JP2023532027A - 新規な化合物およびこれを含む耐性がんの予防または治療用薬学組成物 - Google Patents
新規な化合物およびこれを含む耐性がんの予防または治療用薬学組成物 Download PDFInfo
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Images
Classifications
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
Abstract
Description
本出願は、新規な化合物およびこれを含むがんの予防または治療用薬学組成物に関する。
その他にも、PI3K/AKT、MAPK、JAK2/STAT3シグナル機序(signaling pathway)と関連すると知られている。
また、本出願の他の一態様は、新規な化合物を含むがんの予防または治療用薬学組成物を提供することにある。
また、本出願の他の一態様は、新規な化合物を含む耐性がんの予防または治療用薬学組成物を提供することにある。
また、本出願の他の一態様は、新規な化合物の耐性がんの予防または治療用途を提供することにある。
また、本出願の他の一態様は、新規な化合物を耐性がんを有する個体に投与して、腫瘍学的療法に対して耐性を示すがんを治療する方法を提供することにある。
本出願の解決課題は、以上で言及されたものに限定されず、言及されていない他の解決課題は、下記の記載から当業者が明確に理解できる。
L1は、直接連結されるか、C1-10のアルキレンであり;
前記R1およびR2は、5員~12員のモノサイクリックまたはビサイクリック環を形成しつつ連結されてもよい。
本出願の一実施例において、前記組成物は、薬学的に許容可能な担体、賦形剤、希釈剤または免疫補助剤をさらに含んでもよい。
本出願の一実施例において、前記組成物は、SERCAタンパク質発現を抑制することができる。
本出願の一実施例において、前記耐性がんは、抗がん薬物に対する耐性を有するか、放射能に対する耐性を有することができる。
本出願の一実施例による化合物またはその薬学的に許容可能な塩を含む組成物は、抗がん剤または放射線に対する耐性を有するがんの耐性を克服し、効果的に耐性がんを治療することができる。
本出願の一実施例による化合物またはその薬学的に許容可能な塩を含む組成物は、単独使用の場合にも、がんの予防または治療効果がある。
本出願による効果は、上記に例示された内容によって限定されず、さらに多様な効果が本明細書内に含まれている。
本出願の一実施例は、下記化学式1で表される化合物またはその薬学的に許容可能な塩を提供する。
Zbは、それぞれ独立して、フェニル、ベンジル、C1-6アルキル、C4-8ヘテロシクロアルキル、またはC3-8シクロアルキルであり、前記フェニル、ベンジル、C1-6アルキル、C4-8ヘテロシクロアルキルまたはC3-8シクロアルキルは、ハロゲン、-OH、-S(=O)2Zb、-OC2-6アルキルOZa、C1-6アルキル、C1-6ハロアルキル、-OC1-4アルキル、-NH2、-CN、または-NZaZaから独立して選択された0個~3個の置換基により置換され;
Zcは、それぞれ独立して、水素、またはC1-6アルキルであるか、グループCZcZcは、C3-8シクロアルキル環を形成することができる。
C1-6直鎖または分岐鎖アルキル、
L1は、直接連結されるか、C1-10のアルキレンであってもよい。具体的には、C1-6のアルキレンであってもよく、より具体的には、C1-3のアルキレンであってもよい。
前記mおよびyは、それぞれ独立して、0~2の整数でありうる。具体的には、前記mは、1であり、前記yは、1または2でありうる。
「アルキルアミノ」または「アリールアミノ」という用語は、それぞれ1つまたは2つのアルキルまたはアリール置換体を有するアミノ基を意味する。
本明細書において使用されるような「ハロ」という用語は、クロロ、ブロモ、ヨードおよびフルオロを含む。
本願において使用されるような表現「薬学的に許容可能な塩」は、薬学的に許容可能な本出願の化合物の有機または無機塩をいう。
本出願による化合物は、下記化学式からなる群から選ばれた少なくとも1つの化合物でありうるが、これに限定されない。
また、本出願は、耐性がんの治療に使用するための化学式1で表される化合物またはその薬学的に許容可能な塩の用途を提供する。
耐性がん、化学式1で表される化合物またはその薬学的に許容可能な塩は、前述した内容と同一で、具体的な説明は、省略する。
用語「投与」は、適切な方法で個体に所定の物質を導入することを意味する。
耐性がん、化学式1で表される化合物またはその薬学的に許容可能な塩は、前述した内容と同一で、具体的な説明は、省略する。
耐性がんを有する対象は、ヒト、ウシ、イヌ、ギニア、ピッグ、ウサギ、ニワトリまたは昆虫などを含んでもよい。
耐性がん、耐性がんを有する対象、化学式1で表される化合物またはその薬学的に許容可能な塩は、前述した内容と同一で、具体的な説明は、省略する。
下記製造例の方法で本出願による化合物を製造した。
1.製造例1:tetrahydro-2H-pyrazino[1,2-a]pyrazine-1,4(3H,6H)-dione
1)段階1:1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid
MS (ESI) m/z for C7H11N3O2 [M+H]+ : calcd 170.0930, found 170.0917.
