公开(公告)号：US08791125B2

公开(公告)日：2014-07-29

申请号：US13053798

申请日：2011-03-22

申请人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

发明人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D487/00

CPC分类号： C07D487/04 ,  A61K31/4162 ,  A61K31/519

摘要： The invention relates to compounds of a general formula (I): wherein Ar1 is an optionally-substituted aryl or heteroaromatic group; R1 is an optionally-substituted lower alkyl, lower alkenyl, lower alkynyl or cyclo-lower alkyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R2 is a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R3 is a hydrogen atom or a lower alkyl group; R4 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group of —N(R1k)R1m; T and U are a nitrogen atom or a methine group, etc. The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.

摘要翻译： 本发明涉及通式（I）的化合物：其中Ar1是任选取代的芳基或杂芳基; R 1是任选取代的低级烷基，低级烯基，低级炔基或环低级烷基，或者是任选具有取代基的芳基，芳烷基或杂芳基; R2是氢原子，低级烷基，低级烯基或低级炔基，或者是任选具有取代基的芳基，芳烷基或杂芳基; R3是氢原子或低级烷基; R4是氢原子，卤素原子，羟基，低级烷基或-N（R1k）R1m基团; T和U是氮原子或次甲基等。本发明的化合物具有优异的韦尔激酶抑制作用，因此可用于药物领域，特别是治疗各种癌症。

公开(公告)号：US07709475B2

公开(公告)日：2010-05-04

申请号：US11596735

申请日：2005-05-19

申请人： Yoshikazu Iwasawa ,  Jun Shibata ,  Tadashi Shimamura ,  Hideki Kurihara ,  Takashi Mita ,  Nobuhiko Kawanishi ,  Takashi Hashihayata ,  Mikako Kawamura ,  Takeshi Sagara ,  Sachie Arai ,  Hiroshi Hirai

发明人： Yoshikazu Iwasawa ,  Jun Shibata ,  Tadashi Shimamura ,  Hideki Kurihara ,  Takashi Mita ,  Nobuhiko Kawanishi ,  Takashi Hashihayata ,  Mikako Kawamura ,  Takeshi Sagara ,  Sachie Arai ,  Hiroshi Hirai

IPC分类号： C07D417/12 ,  A61K31/506 ,  C07D417/14 ,  C07D491/08

CPC分类号： C07D417/14 ,  C07D417/12 ,  C07D491/08

摘要： The present invention relates to a compound represented by Formula [I]: wherein X is O, S, NH or CH2; Y1, Y2, Y3, Y4 and Y5, which may be identical or different, are each CH or N; however, at least one of Y1, Y2, Y3, Y4 and Y5 is N; Z1 and Z2, which may be identical or different, are each CH or N; n is an integer from 1 to 3; R1 is a C3-C8 cycloalkyl group, a C6-C10 aryl group, an aliphatic heterocyclic ring or an aromatic heterocyclic ring, or a bicyclic aliphatic saturated hydrocarbon group; R2 and R3, which may be identical or different, are each a hydrogen atom, a lower alkyl group, a lower alkenyl group, a C3-C8 cycloalkyl group, a C6-C10 aryl group, an aromatic heterocyclic ring, or the like; and R4 is a hydrogen atom, a lower alkyl group, a C3-C6 cycloalkyl group or the like, or a pharmaceutically acceptable salt or ester thereof, and a selective inhibitor against Cdk4 and/or Cdk6 or an anticancer agent containing the compound or a pharmaceutically acceptable salt or ester thereof.

摘要翻译： 本发明涉及由式[I]表示的化合物：其中X是O，S，NH或CH 2; Y1，Y2，Y3，Y4和Y5可以相同或不同，分别为CH或N; 然而，Y 1，Y 2，Y 3，Y 4和Y 5中的至少一个为N; 可以相同或不同的Z 1和Z 2各自为CH或N; n为1〜3的整数， R1是C3-C8环烷基，C6-C10芳基，脂族杂环或芳族杂环，或双环脂族饱和烃基; R2和R3可以相同或不同，分别为氢原子，低级烷基，低级烯基，C3-C8环烷基，C6-C10芳基，芳族杂环等; R4为氢原子，低级烷基，C3-C6环烷基等，或其药学上可接受的盐或酯，以及对Cdk4和/或Cdk6的选择性抑制剂或含有该化合物或 其药学上可接受的盐或酯。

公开(公告)号：US20070254892A1

公开(公告)日：2007-11-01

申请号：US11789548

申请日：2007-04-25

申请人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

发明人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

IPC分类号： A61K31/519 ,  C07D487/02

CPC分类号： C07D487/04 ,  A61K31/4162 ,  A61K31/519

摘要： The invention relates to compounds of a general formula (I): wherein Ar1 is an optionally-substituted aryl or heteroaromatic group; R1 is an optionally-substituted lower alkyl, lower alkenyl, lower alkynyl or cyclo-lower alkyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R2 is a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R3 is a hydrogen atom or a lower alkyl group; R4 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group of —N(R1k)R1m; T and U are a nitrogen atom or a methine group, etc.The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.

