JP5794873B2 - 抗腫瘍剤 - Google Patents
抗腫瘍剤 Download PDFInfo
- Publication number
- JP5794873B2 JP5794873B2 JP2011206481A JP2011206481A JP5794873B2 JP 5794873 B2 JP5794873 B2 JP 5794873B2 JP 2011206481 A JP2011206481 A JP 2011206481A JP 2011206481 A JP2011206481 A JP 2011206481A JP 5794873 B2 JP5794873 B2 JP 5794873B2
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- Prior art keywords
- cancer
- acid
- everolimus
- formula
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Images
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
[式中、R1はC1−6アルキル基またはC3−8シクロアルキル基を意味する。R2は水素原子またはC1−6アルコキシ基を意味する。R3は水素原子またはハロゲン原子を意味する。]
および式(II)で表されるエベロリムス
を併用する抗腫瘍剤。
[2] 上記式(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上記式(II)で表されるエベロリムスを同時にまたは別々に投与する抗腫瘍剤。
[3] 上記式(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上記式(II)で表されるエベロリムスを含む抗腫瘍剤。
[4] 上記式(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と併用することによる腫瘍治療のための上記式(II)で表されるエベロリムス。
[5] 上記式(II)で表されるエベロリムスと併用することによる腫瘍治療のための上記式(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。
[6] 上記式(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上記式(II)で表されるエベロリムスを併用する腫瘍の治療方法。
[7] 上記式(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、上記式(II)で表されるエベロリムスおよび賦形剤を含む医薬組成物。
[8] 上記式(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医薬組成物と上記式(II)で表されるエベロリムスおよび賦形剤を含む医薬組成物とを含むキット。
4−[3−クロロ−4−(シクロプロピルアミノカルボニル)アミノフェノキシ]−7−メトキシ−6−キノリンカルボキサミド
4−[3−クロロ−4−(メチルアミノカルボニル)アミノフェノキシ]−7−メトキシ−6−キノリンカルボキサミド
4−[3−クロロ−4−(エチルアミノカルボニル)アミノフェノキシ]−7−メトキシ−6−キノリンカルボキサミド
N6−メトキシ−4−(3−クロロ−4−{[(シクロプロピルアミノ)カルボニル)アミノ]フェノキシ}−7−メトキシ−6−キノリンカルボキサミド
および
N6−メトキシ−4−(3−クロロ−4−{[(エチルアミノ)カルボニル]アミノ}フェノキシ)−7−メトキシ−6−キノリンカルボキサミド
からなる群から選択される1種以上の化合物であり、
より好ましくは、
4−[3−クロロ−4−(シクロプロピルアミノカルボニル)アミノフェノキシ]−7−メトキシ−6−キノリンカルボキシアミド
である(以下、化合物Aと表記することがある)。
実施例1 ヒト腎細胞癌細胞株(Caki−1)に対する化合物Aとエベロリムスの併用による腫瘍増殖阻害作用
各群5例のヌードマウス(CAnN.Cg−Foxn1nu/CrlCrlj、雌、日本チャールズリバー株式会社)を使用して、化合物A、エベロリムスまたは両化合物を投与した場合の抗腫瘍効果を評価した。ヒト由来の腎細胞癌の細胞株Caki−1(ATCC)を、培地(RPMI−1640、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。その混和液を各マウスの左脇腹皮下部に、0.1mLずつ移植した。
移植から48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=長径(mm)×短径(mm)×短径(mm)/2
各群のマウスに、化合物A溶液および溶媒、エベロリムス懸濁液および精製水、または、化合物A溶液およびエベロリムス懸濁液を、各10mL/kgずつ、1日1回、15日間、経口投与した。化合物Aおよびエベロリムスの投与用量は、それぞれ10mg/kgおよび30mg/kgとした。なお、対照群には、各10mL/kgの精製水および溶媒を投与した。
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