MS (ESI) m/z for C18H19N3O2[M+H]+:calcd310.1556,found310.1550.
製造例2で収得した化合物(化学式N501)を出発物質として使用して下記反応式6の段階を追加にさらに進めて、化学式N513の化合物を収得した。
MS (ESI) m/z for C25H25N3O2[M+H]+:calcd400.2025,found400.2018.
4.製造例4:化学式S461
Mass 260.13
製造例4で収得した化合物(化学式S461)を出発物質として使用して下記反応式8の段階を追加にさらに進めて、化学式S462の化合物を収得した。
Mass 350.18
Mass 266.09
製造例6で収得した化合物(化学式S471)を出発物質として使用して下記反応式8の段階を追加にさらに進めて、化学式S472の化合物を収得した。
Mass 356.14
Mass 377.19
Mass 439.21
Mass 377.06
Mass 329.16
Mass 389.19
Mass 345.11
Mass 359.2
Mass 311.14
Mass 311.2
Mass 311.2
Mass 336.17
Mass 451.2
Mass 451.2
Mass 451.2
Mass 401.2
Mass 452.2
Mass 402.2
Mass 402.2
Mass 311.2
製造例26の化学式N401の化合物を用いて下記化学式N411の化合物を製造した。
Mass 451.21
製造例26の化学式N401の化合物を用いて下記化学式N412の化合物を製造した。
Mass 451.21
製造例26の化学式N401の化合物を用いて下記化学式N413の化合物を製造した。
Mass 401.19
製造例26の化学式N401の化合物を用いて下記化学式N414の化合物を製造した。
Mass 477.22
製造例26の化学式N401の化合物を用いて下記化学式N422の化合物を製造した。
Mass 452.2
製造例26の化学式N401の化合物を用いて下記化学式N423の化合物を製造した。
Mass 402.19
Mass 402.19
製造例2のN501化合物を用いて下記N502化合物を製造した。
Mass 400.2
製造例34のN502化合物を出発物質として用いて下記反応をさらに進めて、N503化合物を製造した。
Mass 490.24
製造例2のN501化合物を用いて下記N504化合物を製造した。
Mass 496.29
製造例2のN501化合物を用いて下記N511化合物を製造した。
Mass 450.21
製造例2のN501化合物を用いて下記N512化合物を製造した。
Mass 450.21
製造例2のN501化合物を用いて下記N514化合物を製造した。
Mass 476.23
Mass 451.4
Mass 401.2
Mass 401.2
Mass 310.15
Mass 450.21
Mass 450.21
Mass 400.2
Mass 476.23
Mass 451.21
Mass 484.4
Mass 336.2
製造例50で収得した化学式N701の化合物を出発物質として使用して下記反応式30の段階をさらに進めて、化学式N711の化合物を収得した。
Mass 476.4
製造例50で収得した化学式N701の化合物を出発物質として使用して下記反応式31の段階をさらに進めて、化学式N712の化合物を収得した。
Mass 476.23
製造例50で収得した化学式N701の化合物を出発物質として使用して下記反応式32の段階をさらに進めて、化学式N713の化合物を収得した。
Mass 426.21
製造例50で収得した化学式N701の化合物を出発物質として使用して下記反応式33の段階をさらに進めて、化学式N714の化合物を収得した。
Mass 502.4
製造例50で収得した化学式N701の化合物を出発物質として使用して下記反応式34の段階をさらに進めて、化学式N722の化合物を収得した。
Mass 477.4