摘要翻译： 本发明涉及通式（I）的化合物：其中Ar 1是任选取代的芳基或杂芳基; R 1是任选取代的低级烷基，低级烯基，低级炔基或环 - 低级烷基，或者是任选具有取代基的芳基，芳烷基或杂芳族基团; R 2是氢原子，低级烷基，低级烯基或低级炔基，或者是任选具有取代基的芳基，芳烷基或杂芳基; R 3是氢原子或低级烷基; R 4是氢原子，卤素原子，羟基，低级烷基或-N（R 1）1个基团）的基团， SUP>; T和U是氮原子或次甲基等。本发明的化合物具有优异的韦尔激酶抑制作用，因此可用于药物领域，特别是治疗各种癌症。

公开(公告)号：US6033847A

公开(公告)日：2000-03-07

申请号：US384106

申请日：1995-02-06

申请人： Charles J. Sherr ,  James Downing ,  Hiroshi Hirai ,  Tsukasa Okuda

发明人： Charles J. Sherr ,  James Downing ,  Hiroshi Hirai ,  Tsukasa Okuda

IPC分类号： G01N33/53 ,  A61K31/70 ,  A61K48/00 ,  A61P35/00 ,  C07K14/47 ,  C07K14/52 ,  C07K16/24 ,  C12N15/09 ,  C12N15/12 ,  C12Q1/68 ,  G01N33/15 ,  G01N33/574 ,  C07H21/00 ,  C07K14/435 ,  C12N15/85

CPC分类号： C07K14/47 ,  A01K2217/05 ,  C07K2319/00

摘要： Members of the InK4 (Inhibitors of CDK4) family inhibit the activities of specific cyclin D-dependent kinases (CDK4 and/or CDK6), thereby arresting cell cycle progression in G1 phase and preventing chromosomal DNA replication. Disclosed herein are novel mammalian InK4 family members, having apparent molecular masses of 18,000 and 19,000 daltons, designated "InK4c-p18" and "InK4d-p19," respectively, or simply "p18" and "p19." In particular, the invention provides p19 genes and proteins isolated from murine or human cells and p18 genes and proteins from murine cells. When constitutively expressed in cells, p19 inhibits cyclin D-dependent kinase activity in vivo and induces G1 phase arrest. Materials and methods disclosed herein include (1) nucleic acids that encode p18 or p19; (2) methods for detecting nucleic acids encoding p18 or p19 proteins; (3) methods for producing p18 or p19 proteins using nucleic acids that encode p18 or p19, respectively; (4) purified pl8 or p19 proteins and peptide fragments, oligopeptides, or fusion proteins derived therefrom; (5) methods of inhibiting cells from replicating their chromosomal DNA using purified p18 or p19 proteins or derivatives thereof; (6) antibodies that specifically bind p18 or p19; (7) methods for detecting p18 and p19 proteins; (8) methods of stimulating cell growth by blocking p18 or p19 expression via antisense oligonucleotides; (9) methods of gene therapy using nucleic acids that encode p18 or p19; and (10) methods of making transgenic non-human animals that have alterations in the gene encoding p18 or p19, or in both genes.

摘要翻译： InK4（CDK4抑制剂）家族的成员抑制特异性细胞周期蛋白D依赖性激酶（CDK4和/或CDK6）的活性，从而阻止G1期的细胞周期进程并防止染色体DNA复制。 本文公开了新颖的哺乳动物InK4家族成员，其分子量分别为18,000和19,000道尔顿，分别称为“InK4c-p18”和“InK4d-p19”，或简称为“p18”和“p19”。 特别地，本发明提供从鼠或人细胞分离的p19基因和蛋白质，以及来自鼠细胞的p18基因和蛋白质。 当细胞中组成型表达时，p19在体内抑制细胞周期蛋白D依赖性激酶活性，并诱导G1期停滞。 本文公开的材料和方法包括（1）编码p18或p19的核酸; （2）检测编码p18或p19蛋白质的核酸的方法; （3）分别使用编码p18或p19的核酸产生p18或p19蛋白的方法; （4）纯化的p18或p19蛋白质和肽片段，寡肽或从其衍生的融合蛋白; （5）使用纯化的p18或p19蛋白或其衍生物抑制细胞复制染色体DNA的方法; （6）特异性结合p18或p19的抗体; （7）检测p18和p19蛋白的方法; （8）通过反义寡核苷酸阻断p18或p19表达刺激细胞生长的方法; （9）使用编码p18或p19的核酸进行基因治疗的方法; 和（10）制备在编码p18或p19的基因或两种基因中具有改变的转基因非人动物的方法。

