WO2016091167A1 - Dérivés de la quinoléine pour lutter contre le carcinome à cellules squameuses - Google Patents

Dérivés de la quinoléine pour lutter contre le carcinome à cellules squameuses Download PDF

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Publication number
WO2016091167A1
WO2016091167A1 PCT/CN2015/096776 CN2015096776W WO2016091167A1 WO 2016091167 A1 WO2016091167 A1 WO 2016091167A1 CN 2015096776 W CN2015096776 W CN 2015096776W WO 2016091167 A1 WO2016091167 A1 WO 2016091167A1
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WIPO (PCT)
Prior art keywords
compound
cell carcinoma
squamous cell
pharmaceutically acceptable
pharmaceutical composition
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PCT/CN2015/096776
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English (en)
Chinese (zh)
Inventor
王训强
缪亚东
周敏
王善春
杨玲
施伟
Original Assignee
正大天晴药业集团股份有限公司
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Priority to CN201580066234.9A priority Critical patent/CN106999485B/zh
Publication of WO2016091167A1 publication Critical patent/WO2016091167A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

  • This application belongs to the field of medical technology, and the present application relates to the use of quinoline derivatives for antitumor.
  • the present application relates to the use of a quinoline derivative for the treatment of lung squamous cell carcinoma.
  • Non-small cell lung cancer is one of the most common causes of cancer death, and the incidence is also high.
  • NSCLC non-small cell lung cancer
  • platinum-containing chemotherapy can improve patient survival, the prognosis of advanced non-small cell lung cancer remains extremely poor, with a 5-year survival rate of less than 10%. It has been reported that increasing the survival rate requires further studies on the tumorigenesis and chemical resistance machinery of lung cancer (Jemal A et al, Cancer Statistics, CA Cancer. J. Clin., 56, 106-130, 2006).
  • the main histological types of NSCLC include adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma.
  • adenocarcinoma and squamous cell carcinoma are the most common histological types of NSCLC. Compared with lung adenocarcinoma, the targeted treatment of lung squamous cell carcinoma has progressed significantly.
  • Targeted drugs for clinical efficacy of lung adenocarcinoma such as: epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), echinoderma microtubule-associated protein-4 (echinodern microtubule-associated protein-like 4, EML4)-anaplastic lymphoma kinase (ALK) fusion gene inhibitors, etc., have poor efficacy in lung squamous cell carcinoma (Yuan Hong et al, lung squamous cell carcinoma targeted therapy research Current Situation, Chinese Journal of Lung Cancer, 2013, Issue 10).
  • EGFR-TKI epidermal growth factor receptor-tyrosine kinase inhibitor
  • EML4 echinodern microtubule-associated protein-like 4, EML4-anaplastic lymphoma kinase
  • the 2014 NCCN guidelines recommend platinum or cisplatin/vinorelbine plus cetuximab as first-line treatment options for lung squamous cell carcinoma.
  • the cisplatin/gemcitabine regimen is superior to the cisplatin/pemetrexed regimen. Because lung squamous cell carcinoma has a very wide and complex genomic changes, there is no clear driver gene and targeted therapeutic drugs.
  • Three-generation platinum-containing dual-agent chemotherapy is still the standard treatment for advanced lung squamous cell carcinoma. Therefore, the development of effective drugs to treat lung squamous cell carcinoma is the key and hot spot of current research.
  • the application provides a method of treating lung squamous cell carcinoma, the method comprising administering to a patient in need of treatment a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof, having the structural formula below.
  • the application provides the use of Compound 1, or a pharmaceutically acceptable salt thereof, having the above formula, for the manufacture of a medicament for the treatment of lung squamous cell carcinoma.
  • the application provides a compound I or a pharmaceutical composition having the above formula, wherein the pharmaceutical composition comprises Compound 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable Carrier.
  • the application provides a method of treating lung squamous cell carcinoma, the method comprising administering to a patient in need of treatment a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof, having the structural formula below.
  • a method of treating advanced lung squamous cell carcinoma and/or metastatic lung squamous cell carcinoma comprising administering to a patient in need of treatment a therapeutically effective amount of Compound I or a pharmaceutically acceptable compound thereof Salt.
  • a method of treating EGFR mutated negative lung squamous cell carcinoma comprising administering to a patient in need of treatment a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof.
  • Compound I can be administered in the form of its free base or it can be administered in the form of its salts, hydrates and prodrugs which are converted in vivo to the free base form of Compound I.
  • a pharmaceutically acceptable salt of Compound I is within the scope of the present application and can be produced from different organic and inorganic acids by methods well known in the art.