製造例50で収得した化学式N701の化合物を出発物質として使用して下記反応式35の段階をさらに進めて、化学式N723の化合物を収得した。
Mass 427.2
製造例50で収得した化学式N701の化合物を出発物質として使用して下記反応式36の段階をさらに進めて、化学式N724の化合物を収得した。
Mass 427.2
Mass 360.17
Mass 500.23
Mass 500.4
Mass 450.2
Mass 526.4
Mass 524.4
製造例63の反応式42で収得した化合物を出発物質として使用して下記反応式44の段階をさらに進めて、化学式S2140の化合物を収得した。
Mass 524.23
製造例63の反応式42で収得した化合物を出発物質として使用して下記反応式45の段階をさらに進めて、化学式S2141の化合物を収得した。
Mass 474.4
製造例63の反応式42で収得した化合物を出発物質として使用して下記反応式46の段階をさらに進めて、化学式S2142の化合物を収得した。
Mass 550.4
Mass 350.2
製造例67の反応式47で収得した化合物S2217を出発物質として使用して下記反応式48の段階をさらに進めて、化学式S2126の化合物を収得した。
Mass 490.4
製造例67の反応式47で収得した化合物S2217を出発物質として使用して下記反応式49の段階をさらに進めて、化学式S2127の化合物を収得した。
Mass 490.4
製造例67の反応式47で収得した化合物S2217を出発物質として使用して下記反応式50の段階をさらに進めて、化学式S2130の化合物を収得した。
Mass 440.2
製造例67の反応式47で収得した化合物S2217を出発物質として使用して下記反応式51の段階をさらに進めて、化学式S2131の化合物を収得した。
Mass 516.4
Mass 338.18
Mass 324.17
Mass 338.18
Mass 366.21
Mass 350.18
Mass 366.21
Mass 394.24
Mass 400.2
製造例の化合物の抗がん治療活性増進効果
1.SKOV3とSKOV3-TRの準備
細胞増殖や生存を測定するWST-1分析結果によれば、パクリタキセル処理によってSKOV3およびSKOV3-TRで物質代謝の減少を誘発した。SKOV3の79とSKOV3-TRの79種に対してパクリタキセル(Paclitaxel)と併用処理した後、WST-1分析を実施した。
細胞増殖や生存を測定するWST-1分析結果によれば、ドセタキセル処理によってSKOV3およびSKOV3-TR物質代謝の減少を誘発した。
SKOV3の79種とSKOV3-TRの79種に対してドセタキセルと併用処理した後、WST-1分析を実施した。
Claims (17)
- 下記化学式1:
L1は、直接連結されるか、C1-10のアルキレンであり;
Ar1は、C1-12アルキルまたはO、NまたはSから独立して選択される0個~3個のヘテロ原子を含有できる5員~16員のモノサイクリック、ビサイクリック、トリサイクリック、またはテトラサイクリック環であり、これらは、置換されないか、C1-6ハロアルキル、ハロゲン、オキソ、-OCHF2、-CN、ニトロ、-C(=O)NZaZa、-C(=O)Zb、-C(=O)OZb、-C(=NZa)NZaZa、-OZa、-OC(=O)Zb、-OC(=O)NZaZa、-O-C1-6アルキルN(Za)C(=O)OZb、-OC(=O)N(Za)S(=O)2Zb、-OC2-6アルキルNZaZa、-OC2-6アルキルOZa、-SZa、-S(=O)Zb、-S(=O)2Zb、-S(=O)2NZaZa、-S(=O)2N(Za)C(=O)Zb、-S(=O)2N(Za)C(=O)OZb、-S(=O)2N(Za)C(=O)NZaZa、-NZaZa、-NZcZc、-N(Za)C(=O)Zb、-N(Za)C(=O)OZb、-N(Za)C(=O)NZaZa、-N(Za)C(=NZa)NZaZa、-N(Za)S(=O)2Zb、-N(Za)S(=O)2NZaZa、-NZaC2-6アルキルNZaZa、-NZaC2-6アルキルOZa、C6-10アリール、C5-10ヘテロアリール、-C1-6アルキル、-C3-10シクロアルキル、-C2-6アルケニルまたは-C2-6アルキニル(ここで、-C1-6アルキル、-C3-10シクロアルキル、-C2-6アルケニルまたは-C2-6アルキニルは、C1-6ハロアルキル、ハロゲン、シアノ、ニトロ、C6-12アリール、またはC5-12ヘテロアリールから独立して選択される0個~3個の置換基により置換される)から独立して選択されるグループで置換されてもよく;
