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    • 3. 发明授权
    • Breast cancer resistance protein (BCRP) inhibitor
    • 乳腺癌抗性蛋白(BCRP)抑制剂
    • US07371773B2
    • 2008-05-13
    • US10544064
    • 2004-02-03
    • Ryuta YamazakiYukiko NishiyamaTomio FurutaTakeshi MatsuzakiHiroshi HatanoOh YoshidaMasato NagaokaRitsuo AiyamaShusuke HashimotoYoshikazu Sugimoto
    • Ryuta YamazakiYukiko NishiyamaTomio FurutaTakeshi MatsuzakiHiroshi HatanoOh YoshidaMasato NagaokaRitsuo AiyamaShusuke HashimotoYoshikazu Sugimoto
    • A61K31/415
    • C07D211/58A61K31/277A61K31/7034C07C255/37C07D317/60
    • The invention provides a drug which inhibits BCRP.A breast cancer resistance protein inhibitor containing, as an active ingredient, a diphenylacrylonitrile derivative represented by the following formula (1): [wherein, each of 8 R's, which are the same or different from one another, represents a hydrogen atom, a hydroxyl group, a nitro group, an amino group, an acetylamino group (—NHCOCH3 group); a cyano group (—CN group); a formyl group (—CHO group), —COOR1 (R1 is hydrogen or C1-C4 alkyl), —O(CH2)nCOOR2 (n=1−7: R2 is hydrogen or C1-C4 alkyl), —OOCCH2CH2COOR3 (R3 is hydrogen, C1-C4 alkyl, (Z)-2-(3,4-dimethoxy-phenyl)-3-(4-hydroxy-phenyl)-acrylonitrile, or glycopyranosyl), a C1-C8 alkoxy group, a C1-C4 alkyl group, a halogen atom, a C1-C4 alkoxy C1-C4 alkoxy C1-C4 alkoxy group, a C2-C8 acyloxy group, a C2-C8 halogenoacyloxy group, a methylenedioxy group, a trifluoromethyl group, a phosphate group (i.e., —OP(O) (OH)2) or a salt thereof, a sulfate group (i.e., —OSO3H) or a salt thereof, a glycopyranosyl group or a salt thereof, a phosphate ester of a glycopyranosyl group or a salt of the ester, a sulfate ester of a glycopyranosyl group or a salt of the ester, or a piperidinopiperidinocarbonyloxy group], an ester thereof, or a salt thereof.
    • 本发明提供抑制BCRP的药物。 作为活性成分,含有下述式(1)表示的二苯基丙烯腈衍生物的乳
      球癌抗性蛋白质抑制剂:[其中,8个相同或不同的8个R代表氢原子,羟基 基团,硝基,氨基,乙酰氨基(-NHCOCH 3 SO 3); 氰基(-CN基); 甲酰基(-CHO基),-COOR 1(R 1是氢或C 1 -C 4烷基),-O(CH 2) )nOR 2(n = 1-7:R 2是氢或C 1 -C 4烷基),-OOCCH 2 (R 3)是氢,C 1 -C 4烷基,(Z)-2-(3,4-二氯苯基) 二甲氧基 - 苯基)-3-(4-羟基 - 苯基) - 丙烯腈或糖吡喃糖基),C1-C8烷氧基,C1-C4烷基,卤素原子,C1-C4烷氧基C1-C4烷氧基C1- C4烷氧基,C2-C8酰氧基,C2-C8卤代酰氧基,亚甲二氧基,三氟甲基,磷酸基(即-OP(O)(OH)2))或 其盐,硫酸基(即-OSO 3 H)或其盐,糖吡喃糖基或其盐,糖吡喃糖基的磷酸酯或酯的盐, 糖吡喃糖基的硫酸酯或酯的盐或哌啶子基哌啶羰基氧基],其酯或其盐。
    • 6. 发明申请
    • Breast cancer resistance protein (bcrp) inhibitor
    • 乳腺癌抗性蛋白(bcrp)抑制剂
    • US20060128636A1
    • 2006-06-15
    • US10544064
    • 2004-02-03
    • Ryuta YamazakiYukiko NishiyamaTomio FurutaTakeshi MatsuzakiHiroshi HatanoOh YoshidaMasato NagaokaRitsuo AiyamaShusuke HashimotoYoshikazu Sugimoto
    • Ryuta YamazakiYukiko NishiyamaTomio FurutaTakeshi MatsuzakiHiroshi HatanoOh YoshidaMasato NagaokaRitsuo AiyamaShusuke HashimotoYoshikazu Sugimoto
    • A61K31/7034A61K31/277A61K31/66
    • C07D211/58A61K31/277A61K31/7034C07C255/37C07D317/60
    • The invention provides a drug which inhibits BCRP. A breast cancer resistance protein inhibitor containing, as an active ingredient, a diphenylacrylonitrile derivative represented by the following formula (1): [wherein, each of 8 R's, which are the same or different from one another, represents a hydrogen atom, a hydroxyl group, a nitro group, an amino group, an acetylamino group (—NHCOCH3 group); a cyano group (—CN group); a formyl group (—CHO group), —COOR1 (R1 is hydrogen or C1-C4 alkyl), —O(CH2)nCOOR2 (n=1−7: R2 is hydrogen or C1-C4 alkyl), —OOCCH2CH2COOR3 (R3 is hydrogen, C1-C4 alkyl, (Z)-2-(3,4-dimethoxy-phenyl)-3-(4-hydroxy-phenyl)-acrylonitrile, or glycopyranosyl), a C1-C8 alkoxy group, a C1-C4 alkyl group, a halogen atom, a C1-C4 alkoxy C1-C4 alkoxy C1-C4 alkoxy group, a C2-C8 acyloxy group, a C2-C8 halogenoacyloxy group, a methylenedioxy group, a trifluoromethyl group, a phosphate group (i.e., —OP(O) (OH)2) or a salt thereof, a sulfate group (i.e., —OSO3H) or a salt thereof, a glycopyranosyl group or a salt thereof, a phosphate ester of a glycopyranosyl group or a salt of the ester, a sulfate ester of a glycopyranosyl group or a salt of the ester, or a piperidinopiperidinocarbonyloxy group], an ester thereof, or a salt thereof.