  • the administration is in the form of Compound I hydrochloride. In some embodiments, the administration is in the form of Compound I monohydrochloride. In some embodiments, the administration is in the form of Compound I dihydrochloride. In some embodiments In the case of the crystal form of the compound I hydrochloride. In a particular embodiment, it is administered in the form of a crystal of Compound I dihydrochloride.
  • Compound 1, or a pharmaceutically acceptable salt thereof can be administered by a variety of routes including, but not limited to, those selected from the group consisting of oral, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, Intramuscular, rectal, buccal, intranasal, inhalation, vaginal, intraocular, topical, subcutaneous, intrahepatic, intra-articular, intraperitoneal, and intrathecal. In a particular embodiment, it is administered orally.
  • the amount of Compound I or a pharmaceutically acceptable salt thereof administered can be determined based on the severity of the disease, the response to the disease, any treatment-related toxicity, the age and health of the patient.
  • the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof is from 3 mg to 30 mg. In some embodiments, the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof, is from 5 mg to 20 mg. In some embodiments, the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof, is from 8 mg to 16 mg. In some embodiments, the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof, is from 10 mg to 14 mg. In a specific embodiment, the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof, is 8 mg. In a specific embodiment, the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof, is 10 mg. In a specific embodiment, the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof, is 12 mg.
  • Compound I or a pharmaceutically acceptable salt thereof can be administered one or more times a day. In some embodiments, Compound 1, or a pharmaceutically acceptable salt thereof, is administered once daily. In one embodiment, the oral solid preparation is administered once a day.
  • the method of administration can be comprehensively determined based on the activity, toxicity, and tolerance of the patient.
  • Compound 1, or a pharmaceutically acceptable salt thereof is administered in a separate manner.
  • the interval administration includes a administration period and a withdrawal period, and Compound I or a pharmaceutically acceptable salt thereof may be administered one or more times a day during the administration period.
  • Compound I or a pharmaceutically acceptable salt thereof is administered daily during the administration period, and then the administration is stopped for a certain period of time during the withdrawal period, followed by the administration period, and then the withdrawal period, which can be repeated a plurality of times.
  • the ratio of the administration period to the withdrawal period in days is 2:0.5 to 5, preferably 2:0.5 to 3, more preferably 2:0.5 to 2, still more preferably 2:0.5 to 1.
  • the continuous administration is discontinued for 2 weeks for 2 weeks. In some embodiments, administration once a day for 14 days, followed by 14 days of withdrawal; followed by 1 administration per day for 14 days, followed by 14 days of discontinuation, such continuous administration for 2 weeks
  • the two-week interval administration method can be repeated a plurality of times.
  • the continuous administration is discontinued for 2 weeks for 1 week. In some embodiments, administration once a day for 14 days, followed by 7 days of withdrawal; followed by 1 administration per day for 14 days, followed by 7 days of discontinuation, such continuous administration for 2 weeks
  • the interval of administration of the drug for one week can be repeated a plurality of times.
  • the administration is continued for 5 days for 2 days.
  • the drug is administered once a day for 5 days, then for 2 days; then once a day for 5 days, then for 2 days, such continuous administration for 5 days.
  • the two-day interval administration method can be repeated multiple times.
  • the oral administration is administered once daily at a dose of 12 mg, administered continuously for 2 weeks, and administered for 1 week.
  • the present application also provides the use of Compound 1, or a pharmaceutically acceptable salt thereof, of the formula: for the manufacture of a medicament for the treatment of lung squamous cell carcinoma.
  • Compound 1 for the manufacture of a medicament for the treatment of advanced lung squamous cell carcinoma and/or metastatic lung squamous cell carcinoma.
  • Compound I may be in its free base form, or it may be in the form of its salts, hydrates and prodrugs which are converted in vivo to the free base form of Compound I.
  • a pharmaceutically acceptable salt of Compound I is within the scope of the present application and can be produced from different organic and inorganic acids by methods well known in the art.
  • Compound 1, or a pharmaceutically acceptable salt thereof is the hydrochloride salt form of Compound I.
  • the amount of Compound I or a pharmaceutically acceptable salt thereof can be determined depending on the severity of the disease, the response of the disease, any treatment-related toxicity, the age of the patient, and the state of health.
  • Compound 1, or a pharmaceutically acceptable thereof is administered
  • the daily dose of the salt received is from 3 mg to 30 mg.
  • the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof is from 5 mg to 20 mg.
  • the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof is from 8 mg to 16 mg.
  • the daily dose of Compound 1, or a pharmaceutically acceptable salt thereof is from 10 mg to 14 mg.