Zaは、それぞれ独立して、水素またはZbであり;
Zbは、それぞれ独立して、フェニル、ベンジル、C1-6アルキル、C4-8ヘテロシクロアルキル、またはC3-8シクロアルキルであり、前記フェニル、ベンジル、C1-6アルキル、C4-8ヘテロシクロアルキルまたはC3-8シクロアルキルは、ハロゲン、-OH、-S(=O)2Zb、-OC2-6アルキルOZa、C1-6アルキル、C1-6ハロアルキル、-OC1-4アルキル、-NH2、-CN、または-NZaZaから独立して選択される0個~3個の置換基により置換され;
Zcは、それぞれ独立して、水素、またはC1-6アルキルであるか、グループCZcZcは、C3-8シクロアルキル環を形成することができ;
mおよびyは、それぞれ独立して、0~2の整数であり、
R1またはR2は、それぞれ独立して、水素、C1-6アルキル、C1-6アルコキシ、C1-6アルコキシカルボニル、ハロC1-6アルキル、C2-6アルケニル、C4-15のモノサイクリックまたはビサイクリック環(これは、C3-10シクロアルキル;C6-12アリール;N、OおよびSから独立して選択される、0個~3個のヘテロ原子を含有する、5員または6員の飽和または部分的飽和のヘテロ環;N、OおよびSから独立して選択される、0個~3個のヘテロ原子(前記ヘテロ原子のうち2個以上がOまたはSであるわけではない)を含有する5員または6員の芳香族ヘテロ環;またはN、OおよびSから独立して選択される、0個~3個のヘテロ原子を含有する、7員~15員の飽和、部分的飽和、または不飽和のヘテロ環)であり;
前記R1およびR2は、5員~12員のモノサイクリックまたはビサイクリック環を形成しつつ連結され得る)
で表される
ことを特徴とする化合物またはその薬学的に許容可能な塩。 - 前記化学式1で表される化合物は、
下記化学式2~10:
L1は、直接連結されるか、C1-6のアルキレンであり;
A1、A2、A3、またはA4は、それぞれ独立して、CRまたはNであり、
RまたはR′は、それぞれ独立して、水素、ヒドロキシ、ハロゲン、C6-12アリール、C5-12ヘテロアリール、-C1-6アルキル、-C3-10シクロアルキル、-C1-6アルコキシ、-C2-6アルケニルまたは-C2-6アルキニル(ここで、-C1-6アルキル、-C3-10シクロアルキル、-C2-6アルケニルまたは-C2-6アルキニルは、C1-6ハロアルキル、ハロゲン、シアノ、ニトロ、C6-12アリール、またはC5-12ヘテロアリールから独立して選択される0個~3個の置換基により置換されてもよい)であり;
nおよびn′は、それぞれ独立して、0~13の整数であり;
mおよびyは、それぞれ独立して、0~2の整数であり、
R1またはR2は、それぞれ独立して、水素、C1-6アルキル、C1-6アルコキシ、C1-6アルコキシカルボニル、ハロC1-6アルキル、C2-6アルケニル、C4-15のモノサイクリックまたはビサイクリック環(これは、C3-10シクロアルキル;C6-10アリール;N、OおよびSから独立して選択される、0個~3個のヘテロ原子を含有する、5員または6員の飽和または部分的飽和のヘテロ環;N、OおよびSから独立して選択される、0個~3個のヘテロ原子(前記ヘテロ原子のうち2個以上がOまたはSであるわけではない)を含有する5員または6員の芳香族ヘテロ環;またはN、OおよびSから独立して選択される、0個~3個のヘテロ原子を含有する、7員~15員の飽和、部分的飽和、または不飽和のヘテロ環)であり;