    • 本发明提供抑制BCRP的药物。 作为活性成分,含有下述式(1)表示的二苯基丙烯腈衍生物的乳
      球癌抗性蛋白质抑制剂:[其中,8个相同或不同的8个R代表氢原子,羟基 基团,硝基,氨基,乙酰氨基(-NHCOCH 3 SO 3); 氰基(-CN基); 甲酰基(-CHO基),-COOR 1(R 1是氢或C 1 -C 4烷基),-O(CH 2) )nOR 2(n = 1-7:R 2是氢或C 1 -C 4烷基),-OOCCH 2 (R 3)是氢,C 1 -C 4烷基,(Z)-2-(3,4-二氯苯基) 二甲氧基 - 苯基)-3-(4-羟基 - 苯基) - 丙烯腈或糖吡喃糖基),C1-C8烷氧基,C1-C4烷基,卤素原子,C1-C4烷氧基C1-C4烷氧基C1- C4烷氧基,C2-C8酰氧基,C2-C8卤代酰氧基,亚甲二氧基,三氟甲基,磷酸基(即-OP(O)(OH)2))或 其盐,硫酸基(即-OSO 3 H)或其盐,糖吡喃糖基或其盐,糖吡喃糖基的磷酸酯或酯的盐, 糖吡喃糖基的硫酸酯或酯的盐或哌啶子基哌啶羰基氧基],其酯或其盐。
    • 8. 发明授权
    • Camptothecin derivatives, preparations thereof and antitumor agents
    • 喜树碱衍生物,其制剂和抗肿瘤剂
    • US5843954A
    • 1998-12-01
    • US976398
    • 1997-11-21
    • Takashi YaegashiSeigo SawadaTomio FurutaTeruo Yokokura
    • Takashi YaegashiSeigo SawadaTomio FurutaTeruo Yokokura
    • A61K31/47A61K31/4745A61P35/00C07D209/00C07D221/00C07D471/14C07D487/02
    • C07D471/14
    • New camptothecin derivatives of the general formula (1): ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group, R.sup.2 represents a hydrogen or a C.sub.1 -C.sub.6 alkoxy group, R.sup.3 represents a hydrogen or halogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, C.sub.2 -C.sub.6 acyloxy or methoxyethoxymethoxy group, R.sup.4 represents a hydrogen or halogen atom, and R.sup.5 represents a C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 unsaturated alkyl, alkylthioalkyl, alkoxyalkyl, pyridyl or substituted phenyl group, with the proviso that all of the R.sup.2, R.sup.3 and R.sup.4 substituents should not be a hydrogen atom, and a process for preparing the new camptothecin derivatives by subjecting the camptothecin derivatives of the general formula (2): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as given above, to the reaction with N,N-dimethylethylenediamine without solvent to open the E-lactone ring followed by acylation of 17-hydroxyl group with corresponding acylating agents and an antitumor agent containing the same as an active ingredient.
    • (1)的新喜树碱衍生物:其中R1表示氢原子或C1-C6烷基,R2表示氢或C1-C6烷氧基,R3表示氢或卤素原子 或C 1 -C 6烷基,C 1 -C 6烷氧基,羟基,C 2 -C 6酰氧基或甲氧基乙氧基甲氧基,R 4表示氢或卤素原子,R 5表示C 1 -C 6烷基,C 3 -C 6不饱和烷基,烷硫基烷基,烷氧基烷基,吡啶基 或取代的苯基,条件是所有的R 2,R 3和R 4取代基不应该是氢原子,以及通过使通式(2)的喜树碱衍生物进行制备来制备新的喜树碱衍生物的方法: (2)其中R 1,R 2,R 3和R 4具有与上述相同的含义,与没有溶剂的N,N-二甲基乙二胺反应以打开E-内酯环,随后用相应的酰化剂酰化17-羟基, 含有与活性物质相同的抗肿瘤剂 e成分。