公开(公告)号：WO2010111634A3

公开(公告)日：2010-09-30

申请号：PCT/US2010/028890

申请日：2010-03-26

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  BROWN, Jason, W. ,  KEUNG, Walter ,  LI, Zhe ,  TYHONAS, John

Inventor： BROWN, Jason, W. ,  KEUNG, Walter ,  LI, Zhe ,  TYHONAS, John

IPC: C07D401/04 ,  C07D401/14 ,  C07D417/06 ,  C07D417/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  A61K31/454 ,  A61P9/10 ,  A61P9/12 ,  A61P35/00

Abstract: The invention relates to compounds having the formula: wherein the variables are as defined herein. The invention further relates to methods of making and using these compounds, intermediates which can be used to make the compounds, and pharmaceutical compositions, kits and articles of manufacture which contain the compounds.

公开(公告)号：WO2010104194A1

公开(公告)日：2010-09-16

申请号：PCT/JP2010/054286

申请日：2010-03-09

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  TSUKAMOTO, Tetsuya ,  WAKABAYASHI, Takeshi ,  OHRA, Taiichi

Inventor： TSUKAMOTO, Tetsuya ,  WAKABAYASHI, Takeshi ,  OHRA, Taiichi

IPC: C07D307/79 ,  C07D307/80 ,  C07D307/81 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/04 ,  C07D407/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12 ,  C07D493/10 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/551

CPC classification number: C07D307/79 ,  C07D307/80 ,  C07D307/81 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/04 ,  C07D407/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12 ,  C07D493/10

Abstract: The present invention provides a compound represented by the following formula (I): wherein: Ring A represents an optionally substituted piperazine ring, an optionally substituted morpholine ring, or an optionally substituted bomopiperazine ring; R 1 and R 2 are the same or different from each other, and represent a hydrogen atom or optionally substituted lower alkyl; R 3 and R 4 are the same or different from each other, and represent a hydrogen atom or halogenated or non-halogenated lower alkyl; R 3 to R 7 are the same or different from each other, and represent a hydrogen atom, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted cycIoaJkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic ring, optionally substituted amino, or acyl; and represents a single bond or double bond, wherein R 2 and R 3 do not exist when carbon atoms respectively adjacent to R 2 : and R 3 form a double bond, and there is no case where all of R 1 to R 7 are hydrogen atoms, and R 1 and R 2 ; may form a ring together with an adjacent carbon atom; or a salt thereof.

Abstract translation: 本发明提供由下式（I）表示的化合物：其中：环A表示任选取代的哌嗪环，任选取代的吗啉环或任选取代的茂金属环; R1和R2彼此相同或不同，表示氢原子或任选取代的低级烷基; R3和R4彼此相同或不同，表示氢原子或卤代或非卤代低级烷基; R 3至R 7彼此相同或不同，并且表示氢原子，羟基，任选取代的低级烷基，任选取代的低级烯基，任选取代的低级烷氧基，任选取代的环烷基，任选取代的芳基，任选取代的芳族杂环， 任选取代的氨基或酰基; 并且表示单键或双键，其中当分别相邻于R2：和R3的碳原子形成双键时，R2和R3不存在，并且不存在所有R 1至R 7都是氢原子的情况，并且R 1和R 2 ; 可与邻近的碳原子一起形成环; 或其盐。

公开(公告)号：WO2010090716A1

公开(公告)日：2010-08-12

申请号：PCT/US2010/000234

申请日：2010-01-28

Applicant: MILLENNIUM PHARMACEUTICALS, INC. ,  TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  BANNO, Hiroshi ,  HIROSE, Masaaki ,  KURASAWA, Osamu ,  LANGSTON, Steven, P. ,  MIZUTANI, Hirotake ,  SHI, Zhan ,  VISIERS, Irache ,  VOS, Tricia, J. ,  VYSKOCIL, Stepan

Inventor： BANNO, Hiroshi ,  HIROSE, Masaaki ,  KURASAWA, Osamu ,  LANGSTON, Steven, P. ,  MIZUTANI, Hirotake ,  SHI, Zhan ,  VISIERS, Irache ,  VOS, Tricia, J. ,  VYSKOCIL, Stepan

IPC: C07D417/04 ,  C07D419/14 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  A61K31/404 ,  A61P29/00

CPC classification number: C07D487/04 ,  C07D417/04 ,  C07D419/14 ,  C07D471/04 ,  C07D513/04

Abstract: This invention provides compounds of formula (IA) or (IB): wherein R 1 , R 2 , G 1 and HY are as described in the specification. The compounds are inhibitors of PI3K and/or mTor and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

Abstract translation: 本发明提供式（IA）或（IB）的化合物：其中R1，R2，G1和HY如说明书中所述。 化合物是PI3K和/或mTor的抑制剂，因此可用于治疗增殖性，炎性或心血管疾病。

公开(公告)号：WO2010064722A1

公开(公告)日：2010-06-10

申请号：PCT/JP2009/070447

申请日：2009-12-01

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  OKANIWA, Masanori ,  TAKAGI, Terufumi

Inventor： OKANIWA, Masanori ,  TAKAGI, Terufumi

IPC: C07D277/82 ,  C07D417/12 ,  A61K31/428 ,  A61K31/496 ,  A61P35/00

CPC classification number: C07D277/82 ,  C07D417/12

Abstract: Provided is a fused heterocycle derivative showing a strong Raf inhibitory activity. A compound represented by the formula (I) wherein each symbol is as defined in the present specification, or a salt thereof.