公开(公告)号：US4019610A

公开(公告)日：1977-04-26

申请号：US595996

申请日：1975-07-15

申请人： Hiroshi Hirai

发明人： Hiroshi Hirai

IPC分类号： F16D55/00 ,  F16D55/2265 ,  F16D55/227 ,  F16D55/224

CPC分类号： F16D55/22655 ,  F16D55/227 ,  F16D2055/0091

摘要： The present invention relates to a floating caliper disc brake particularly used for large vehicles and industrial machineries, in detail, wherein a pair of left and right pins fixed to a support are arranged to guide inner and outer friction pads towards a disc and are removable to replace said friction pads as required, therefore, simplifying exchange of friction pads, and a pair of the pins are formed separately to receive the braking torque generated on the respective inner and outer friction pads so as to minimize strength of individual pin.

摘要翻译： 本发明涉及一种特别用于大型车辆和工业机械的浮动卡钳式盘式制动器，其特征在于，一对固定到支撑件上的左右销钉被布置成将内部和外部摩擦垫朝向盘引导， 根据需要更换所述摩擦垫，因此，简化了摩擦垫的更换，并且一对销分别形成以接收在相应的内摩擦垫和外摩擦垫上产生的制动扭矩，从而使单个销的强度最小化。

公开(公告)号：US08481503B2

公开(公告)日：2013-07-09

申请号：US13254108

申请日：2010-02-23

申请人： Mark E. Layton ,  Hiroshi Hirai ,  Hidehito Kotani

发明人： Mark E. Layton ,  Hiroshi Hirai ,  Hidehito Kotani

IPC分类号： A01N43/04 ,  A61K31/70

CPC分类号： A61K31/495 ,  A61K31/4196 ,  A61K31/50 ,  A61K2300/00

摘要： The invention relates to combination anticancer therapy with certain Akt inhibitor and other anticancer agents such as anticancer antimetabolites, anticancer antibiotics, plant-derived anticancer agents, anticancer platinum-coordinated complex compounds, anticancer camptothecin derivatives and anticancer tyrosine kinase inhibitors.

摘要翻译： 本发明涉及与某些Akt抑制剂和其他抗癌剂如抗癌抗代谢药，抗癌抗生素，植物衍生抗癌剂，抗癌铂配位化合物，抗癌喜树碱衍生物和抗癌酪氨酸激酶抑制剂的组合抗癌治疗。

公开(公告)号：US20120157342A1

公开(公告)日：2012-06-21

申请号：US13393915

申请日：2010-08-26

申请人： Shinji Mizuarai ,  Hiraku Itadani ,  Kazunori Yamanaka ,  Toshihide Nishibata ,  Tsuyoshi Arai ,  Hiroshi Hirai ,  Hidehito Kotani

发明人： Shinji Mizuarai ,  Hiraku Itadani ,  Kazunori Yamanaka ,  Toshihide Nishibata ,  Tsuyoshi Arai ,  Hiroshi Hirai ,  Hidehito Kotani

IPC分类号： C12Q1/68 ,  C40B30/04

CPC分类号： C12Q1/6883 ,  C12Q2600/118

摘要： The present invention provides the identification of biomarker gene sets whose expression levels are useful for predicting a patient's response to a therapeutically effective dose of a Wee1 inhibitor as well the ability to predict said response prior to dosing with the Wee1 inhibitor. Additional uses are also disclosed in the specification.

摘要翻译： 本发明提供了生物标记基因组的鉴定，其表达水平可用于预测患者对治疗有效剂量的Wee1抑制剂的反应以及在施用Wee1抑制剂之前预测所述应答的能力。 附加用途也在说明书中公开。

公开(公告)号：US08053878B2

公开(公告)日：2011-11-08

申请号：US11979768

申请日：2007-11-08

申请人： Hiroki Iwamura ,  Naoto Ozawa ,  Hiroshi Hirai

发明人： Hiroki Iwamura ,  Naoto Ozawa ,  Hiroshi Hirai

IPC分类号： H01L23/488

CPC分类号： G01R1/0416 ,  G01R31/2886 ,  H01L22/34 ,  H01L25/105 ,  H01L2224/48091 ,  H01L2225/1023 ,  H01L2225/1058 ,  H01L2924/19105 ,  H01L2924/30107 ,  H01L2924/3011 ,  H01L2924/00014 ,  H01L2924/00

摘要： A substrate including therein a plurality of conductor layers laminated via insulating layers, the substrate mounting at least one semiconductor integrated circuit, wherein the substrate includes a first electrode terminal connected to the semiconductor integrated circuit, a second electrode terminal connected to a terminal on an upper substrate arranged in a layer over the substrate, and on at least part of the perimeter of the first and second electrode terminals, a third electrode terminal located outside the outer edge of the upper substrate.

