公开(公告)号：US20050004149A1

公开(公告)日：2005-01-06

申请号：US10492905

申请日：2002-10-22

申请人： Hitoshi Harada ,  Osamu Asano ,  Masato Ueda ,  Shuhei Miyazawa ,  Yoshihiko Kotake ,  Yasuhiro Kabasawa ,  Masahiro Yasuda ,  Nobuyuki Yasuda ,  Daisuke Iida ,  Junichi Nagakawa ,  Kazuo Hirota ,  Makoto Nakagawa

发明人： Hitoshi Harada ,  Osamu Asano ,  Masato Ueda ,  Shuhei Miyazawa ,  Yoshihiko Kotake ,  Yasuhiro Kabasawa ,  Masahiro Yasuda ,  Nobuyuki Yasuda ,  Daisuke Iida ,  Junichi Nagakawa ,  Kazuo Hirota ,  Makoto Nakagawa

IPC分类号： A61K31/506 ,  A61P1/00 ,  A61P1/10 ,  A61P3/04 ,  A61P3/10 ,  A61P9/12 ,  A61P11/06 ,  A61P13/02 ,  A61P19/10 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D401/04 ,  C07D405/14 ,  C07D409/14 ,  C07

CPC分类号： C07D405/14 ,  A61K31/506 ,  C07D401/04 ,  C07D409/14

摘要： The present invention provides a novel pyrimidine compound having an excellent adenosine receptor (A1, A2A, A2B receptor) antagonistic action. More specifically, it provides a compound represented by the following formula, a salt thereof or a solvate of them. In the formula, R1 and R2 are the same as or different from each other and each represents a hydrogen atom, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a cycloalkenyl group having three to eight carbon atoms which may be substituted, a 5 to 14-membered non-aromatic heterocyclic group which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, an acyl group having one to six carbon atoms which may be substituted or an alkylsulfonyl group having one to six carbon atoms which may be substituted; R3 represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, a nitrogen atom which may be substituted, an oxygen atom which may be substituted or a sulfur atom which may be substituted; R4 represents an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted or a 5 to 14-membered non-aromatic heterocyclic group having at least one or more unsaturated bonds which may be substituted; and R5 represents an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted or a 5 to 14-membered aromatic heterocyclic group which may be substituted.

公开(公告)号：US07396836B2

公开(公告)日：2008-07-08

申请号：US10492905

申请日：2002-10-22

申请人： Hitoshi Harada ,  Masato Ueda ,  Yoshihiko Kotake ,  Masahiro Yasuda ,  Daisuke Iida ,  Junichi Nagakawa ,  Makoto Nakagawa

发明人： Hitoshi Harada ,  Masato Ueda ,  Yoshihiko Kotake ,  Masahiro Yasuda ,  Daisuke Iida ,  Junichi Nagakawa ,  Makoto Nakagawa

IPC分类号： A61K31/505 ,  C07D239/02

CPC分类号： C07D405/14 ,  A61K31/506 ,  C07D401/04 ,  C07D409/14

摘要： A compound having excellent adenosine receptor (A1, A2A, A2B receptor) antagonistic action, of the following formula, a salt thereof or a solvate of them: wherein, R1 and R2, same or different, each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, an aromatic hydrocarbon cyclic group, an acyl group or an alkylsulfonyl group, which groups may be substituted (except the hydrogen atom); R3 represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group, an alkenyl group, an alkynyl group, an aromatic hydrocarbon cyclic group, a nitrogen atom, an oxygen atom or a sulfur atom, which groups may be substituted (except the hydrogen atom, the halogen atom and the cyano group); R4 represents an aromatic hydrocarbon cyclic group which may be substituted, and R5 represents an aromatic hydrocarbon cyclic group which may be substituted.