  • the present application provides a compound I or a pharmaceutical composition having the following structural formula for treating lung squamous cell carcinoma, wherein the pharmaceutical composition comprises Compound 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable Acceptable carrier.
  • a Compound I or a pharmaceutical composition for treating advanced lung squamous cell carcinoma and/or metastatic lung squamous cell carcinoma wherein the pharmaceutical composition comprises Compound 1, or a pharmaceutically acceptable thereof a salt, and at least one pharmaceutically acceptable carrier.
  • a Compound I or a pharmaceutical composition for treating EGFR mutation-negative lung squamous cell carcinoma wherein the pharmaceutical composition comprises Compound 1, or a pharmaceutically acceptable salt thereof, and at least one A pharmaceutically acceptable carrier.
  • Compound I may be in its free base form, or it may be in the form of its salts, hydrates and prodrugs which are converted in vivo to the free base form of Compound I.
  • a pharmaceutically acceptable salt of Compound I is within the scope of the present application and can be produced from different organic and inorganic acids by methods well known in the art.
  • Compound 1, or a pharmaceutically acceptable salt thereof is the hydrochloride salt form of Compound I.
  • the amount of Compound I or a pharmaceutically acceptable salt thereof can be determined depending on the severity of the disease, the response of the disease, any treatment-related toxicity, the age of the patient, and the state of health.
  • the above pharmaceutical compositions contain from 3 mg to 30 mg of Compound 1, or a pharmaceutically acceptable salt thereof, on a unit dosage basis.
  • the above pharmaceutical compositions contain 5 mg to 20 mg of Compound 1, or a pharmaceutically acceptable salt thereof, on a unit dosage basis.
  • the above pharmaceutical compositions contain from 8 mg to 16 mg of Compound 1, or a pharmaceutically acceptable salt thereof, on a unit dosage basis.
  • the above pharmaceutical compositions contain 10 mg to 14 mg on a unit dosage basis.
  • Compound I or a pharmaceutically acceptable salt thereof in the present application, for example, for a tablet or a capsule, "containing 12 mg of Compound I on a unit dose basis" means that 12 mg of Compound I is contained per tablet or capsule per capsule.
  • the pharmaceutical composition contains 8, 10 or 12 mg of Compound 1, or a pharmaceutically acceptable salt thereof, on a unit dosage basis.
  • Compound I is formulated for oral, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal, buccal, intranasal, inhalation, vaginal, ocular Formulations for internal, topical, subcutaneous, intra-, intra-articular, intraperitoneal, and intrathecal administration; preferably suitable for oral administration, including tablets, capsules, powders, granules, pills, pastes, Powders and the like, preferably tablets and capsules.
  • the tablet may be a common tablet, a dispersible tablet, an effervescent tablet, a sustained release tablet, a controlled release tablet or an enteric coated tablet
  • the capsule may be a general capsule, a sustained release capsule, a controlled release capsule or an enteric coated capsule.
  • pharmaceutically acceptable carriers include fillers, absorbents, wetting agents, binders, disintegrants, lubricants, and the like.
  • Filling agents include starch, lactose, mannitol, microcrystalline cellulose, etc.; absorbents include calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; wetting agents include water, ethanol, etc.; binders include hypromellose, poly Retardone, microcrystalline cellulose, etc.; disintegrants include croscarmellose sodium, crospovidone, surfactant, low-substituted hydroxypropyl cellulose, etc.; lubricants include magnesium stearate, talc Powder, polyethylene glycol, sodium lauryl sulfate, micronized silica gel, talcum powder, and the like. Pharmaceutical excipients also include coloring agents, sweeteners, and the like.
  • the pharmaceutical composition may be suitable for oral, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal, buccal, intranasal, inhalation, vaginal, intraocular, meridian Formulations for topical administration, subcutaneous, intra-, intra-articular, intraperitoneal and intrathecal administration; preferably suitable for oral administration, including tablets, capsules, powders, granules, dropping pills, pastes, powders, etc. Preference is given to tablets and capsules.
  • the tablet may be a common tablet, a dispersible tablet, an effervescent tablet, a sustained release tablet, a controlled release tablet or an enteric coated tablet
  • the capsule may be a general capsule, a sustained release capsule, a controlled release capsule or an enteric coated capsule.
  • pharmaceutically acceptable carriers include fillers, absorbents, wetting agents, binders, disintegrants, lubricants, and the like.