前記R1およびR2は、5員~12員のモノサイクリックまたはビサイクリック環を形成しつつ連結され得る)
のうちいずれか1つである化合物である
請求項1に記載の化合物またはその薬学的に許容可能な塩。 - 前記L1は、直接連結されるか、C1-3アルキレンであり;
前記Ar1は、C1-6直鎖または分岐鎖アルキル、ナフチル、フェニル、ナフチル、アントラセニル、フェナントレニル、ピレニル、フラニル、インドール、クロモン、キノリン、カルバゾールまたはチオフェニルであり、これらは、置換されないか、ヒドロキシ、ハロゲン、C1-6アルキル、C3-10シクロアルキル、C1-6アルコキシ、C1-6ハロアルキル、C1-6ハロアルコキシ、C2-6アルケニル、-C2-6アルキニル、C6-12アリールまたはC5-12ヘテロアリールのうち少なくとも1つで置換されてもよく;
前記mは、1であり、
前記yは、1または2であり、
前記R1またはR2は、それぞれ独立して、水素、C1-6アルキル、ベンジル、ナフチルアルキル、ベンゾフラニルアルキル、キノリニルアルキル、ピリジニルアルキル、シクロヘキシルアルキル、チオフェニルアルキル、ピロリルアルキル、フラニルアルキルまたはベンゾチオフェニルアルキルであり、これらは、置換されないか、それぞれ独立して、C1-6アルキル、C3-6シクロアルキル、C6-12アリール、ヒドロキシ、ハロゲン、C1-6アルコキシ、C1-6ハロアルキル、またはC1-6ハロアルコキシのうち少なくとも1つで置換されてもよく;
前記R1およびR2は、5員~12員のモノサイクリックまたはビサイクリック環を形成しつつ連結され得る
請求項1に記載の化合物またはその薬学的に許容可能な塩。 - 前記L1は、C1-3アルキレンであり;
前記Ar1は、
C1-6直鎖または分岐鎖アルキル、
前記RおよびR′は、それぞれ独立して、水素、ハロゲン、C6-12アリール、C5-12ヘテロアリール、-C1-6アルキル、-C3-10シクロアルキル、-C1-6アルコキシ、-C2-6アルケニルまたは-C2-6アルキニル(ここで、-C1-6アルキル、-C3-10シクロアルキル、-C1-6アルコキシ、-C2-6アルケニルまたは-C2-6アルキニルは、C1-6ハロアルキル、ハロゲン、シアノ、ニトロ、C6-12アリール、またはC5-12ヘテロアリールから独立して選択される0個~3個の置換基により置換されてもよい)であり;
前記mは、1であり、
前記yは、1または2であり、
前記R1またはR2は、それぞれ独立して、水素、C1-6直鎖または分岐鎖アルキル、
前記R1およびR2は、5員~12員のモノサイクリックまたはビサイクリック環を形成しつつ連結され得る
請求項1に記載の化合物またはその薬学的に許容可能な塩。 - 請求項1から5のいずれか一項に記載の化合物またはその薬学的に許容可能な塩、水和物、溶媒和物、構造異性体、光学異性体、立体異性体、またはこれらの組み合わせを含むがんの予防または治療用薬学組成物。
- 請求項1から5のいずれか一項に記載の化合物またはその薬学的に許容可能な塩、水和物、溶媒和物、構造異性体、光学異性体、立体異性体、またはこれらの組み合わせを含む耐性がんの予防または治療用薬学組成物。
- 前記組成物は、
SERCAタンパク質発現を抑制するものである
請求項7に記載の耐性がんの予防または治療用薬学組成物。 - 前記耐性がんは、
抗がん薬物に対する耐性を有するか、放射能に対する耐性を有する
請求項7に記載の耐性がんの予防または治療用薬学組成物。 - 前記抗がん薬物は、