摘要翻译： 具有优异的腺苷受体（A 1 H 1，A 2 A 2，A 2B 2受体）的化合物，下式的拮抗作用，其盐或 它们的溶剂化物：其中R 1，R 2和R 2相同或不同，各自表示氢原子，烷基，烯基，炔基， 环烷基，环烯基，芳香族烃基，酰基或烷基磺酰基，该基团可被取代（氢原子除外）。 R 3表示氢原子，卤素原子，氰基，烷基，烯基，炔基，芳族烃环状基团，氮原子，氧原子或硫原子 原子，该基团可被取代（氢原子，卤素原子和氰基除外）; R 4表示可以被取代的芳族烃环状基团，R 5表示可以被取代的芳族烃环状基团。

公开(公告)号：US20090030023A1

公开(公告)日：2009-01-29

申请号：US12054337

申请日：2008-03-24

申请人： Hitoshi Harada ,  Masato Ueda ,  Yoshihiko Kotake ,  Masahiro Yasuda ,  Daisuke Iida ,  Junichi Nagakawa ,  Makoto Nakagawa

发明人： Hitoshi Harada ,  Masato Ueda ,  Yoshihiko Kotake ,  Masahiro Yasuda ,  Daisuke Iida ,  Junichi Nagakawa ,  Makoto Nakagawa

IPC分类号： C07D239/42 ,  A61K31/505 ,  C12N5/00 ,  A61P1/00

CPC分类号： C07D405/14 ,  A61K31/506 ,  C07D401/04 ,  C07D409/14

摘要： A compound represented by the following formula (I), a salt, or a solvate thereof: wherein, R1 and R2 are the same as or different from each other and each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, a non-aromatic heterocyclic group, an aromatic hydrocarbon cyclic group, an aromatic heterocyclic group, an acyl group or an alkylsulfonyl group all of which may be substituted and wherein one, or both, of R1 or R2 is an aromatic, or non-aromatic, heterocyclic group which may be substituted; R3 represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group, an alkenyl group, an alkynyl group, an aromatic hydrocarbon cyclic group, an aromatic heterocyclic group, a nitrogen atom, an oxygen atom or a sulfur atom all of which may be substituted if possible; and R4 is a pyridyl group which may be substituted.

摘要翻译： 由下式（I）表示的化合物，其盐或溶剂化物：其中，R1和R2彼此相同或不同，各自表示氢原子，烷基，烯基，炔基 基团，环烷基，环烯基，非芳族杂环基，芳香族烃环基，芳香族杂环基，酰基或烷基磺酰基，其全部可以被取代，并且其中R1或 或R 2是可以被取代的芳族或非芳族杂环基; R3表示氢原子，卤原子，氰基，烷基，烯基，炔基，芳香族烃环基，芳香族杂环基，氮原子，氧原子或硫原子全部 如果可能的话可以被替代; R4为可被取代的吡啶基。

公开(公告)号：US07160892B2

公开(公告)日：2007-01-09

申请号：US10492547

申请日：2002-10-22

申请人： Hitoshi Harada ,  Osamu Asano ,  Masato Ueda ,  Shuhei Miyazawa ,  Yoshihiko Kotake ,  Yasuhiro Kabasawa ,  Masahiro Yasuda ,  Nobuyuki Yasuda

发明人： Hitoshi Harada ,  Osamu Asano ,  Masato Ueda ,  Shuhei Miyazawa ,  Yoshihiko Kotake ,  Yasuhiro Kabasawa ,  Masahiro Yasuda ,  Nobuyuki Yasuda

IPC分类号： A61K31/5377 ,  A61K31/513 ,  C07D417/02 ,  C07D413/02 ,  C07D43/02

CPC分类号： C07D239/34 ,  A61K31/513

摘要： The invention provides novel pyrimidone compounds exhibiting excellent antagonism against adenosine receptors (A1, A2A, and A2B receptors), particularly, compounds represented by the general formula (1), salts thereof, or solvates of both: (1) wherein R1 and R2 are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, a 5- to 14-membered nonaromatic heterocyclic group, a C6-14 aromatic hydrocarbon group, a 5- to 14-membered aromatic heterocyclic group, C1-6 acyl, or C1-6 alkylsulfonyl; R3 is hydrogen, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl; R4 is a C6-14 aromatic hydrocarbon group; a 5- to 14-membered aromatic heterocyclic group, or a 5- to 14-membered nonaromatic heterocyclic group having at least one unsaturated bond; and R5 is a C6-14 aromatic hydrocarbon group or a 5- to 14-membered aromatic heterocyclic group (with the proviso that every group except hydrogen may be substituted).