  • Filling agents include starch, lactose, mannitol, microcrystalline cellulose, etc.; absorbents include calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; wetting agents include water, ethanol, etc.; binders include hypromellose, poly Retardone, microcrystalline cellulose, etc.; disintegrants include croscarmellose sodium, crospovidone, surfactant, low-substituted hydroxypropyl cellulose, etc.; lubricants include magnesium stearate, talc Powder, polyethylene glycol, sodium lauryl sulfate, micronized silica gel, talcum powder, and the like. Pharmaceutical excipients also include coloring agents, sweeteners, and the like.
  • Compound I or the above pharmaceutical composition is administered in a separate manner.
  • the interval administration includes a administration period and a withdrawal period, and the compound I or the above pharmaceutical composition may be administered one or more times a day during the administration period.
  • Compound I or the above-mentioned pharmaceutical composition is administered daily during the administration period, and then the administration is stopped for a certain period of time during the withdrawal period, followed by the administration period, and then the withdrawal period, which can be repeated a plurality of times.
  • the ratio of the number of days in the administration period and the withdrawal period is 2: 0.5 to 5, It is preferably 2: 0.5 to 3, more preferably 2: 0.5 to 2, still more preferably 2: 0.5 to 1.
  • the continuous administration is discontinued for 2 weeks for 2 weeks. In some embodiments, administration once a day for 14 days, followed by 14 days of withdrawal; followed by 1 administration per day for 14 days, followed by 14 days of discontinuation, such continuous administration for 2 weeks
  • the two-week interval administration method can be repeated a plurality of times.
  • the continuous administration is discontinued for 2 weeks for 1 week. In some embodiments, administration once a day for 14 days, followed by 7 days of withdrawal; followed by 1 administration per day for 14 days, followed by 7 days of discontinuation, such continuous administration for 2 weeks
  • the interval of administration of the drug for one week can be repeated a plurality of times.
  • the administration is continued for 5 days for 2 days.
  • the drug is administered once a day for 5 days, then for 2 days; then once a day for 5 days, then for 2 days, such continuous administration for 5 days.
  • the two-day interval administration method can be repeated multiple times.
  • Compound I or the above pharmaceutical composition can be administered one or more times a day. In some embodiments, Compound I or a pharmaceutical composition described above is administered once a day. In one embodiment, the oral solid preparation is administered once a day.
  • the oral administration is administered once daily at a dose of 12 mg, administered continuously for 2 weeks, and administered for 1 week.
  • the amount of Compound I administered can be determined based on the severity of the disease, the response to the disease, any treatment-related toxicity, the age of the patient, and the state of health.
  • the period of administration can be comprehensively determined based on the activity, toxicity, and tolerance of the patient.
  • the advanced lung squamous cell carcinoma is a stage IIIB-IV lung squamous cell carcinoma.
  • EGFR epidermal growth factor receptor
  • negative mutation of EGFR generally means that the EGFR gene mutation is not detected by a gene detection method commonly used in clinical diagnosis.
  • the EGFR mutation status can be detected by a variety of methods.
  • DNA mutation detection is the preferred method for detecting EGFR status.
  • Multiple DNA mutation detection assays can be used to detect EGFR mutation status in tumor cells.
  • the most common EGFR mutation in non-small cell lung cancer patients is Direct exon 19 deletion and exon 21 mutation, direct DNA sequencing of exon 18-21 (or exons 19 and 21 only) is a reasonable choice.
  • Patient means a mammal, preferably a human.
  • “Pharmaceutically acceptable” means that it is used in the preparation of a pharmaceutical composition which is generally safe, non-toxic and neither biologically or otherwise undesirable, and which includes its use for human pharmaceutical use. Accepted.
  • “Pharmaceutically acceptable salt” includes, but is not limited to, acid addition salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or with organic acids such as acetic acid, trifluoroacetic acid, propionic acid , caproic acid, heptanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, Mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, 3-phenyl
  • terapéuticaally effective amount is meant an amount of a compound that is sufficient to effect control of the disease when administered to a human for the treatment of a disease.
  • Treatment means any administration of a therapeutically effective amount of a compound and includes:
  • progression-free survival P50 refers to the time when disease progression occurs in 50% of patients participating in the statistics
  • mean progression-free survival refers to the mean value of progression-free survival of patients participating in the outcome statistics.
  • Example 2 contains 1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl a capsule of cyclopropylamine dihydrochloride (dihydrochloride salt of Compound I)
  • the dihydrochloride salt of Compound I is pulverized and passed through a 80 mesh sieve; then uniformly mixed with mannitol and hydroxypropylcellulose; then a prescribed amount of microcrystalline cellulose is added, uniformly mixed, and passed through a 0.8 mm sieve; The magnesium stearate is mixed evenly and filled with capsules.