摘要翻译： 一种衬底，包括通过绝缘层层压的多个导体层，所述衬底安装至少一个半导体集成电路，其中所述衬底包括连接到所述半导体集成电路的第一电极端子，连接到上部的端子的第二电极端子 衬底，其布置在衬底上的层中，并且在第一和第二电极端子的周边的至少一部分上，位于上衬底的外边缘外侧的第三电极端子。

公开(公告)号：US20110189130A1

公开(公告)日：2011-08-04

申请号：US13053798

申请日：2011-03-22

申请人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

发明人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

IPC分类号： A61K31/519 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K31/664 ,  A61K31/675 ,  A61K31/7008 ,  A61K31/7076 ,  A61K31/52 ,  A61K31/708 ,  A61K31/704 ,  A61K33/24 ,  A61K39/395 ,  A61K38/21 ,  A61P35/00 ,  A61P35/02

CPC分类号： C07D487/04 ,  A61K31/4162 ,  A61K31/519

摘要： The invention relates to compounds of a general formula (I): wherein Ar1 is an optionally-substituted aryl or heteroaromatic group; R1 is an optionally-substituted lower alkyl, lower alkenyl, lower alkynyl or cyclo-lower alkyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R2 is a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R3 is a hydrogen atom or a lower alkyl group; R4 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group of —N(R1k)R1m; T and U are a nitrogen atom or a methine group, etc.The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.

摘要翻译： 本发明涉及通式（I）的化合物：其中Ar1是任选取代的芳基或杂芳基; R 1是任选取代的低级烷基，低级烯基，低级炔基或环低级烷基，或者是任选具有取代基的芳基，芳烷基或杂芳基; R2是氢原子，低级烷基，低级烯基或低级炔基，或者是任选具有取代基的芳基，芳烷基或杂芳基; R3是氢原子或低级烷基; R4是氢原子，卤素原子，羟基，低级烷基或-N（R1k）R1m基团; T和U是氮原子或次甲基等。本发明的化合物具有优异的韦尔激酶抑制作用，因此可用于药物领域，特别是治疗各种癌症。

公开(公告)号：US07935708B2

公开(公告)日：2011-05-03

申请号：US12226707

申请日：2007-04-25

申请人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

发明人： Takeshi Sagara ,  Sachie Otsuki ,  Satoshi Sunami ,  Toshihiro Sakamoto ,  Kenji Niiyama ,  Fuyuki Yamamoto ,  Takashi Yoshizumi ,  Hidetomo Furuyama ,  Yasuhiro Goto ,  Makoto Bamba ,  Keiji Takahashi ,  Hiroshi Hirai ,  Toshihide Nishibata

IPC分类号： A01N43/90 ,  A01N43/56 ,  A61K31/519 ,  A61K31/415 ,  C07D487/00 ,  C07D403/02

CPC分类号： C07D487/04 ,  A61K31/4162 ,  A61K31/519

摘要： The invention relates to compounds of a general formula (I): wherein Ar1 is an optionally-substituted aryl or heteroaromatic group; R1 is an optionally-substituted lower alkyl, lower alkenyl, lower alkynyl or cyclo-lower alkyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R2 is a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R3 is a hydrogen atom or a lower alkyl group; R4 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group of —N(R1k)R1m; T and U are a nitrogen atom or a methine group, etc. The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.

摘要翻译： 本发明涉及通式（I）的化合物：其中Ar1是任选取代的芳基或杂芳基; R 1是任选取代的低级烷基，低级烯基，低级炔基或环低级烷基，或者是任选具有取代基的芳基，芳烷基或杂芳基; R2是氢原子，低级烷基，低级烯基或低级炔基，或者是任选具有取代基的芳基，芳烷基或杂芳基; R3是氢原子或低级烷基; R4是氢原子，卤素原子，羟基，低级烷基或-N（R1k）R1m基团; T和U是氮原子或次甲基等。本发明的化合物具有优异的韦尔激酶抑制作用，因此可用于药物领域，特别是治疗各种癌症。