2017-09-25 | 2017-09-25 | Dérivé de géfitinib-fluoroboronbipyrrole sensible à l'acide, son procédé de préparation et son utilisation médicale |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2019056376A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021152505A1 (fr) | 2020-01-30 | 2021-08-05 | 3M Innovative Properties Company | Article et procédé pour traiter des caries dentaires interproximales |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104387412A (zh) * | 2014-12-17 | 2015-03-04 | 福州大学 | 埃罗替尼修饰的氟硼二吡咯衍生物及其制备和应用 |
| CN106565760A (zh) * | 2016-11-11 | 2017-04-19 | 深圳市声光动力生物医药科技有限公司 | 氟硼二吡咯衍生物及其制备方法和在医药上的应用 |
-
2017
- 2017-09-25 WO PCT/CN2017/103190 patent/WO2019056376A1/fr active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104387412A (zh) * | 2014-12-17 | 2015-03-04 | 福州大学 | 埃罗替尼修饰的氟硼二吡咯衍生物及其制备和应用 |
| CN106565760A (zh) * | 2016-11-11 | 2017-04-19 | 深圳市声光动力生物医药科技有限公司 | 氟硼二吡咯衍生物及其制备方法和在医药上的应用 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021152505A1 (fr) | 2020-01-30 | 2021-08-05 | 3M Innovative Properties Company | Article et procédé pour traiter des caries dentaires interproximales |
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