摘要翻译： 本发明提供了对腺苷受体（A 1 SUB，A 2A和A 2B 2受体）表现出优异拮抗作用的新型嘧啶酮化合物，特别是表示的化合物 通式（1）表示的盐，其盐或两者的溶剂合物：（1）其中R 1和R 2各自独立地为氢，C 1〜 C 1-6烷基，C 2-6链烯基，C 2-6炔基，C 3-8环烷基，C 1 -C 6 - 3-8环烯基，5至14元非芳族杂环基，C 6-14芳族烃基，5至14元芳族杂环基，C _{1-6酰基或C 1-6烷基磺酰基; R 3是氢，C 1-6烷基，C 2-6链烯基或C 2-6亚烷基， 炔基; R 4是C 6-14芳族烃基; 5至14元芳族杂环基或具有至少一个不饱和键的5至14元非芳族杂环基; 和R 5是C 6-14芳族烃基或5至14元芳族杂环基（条件是除了氢以外的每个基团可以被取代） 。}

公开(公告)号：US20070054876A1

公开(公告)日：2007-03-08

申请号：US11594132

申请日：2006-11-08

申请人： Masahiro Yasuda ,  Hitoshi Harada ,  Shuhei Miyazawa ,  Seiichi Kobayashi ,  Kokichi Harada ,  Takayuki Hida ,  Hisashi Shibata ,  Nobuyuki Yasuda ,  Osamu Asano ,  Yoshihiko Kotake

发明人： Masahiro Yasuda ,  Hitoshi Harada ,  Shuhei Miyazawa ,  Seiichi Kobayashi ,  Kokichi Harada ,  Takayuki Hida ,  Hisashi Shibata ,  Nobuyuki Yasuda ,  Osamu Asano ,  Yoshihiko Kotake

IPC分类号： A61K31/7076 ,  A61K31/522

CPC分类号： A61K31/506 ,  A61K31/519 ,  A61K31/522 ,  A61K31/5377 ,  A61K31/7076 ,  H04B10/112

摘要： The present invention provides a medicament having a gentle but strong defecation-promoting action without causing diarrhea. That is, it provides a defecation-promoting agent comprising a compound having an adenosine A2 receptor antagonism, preferably an adenosine A2b receptor antagonism, or a salt thereof.

摘要翻译： 本发明提供一种具有温和但强烈的排便促进作用而不引起腹泻的药物。 也就是说，它提供了包含具有腺苷A 2受体拮抗作用的化合物，优选腺苷A 2b受体拮抗剂或其盐的排便促进剂。

公开(公告)号：US07189717B2

公开(公告)日：2007-03-13

申请号：US10257091

申请日：2001-04-26

申请人： Masahiro Yasuda ,  Hitoshi Harada ,  Shuhei Miyazawa ,  Seiichi Kobayashi ,  Kokichi Harada ,  Takayuki Hida ,  Hisashi Shibata ,  Nobuyuki Yasuda ,  Osamu Asano ,  Yoshihiko Kotake

发明人： Masahiro Yasuda ,  Hitoshi Harada ,  Shuhei Miyazawa ,  Seiichi Kobayashi ,  Kokichi Harada ,  Takayuki Hida ,  Hisashi Shibata ,  Nobuyuki Yasuda ,  Osamu Asano ,  Yoshihiko Kotake

IPC分类号： A61K31/506

CPC分类号： A61K31/506 ,  A61K31/519 ,  A61K31/522 ,  A61K31/5377 ,  A61K31/7076 ,  H04B10/112

摘要： The present invention provides a medicament having a gentle but strong defecation-promoting action without causing diarrhea. That is, it provides a defecation-promoting agent comprising a compound having an adenosine A2 receptor antagonism, preferably an adenosine A2b receptor antagonism, or a salt thereof.