ナイトロジェンマスタード、イマチニブ、オキサリプラチン、リツキシマブ、エルロチニブ、ネラチニブ、ラパチニブ、ゲフィチニブ 、バンデタニブ、ニロチニブ、セマサニブ、ボスチニブ、アキシチニブ、マシチニブ、セジラニブ、レスタウルチニブ、トラスツズマブ、ゲフィチニブ、ボルテゾミブ、スニチニブ、パゾパニブ、トセラニブ、ニンテダニブ、レゴラフェニブ、セマクサニブ、チボザニブ、ポナチニブ、カボザンチニブカルボプラチン、ソラフェニブ、レンバチニブ、ベバシズマブ、シスプラチン、セツキシマブ、ビスカムアルバム、アスパラギナーゼ、トレチノイン、ヒドロキシカルバミド、ダサチニブ、エストラムスチン、ゲムツズマブオゾガマイシン、イブリツモマブチウキセタン、ヘプタプラチン、メチルアミノレブリン酸、アムサクリン、アレムツズマブ、プロカルバジン、アルプロスタジル、硝酸ホルミウムキトサン、ゲムシタビン、ドキシフルリジン、ペメトレキセド、テガフール、カペシタビン、ギメラシン、オテラシル、アザシチジン、メトトレキサート、ウラシル、シタラビン、5-フルオロウラシル、フルダラビン、エノシタビン、フルタミド、カペシタビン、デシタビン、メルカプトプリン、チオグアニン、クラドリビン、カルモフール、ラルチトレキセド、ドセタキセル、パクリタキセル、カバジタキセル、イリノテカン、ベロテカン、トポテカン、ビノレルビン、エトポシド、ビンクリスチン、ビンブラスチン、テニポシド、ドキソルビシン、イダルビシン、エピルビシン、ミトキサントロン、マイトマイシン、ブレオマイシン、ダウノルビシン、ダクチノマイシン、ピラルビシン、アクラルビシン、ペプロマイシン、テムシロリムス、テモゾロミド、ブスルファン、イホスファミド、シクロホスファミド、メルファラン、アルトレタミン、ダカルバジン、チオテパ、ニムスチン、クロラムブシル、ミトラクトル、ロイコボリン、トレトニン、エキセメスタン、アミノグルテチミド、アナグレリド、オラパリブ、ナベルビン、ファドロゾール、タモキシフェン、トレミフェン、テストトラクトン、アナストロゾール、レトロゾール、ボロゾール、ビカルタミド、ロムスチン、ボリノスタット、エンチノスタットおよびカルムスチンからなる群から選ばれた少なくとも1つである
請求項9に記載の耐性がんの予防または治療用薬学組成物。 - 前記抗がん薬物は、前記化学式1で表される化合物またはその薬学的に許容可能な塩と1:0.001~1:1000のモル濃度比で含まれる
請求項9に記載の耐性がんの予防または治療用薬学組成物。 - 前記耐性がんは、
卵巣がん、大腸がん、すい臓がん、胃がん、肝がん、乳がん、子宮頸がん、甲状腺がん、副甲状腺がん、肺がん、非小細胞性肺がん、前立腺がん、胆のうがん、胆道がん、血液がん、膀胱がん、腎臓がん、黒色腫、結腸がん、骨がん、皮膚がん、頭頸部がん、子宮がん、直腸がん、脳がん、肛門付近がん、ラッパ管がん腫、子宮内膜がん腫、膣がん、陰門がん腫、食道がん、小腸がん、内分泌腺がん、副腎がん、軟組織肉腫、尿道がん、陰茎がん、輸尿管がん、腎臓細胞がん腫、腎臓骨盤がん腫、血液がん、中枢神経系(central nervous system;CNS)腫瘍、脊髄腫瘍、脳幹神経膠腫および脳下垂体腺腫からなる群から選ばれた少なくとも1つである
請求項9に記載の耐性がんの予防または治療用薬学組成物。 - 請求項1から5のいずれか一項に記載の化合物またはその薬学的に許容可能な塩、水和物、溶媒和物、構造異性体、光学異性体、立体異性体、またはこれらの組み合わせ;の治療学的有効量をがんを有する個体に投与することを含む、がんを治療する方法。
- 請求項1から5のいずれか一項に記載の化合物またはその薬学的に許容可能な塩、水和物、溶媒和物、構造異性体、光学異性体、立体異性体、またはこれらの組み合わせ;の治療学的有効量を耐性がんを有する個体に投与することを含む、腫瘍学的療法に対して耐性を示すがんを治療する方法。
- がんまたは増殖性疾患の治療に有用な化学療法剤を同時に、個別的に、または順次に投与することを含む
請求項14に記載の腫瘍学的療法に対して耐性を示すがんを治療する方法。 - 請求項1から5のいずれか一項に記載の化合物またはその薬学的に許容可能な塩をがんまたは耐性がんの治療のための薬剤を製造するための用途。
- 請求項1から5のいずれか一項に記載の化合物またはその薬学的に許容可能な塩、水和物、溶媒和物、構造異性体、光学異性体、立体異性体、またはこれらの組み合わせを幹細胞性がんの治療のための薬剤を製造するための用途。
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