JP6858132B2 - 乳がん治療剤 - Google Patents
乳がん治療剤 Download PDFInfo
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- JP6858132B2 JP6858132B2 JP2017556119A JP2017556119A JP6858132B2 JP 6858132 B2 JP6858132 B2 JP 6858132B2 JP 2017556119 A JP2017556119 A JP 2017556119A JP 2017556119 A JP2017556119 A JP 2017556119A JP 6858132 B2 JP6858132 B2 JP 6858132B2
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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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
[1] 式(I)で表される化合物またはその薬理学的に許容される塩を含む乳がん治療剤。
[3] 乳がん治療のための式(I)で表される化合物またはその薬理学的に許容される塩。
[4] 式(I)で表される化合物またはその薬理学的に許容される塩をそれを必要とする患者に投与する乳がんの治療方法。
[5] 式(I)で表される化合物またはその薬理学的に許容される塩を含む乳がん治療用組成物。
[6] 式(I)で表される化合物またはその薬理学的に許容される塩および賦形剤を含む乳がん治療用組成物。
[7] 乳がんが局所進行乳がん、転移乳がんまたは再発乳がんである上記治療剤、使用、化合物、方法または組成物。
[8] 乳がんがFGFRを発現しているものである上記治療剤、使用、化合物、方法または組成物。
[9] FGFRがFGFR1、FGFR2またはFGFR3である上記治療剤、使用、化合物、方法または組成物。
5−((2−(4−(1−(2−ヒドロキシエチル)ピペリジン−4−イル)ベンズアミド)ピリジン−4−イル)オキシ)−6−(2−メトキシエトキシ)−N−メチル−1H−インドール−1−カルボキサミド 1.5コハク酸塩(以下、化合物Aと表記する場合がある)の製造
1H-NMR Spectrum (600MHz, CD3OD) δ(ppm): 1.96-2.10 (4H, m), 2.52 (6H, s), 2.93 (1H, m), 2.96 (3H, s), 3.01 (2H, m), 3.16 (2H, t, J=5.4 Hz), 3.22 (3H, s), 3.56 (2H, t, J=4.7 Hz), 3.61 (2H, m), 3.87 (2H, t, J=5.4 Hz), 4.14 (2H, t, J=4.6 Hz), 6.61 (1H, d, J=3.6 Hz), 6.68 (1H, dd, J=5.8, 2.3 Hz), 7.37 (1H, s), 7.42 (2H, d, J=8.3 Hz), 7.58 (1H, d, J=3.6 Hz), 7.73 (1H, d, J=2.2 Hz), 7.88 (2H, d, J=8.3 Hz), 8.08 (1H, s), 8.15 (1H, d, J=5.8 Hz).
13C-NMR Spectrum (100MHz, solid state) δ(ppm): 27.1, 28.3, 29.7, 34.8, 38.0, 41.3, 54.0, 57.3, 59.7, 60.9, 72.1, 72.5, 103.3, 104.2, 108.5, 116.9, 126.9, 128.6, 134.5, 136.7, 140.7, 149.4, 151.3, 155.1, 169.5, 170.1, 175.6, 179.9, 183.7.
各群4例のヌードマウス(BALB/cAJcl−nu/nu、雌、日本クレア株式会社)を使用して、化合物Aを投与した場合の抗腫瘍効果を評価した。
ヒト由来乳癌細胞株MFM223(ECACC)について、予め馴化処理を行った。MFM223細胞を、HBSS(和光純薬工業株式会社)に、2×108個/mLの濃度となるように懸濁した。当該懸濁液に、同容量のマトリゲルTMマトリックス(日本ベクトン・ディッキンソン株式会社)を添加し、十分に混和した。その混和液をヌードマウス(CAnN.Cg−Foxn1nu/CrlCrlj、雌、日本チャールズリバー株式会社)の右脇腹皮下部に、0.1mLずつ移植した。飼育中は終濃度2.5μg/mLに調製したβ―エストラジオール(和光純薬工業株式会社)を飲水投与させた。移植後46日に、形成した腫瘍を摘出し、細かく裁断し、終濃度380unit/mL Type I collagenase(SIGMA)および終濃度160Kunit/mL Deoxyribonuclease I(SIGMA)を含むHBSSを加え、37℃にて攪拌した。100μm セルストレイナー(Falcon(登録商標))を通した後、遠心し細胞を回収し、10%ウシ血清を含んだEMEM培地(和光純薬工業株式会社)にて培養した。
移植から20日後に、腫瘍の長径および短径を電子デジタルノギス(デジマチックTMキャリパ、株式会社ミツトヨ)で測定した。各群の腫瘍体積の平均値がほぼ等しくなるように、マウスの群分けを行った。なお、腫瘍の体積は、以下の式に従って算出した。
腫瘍体積(mm3)=長径(mm)×短径(mm)×短径(mm)/2
各群のマウスに、12.5mg/kgまたは50mg/kg、20mL/kgの投与容量で1日1回、12日間、経口投与した。なお、対照群には、20mL/kgの精製水を投与した。
Claims (6)
- 塩が1.5コハク酸塩である、請求項1に記載の治療剤。
- 5−((2−(4−(1−(2−ヒドロキシエチル)ピペリジン−4−イル)ベンズアミド)ピリジン−4−イル)オキシ)−6−(2−メトキシエトキシ)−N−メチル−1H−インドール−1−カルボキサミドまたはその薬理学的に許容される塩を含む、乳がん治療用医薬組成物。
- 塩が1.5コハク酸塩である、請求項3に記載の医薬組成物。
- 乳がんが局所進行乳がん、転移乳がんまたは再発乳がんである、請求項1または2に記載の治療剤。
- 乳がんが局所進行乳がん、転移乳がんまたは再発乳がんである、請求項3または4に記載の医薬組成物。
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PCT/JP2016/087349 WO2017104739A1 (ja) | 2015-12-17 | 2016-12-15 | 乳がん治療剤 |
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MX2020008610A (es) | 2018-03-28 | 2020-09-21 | Eisai R&D Man Co Ltd | Agente terapeutico para carcinoma hepatocelular. |
BR112022020786A2 (pt) * | 2020-04-17 | 2022-11-29 | Eisai R&D Man Co Ltd | Agente terapêutico de câncer de mama |
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CA3001969A1 (en) | 2017-06-22 |
CN115177619A (zh) | 2022-10-14 |
KR20180094862A (ko) | 2018-08-24 |
CN108367000A (zh) | 2018-08-03 |
JPWO2017104739A1 (ja) | 2018-10-04 |
SG10201913213WA (en) | 2020-03-30 |
KR102486722B1 (ko) | 2023-01-11 |
AU2016374441B2 (en) | 2021-10-21 |
RU2730503C2 (ru) | 2020-08-24 |
RU2018119102A3 (ja) | 2020-02-04 |
RU2018119102A (ru) | 2020-01-17 |
WO2017104739A1 (ja) | 2017-06-22 |
IL258671A (en) | 2018-06-28 |
EP3391885B1 (en) | 2021-03-17 |
CA3001969C (en) | 2023-10-03 |
SG11201803118WA (en) | 2018-05-30 |
EP3391885A1 (en) | 2018-10-24 |
ES2867804T3 (es) | 2021-10-20 |
US20180303817A1 (en) | 2018-10-25 |
AU2016374441A1 (en) | 2018-05-10 |
BR112018010103A2 (ja) | 2018-11-21 |
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