摘要翻译： 本发明提供一种具有温和但强烈的排便促进作用而不引起腹泻的药物。 也就是说，它提供了包含具有腺苷A 2受体拮抗作用的化合物，优选腺苷A 2b受体拮抗剂或其盐的排便促进剂。

公开(公告)号：US20060270674A1

公开(公告)日：2006-11-30

申请号：US11500903

申请日：2006-08-09

申请人： Masahiro Yasuda ,  Hitoshi Harada ,  Shuhei Miyazawa ,  Seiichi Kobayashi ,  Kokichi Harada ,  Takayuki Hida ,  Hisashi Shibata ,  Nobuyuki Yasuda ,  Osamu Asano ,  Yoshihiko Kotake

发明人： Masahiro Yasuda ,  Hitoshi Harada ,  Shuhei Miyazawa ,  Seiichi Kobayashi ,  Kokichi Harada ,  Takayuki Hida ,  Hisashi Shibata ,  Nobuyuki Yasuda ,  Osamu Asano ,  Yoshihiko Kotake

IPC分类号： A61K31/5377 ,  A61K31/506 ,  C07D413/14 ,  C07D403/14

CPC分类号： A61K31/506 ,  A61K31/519 ,  A61K31/522 ,  A61K31/5377 ,  A61K31/7076 ,  H04B10/112

摘要： The present invention provides a medicament having a gentle but strong defecation-promoting action without causing diarrhea. That is, it provides a defecation-promoting agent comprising a compound having an adenosine A2receptor antagonism, preferably an adenosine A2b receptor antagonism, or a salt thereof.

摘要翻译： 本发明提供一种具有温和但强烈的排便促进作用而不引起腹泻的药物。 也就是说，它提供了包含具有腺苷A 2受体拮抗作用的化合物，优选腺苷A 2b受体拮抗剂或其盐的排便促进剂。

公开(公告)号：US20090227795A1

公开(公告)日：2009-09-10

申请号：US12375516

申请日：2007-08-02

申请人： Yoshihiko Kotake ,  Koji Sagane ,  Takashi Owa ,  Yoshiharu Mizui ,  Hajime Shimizu ,  Yuko Kiyosue

发明人： Yoshihiko Kotake ,  Koji Sagane ,  Takashi Owa ,  Yoshiharu Mizui ,  Hajime Shimizu ,  Yuko Kiyosue

IPC分类号： C07D405/14 ,  G01N33/566 ,  C07D409/14 ,  C07F5/02 ,  C07D407/06 ,  A61P35/00

CPC分类号： A61K31/365 ,  A61K31/496 ,  C07D407/04 ,  C07D495/04 ,  G01N33/6875 ,  G01N2500/04

摘要： A method of measuring the binding activity of a test compound to a splicing factor 3b (SF3b), which comprises the following steps of: (a) contacting a labeled pladienolide compound and a test compound with a cell or a cell fraction; and (b) measuring the distribution of the bound labeled compound. The method enables to screen for a novel active compound capable of acting on (binding to) a pladienolide target molecule or the like.

摘要翻译： 测试化合物与剪接因子3b（SF3b）的结合活性的方法，其包括以下步骤：（a）使标记的普拉二烯内酯化合物和测试化合物与细胞或细胞级分接触; 和（b）测量结合的标记化合物的分布。 该方法能够筛选能够作用于（结合）扁桃苷内酯靶分子等的新型活性化合物。

公开(公告)号：US07256178B2

公开(公告)日：2007-08-14

申请号：US10522731

申请日：2003-07-31

申请人： Yoshihiko Kotake ,  Jun Niijima ,  Yoshio Fukuda ,  Mitsuo Nagai ,  Regina Mikie Kanada ,  Susumu Takeda ,  Takashi Nakashima ,  Masashi Yoshida ,  Toshio Tsuchida ,  Tomohiro Sameshima