  • PR partial remission
  • GP General remission
  • Cisplatin Cisplatin
  • D Docetaxel
  • the specific effect is unknown.
  • Compound I dihydrochloride capsules were administered once daily at a dose of 12 mg (continuously with 1 week for 1 week for one treatment cycle) starting on September 28, 2013.
  • the long diameter of the left upper lobe lesion was slightly reduced at the end of the second cycle, with a value of 86 mm.
  • the disease persisted for 10 cycles and the tumor response was good.
  • the lesion of the left upper lobe was reduced, the longest diameter was 81 mm, and the lesion showed obvious cavity necrosis.
  • Cisplatin and gemcitabine were given from March 26, 2013 to June 5, 2013. The best effect was SD for 4 cycles of chemotherapy. After the above chemotherapy, the local radiotherapy was performed for one cycle, and the adverse reactions were mild. Two cycles of chemotherapy with cisplatin and gemcitabine were given from September 9, 2013 to October 6, 2013. The CT was reviewed in December 2013, suggesting that the disease progressed. On March 24, 2014, a dose of docetaxel chemotherapy was given. After chemotherapy, bone marrow suppression, oral infection, and pneumonia occurred, and the symptomatic treatment improved. On December 10, 2014, the CT examination revealed: 1. The soft tissue shadow of the right upper hilar was increased earlier; 2. The multiple lungs of the lungs were less changed than before; 3.
  • a capsule of 12 mg of Compound I dihydrochloride was orally administered once a day (continuous administration for 1 week for 1 week for one treatment cycle).
  • the patient received treatment for 1 cycle, and enhanced CT showed a soft tissue density tumor of the right hilar, which was slightly smaller than the previous one; the left clavicle, mediastinum, and right hilar multiple lymph nodes; lung inflammation, the range was changed before Large, double lung multiple lung vesicles, less change than before; according to RECIST1.1 evaluation of SD (small), the total target lesion is 66, 10mm smaller than the baseline.
  • the patient's enhanced CT showed a soft tissue density tumor of the right hilar, which was slightly smaller than before.
  • the total target lesion was 63mm; on September 8, 2015, enhanced CT showed that the lesion was further reduced, and the total target lesion was 57mm.
  • enhanced CT showed that the lesion was reduced, which was not changed much before, and the total target lesion was 56mm.
  • the patient's adverse reactions are basically tolerable and continue to be treated.

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  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention a pour objet des dérivés de la quinoléine pour lutter contre le carcinome à cellules squameuses. Fait l'objet de cette invention une 1-[[[4-(4-fluor-2-méthyl-1H-indole-5-yl)oxygène-6-méthoxy quinoline-7-yl]radical d'oxygène]méthyl]cyclopropylamine ou son sel pharmaceutiquement acceptable pour lutter contre lutter contre le carcinome à cellules squameuses et correspond à un placebo visant à améliorer la résistance des malades souffrant d'un lutter contre le carcinome à cellules squameuses.
PCT/CN2015/096776 2014-12-09 2015-12-09 Dérivés de la quinoléine pour lutter contre le carcinome à cellules squameuses WO2016091167A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201580066234.9A CN106999485B (zh) 2014-12-09 2015-12-09 抗肺鳞癌的喹啉衍生物

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CN201410748467 2014-12-09
CN201410748467.4 2014-12-09

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020057536A1 (fr) * 2018-09-18 2020-03-26 正大天晴药业集团股份有限公司 Dérivé de quinoléine pour le traitement d'une tumeur cérébrale

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005073224A2 (fr) * 2004-01-23 2005-08-11 Amgen Inc Composes et methodes d'utilisation de ces derniers
CN101809012A (zh) * 2007-03-14 2010-08-18 南京爱德程医药科技有限公司 作为血管生成抑制剂的螺取代化合物
CN102344438A (zh) * 2010-08-01 2012-02-08 江苏正大天晴药业股份有限公司 喹啉衍生物的结晶及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005073224A2 (fr) * 2004-01-23 2005-08-11 Amgen Inc Composes et methodes d'utilisation de ces derniers
CN101809012A (zh) * 2007-03-14 2010-08-18 南京爱德程医药科技有限公司 作为血管生成抑制剂的螺取代化合物
CN102344438A (zh) * 2010-08-01 2012-02-08 江苏正大天晴药业股份有限公司 喹啉衍生物的结晶及其制备方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020057536A1 (fr) * 2018-09-18 2020-03-26 正大天晴药业集团股份有限公司 Dérivé de quinoléine pour le traitement d'une tumeur cérébrale

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