发明人： Yoshihiko Kotake ,  Jun Niijima ,  Yoshio Fukuda ,  Mitsuo Nagai ,  Regina Mikie Kanada ,  Susumu Takeda ,  Takashi Nakashima ,  Masashi Yoshida ,  Toshio Tsuchida ,  Tomohiro Sameshima

IPC分类号： A01N43/04 ,  A61K31/70 ,  A61K39/00 ,  A61K39/38 ,  A61K39/40

CPC分类号： C07D407/06 ,  C07D313/00 ,  C12P17/08 ,  C12P17/16 ,  C12P17/162

摘要： Compounds represented by the following general formula (I), pharmacologically acceptable salts thereof or hydrates of the same: (I) wherein W represents and R3, R7, R16, R17, R20, R21 and R21′ are the same or different and each represents hydrogen, etc. Because of inhibiting angiogenesis and inhibiting the production of VEGF particularly in hypoxia, the compounds (I) are useful as remedies for solid cancer.

摘要翻译： 由以下通式（I）表示的化合物，其药学上可接受的盐或其水合物：其中W表示和R 3，R 7，R 7， SUP> 16，R 17，R 20，R 21和R 21'是 相同或不同，各自表示氢等。由于抑制血管生成并抑制VEGF的产生，特别是在缺氧中，化合物（I）可用作固体癌症的补救措施。

公开(公告)号：US5688800A

公开(公告)日：1997-11-18

申请号：US413100

申请日：1995-03-29

申请人： Hiroaki Nomura ,  Toru Haneda ,  Yoshihiko Kotake ,  Norihiro Ueda ,  Kyosuke Kitoh

发明人： Hiroaki Nomura ,  Toru Haneda ,  Yoshihiko Kotake ,  Norihiro Ueda ,  Kyosuke Kitoh

IPC分类号： C07D239/70 ,  C07D487/04 ,  A61K31/505

CPC分类号： C07D487/04 ,  C07D239/70

摘要： A novel pyrimidine derivative having an excellent antitumor activity, which is represented by the following general formula (I) or a pharmacologically acceptable salt thereof: ##STR1## wherein R.sup.1 represents a hydroxyl or amino group; R.sup.2 represents a phenylene, pyridinediyl, thiendiyl furandiyl or thlazoldiyl group --CO.sub.2 R.sup.5 and --CO.sub.2 R.sup.6 may be the same or different from each other and each represents a carboxyl group or a carboxylic acid ester, the part ##STR2## A represents an oxygen atom, a group represented by the formula: ##STR3## (wherein R.sup.3 and R.sup.4 may be the same or different from each other and each represents a hydrogen or halogen atom or a hydrocarbon group which may be substituted, or alternatively R.sup.3 and R.sup.4 may be united to form an alkylidene group which may be substituted) or a group represented by the formula: ##STR4## (wherein R.sup.70 represents a hydrogen atom or a hydrocarbon group), and n is an integer of 1 to 3, provided that the compound in which R.sup.1 represents oxygen, and hydrogen is attached to nitrogen at 3-position is included in the above shown definition, a process for preparation the same, and an antitumor drug containing the same.

摘要翻译： 一种具有优异抗肿瘤活性的新型嘧啶衍生物，其由下列通式（I）表示或其药理学上可接受的盐：其中R 1表示羟基或氨基; R2表示亚苯基，吡啶二基，噻二烷基呋喃基或噻唑烷基-CO 2 R 5和-CO 2 R 6可以彼此相同或不同，并且各自表示羧基或羧酸酯，部分 A表示氧 原子，由下式表示的基团：彼此不同且各自表示氢或卤素原子或可被取代的烃基，或者R3和R4可以一起形成可被取代的亚烷基）或 以下式表示的基团：其中R 70表示氢原子或烃基，n为1〜3的整数，条件是其中R1表示氧，氮与氮连接的化合物为3 位置包括在上述定义中，其制备方法和含有该定义的抗肿瘤药物。