Abstract translation: 提供显示出强的Raf抑制活性的稠合杂环衍生物。 由式（I）表示的化合物，其中每个符号如本说明书中所定义，或其盐。

公开(公告)号：WO2009154300A2

公开(公告)日：2009-12-23

申请号：PCT/JP2009/061438

申请日：2009-06-17

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  KUROITA, Takanobu ,  IMAEDA, Yasuhiro ,  IWANAGA, Kouichi ,  TAYA, Naohiro ,  TOKUHARA, Hidekazu ,  FUKASE, Yoshiyuki

Inventor： KUROITA, Takanobu ,  IMAEDA, Yasuhiro ,  IWANAGA, Kouichi ,  TAYA, Naohiro ,  TOKUHARA, Hidekazu ,  FUKASE, Yoshiyuki

CPC classification number: C07D401/12 ,  C07D233/90 ,  C07D401/14 ,  C07D405/14 ,  C07D407/12 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D453/02 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D495/04

Abstract: Compounds represented by the formulas (I) (II) wherein each symbol is as defined in the specification, and a prodrug thereof have a superior renin inhibitory activity, and are useful as agents for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension and the like.

Abstract translation: 由式（I）（II）表示的化合物，其中各符号如说明书中所定义，其前药具有优异的肾素抑制活性，可用作预防或治疗高血压的药剂，可归因于 高血压等。

公开(公告)号：WO2009123986A1

公开(公告)日：2009-10-08

申请号：PCT/US2009/038840

申请日：2009-03-30

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  CHANG, Edcon ,  DUONG, Tracy ,  HIRANO, Takehiro ,  MCNEILL, Matthew, H. ,  TERAO, Yoshito ,  VASSAR, Angie

Inventor： CHANG, Edcon ,  DUONG, Tracy ,  HIRANO, Takehiro ,  MCNEILL, Matthew, H. ,  TERAO, Yoshito ,  VASSAR, Angie

IPC: C07D487/04 ,  A61K31/519 ,  A61P25/28 ,  A61P3/00 ,  A61P9/00 ,  A61P29/00 ,  A61P35/00

CPC classification number: C07D487/04 ,  A61K31/519

Abstract: The present invention relates to apoptosis signal-regulating kinase 1 ("ASK1") inhibiting compounds of the formula (I); wherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

Abstract translation: 本发明涉及抑制式（I）化合物的凋亡信号调节激酶1（“ASK1”）; 其中变量如本文所定义。 本发明还涉及包含这些化合物的药物组合物，试剂盒和制品; 用于制备化合物的方法和中间体; 以及使用所述化合物的方法。

公开(公告)号：WO2009107877A1

公开(公告)日：2009-09-03

申请号：PCT/JP2009/054237

申请日：2009-02-27

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  FUTO, Tomomichi ,  NAKAI, Shinichiro ,  DE JONG, Rinaldo Laurentius ,  LEE, Bumsup ,  CHRISTOPHER, Ronald Joseph

Inventor： FUTO, Tomomichi ,  NAKAI, Shinichiro ,  DE JONG, Rinaldo Laurentius ,  LEE, Bumsup ,  CHRISTOPHER, Ronald Joseph

IPC: A61K31/437 ,  A61K31/724 ,  A61K47/48 ,  A61P31/00

CPC classification number: B82Y5/00 ,  A61K9/0019 ,  A61K31/437 ,  A61K31/724 ,  A61K47/6951 ,  A61K2300/00

Abstract: The present invention provides a pharmaceutical composition, wherein solubility and stability of a water-insoluble or slightly water-soluble compound represented by formula (I): wherein each symbol is as defined in the specification, are improved, by combination of the above-mentioned compound and a cyclodextrin derivative and a method for improving solubility, stability and the like of the above-mentioned compound.

Abstract translation: 本发明提供了一种药物组合物，其中通过式（I）表示的水不溶性或微溶于水的化合物的溶解度和稳定性：其中每个符号如说明书中所定义，通过上述 化合物和环糊精衍生物以及提高上述化合物的溶解性，稳定性等的方法。

公开(公告)号：WO2009064675A1

公开(公告)日：2009-05-22

申请号：PCT/US2008/082846

申请日：2008-11-07

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  ADAMS, Mark E. ,  DONG, Qing ,  KALDOR, Stephen W. ,  KANOUNI, Toufike ,  SCORAH, Nicholas ,  WALLACE, Michael B.

Inventor： ADAMS, Mark E. ,  DONG, Qing ,  KALDOR, Stephen W. ,  KANOUNI, Toufike ,  SCORAH, Nicholas ,  WALLACE, Michael B.

IPC: C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  A61K31/4353 ,  A61P35/00

CPC classification number: C07D471/04 ,  C07D498/04 ,  C07D513/04

Abstract: Compounds of the following Formula (I) are provided for use with MEK: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

Abstract translation: 提供下式（I）的化合物与MEK一起使用：其中变量如本文所定义。 还提供了包含这些化合物的药物组合物，试剂盒和制品; 用于制备化合物的方法和中间体; 以及使用所述化合物的方法。

公开(公告)号：WO2008115890A2

公开(公告)日：2008-09-25

申请号：PCT/US2008/057276

申请日：2008-03-17

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  DONG, Qing ,  KANOUNI, Toufike ,  WALLACE, Michael B.

Inventor： DONG, Qing ,  KANOUNI, Toufike ,  WALLACE, Michael B.

CPC classification number: C07D215/56 ,  C07D215/38 ,  C07D401/12 ,  C07D471/04 ,  C07D491/052

Abstract: Compounds are provided for use with MEK that comprise: formula (I) wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

Abstract translation: 提供了与MEK一起使用的化合物，其包含：式（I），其中变量如本文所定义。 还提供了包含这些化合物的药物组合物，试剂盒和制品; 用于制备化合物的方法和中间体; 以及使用所述化合物的方法。

公开(公告)号：WO2008114800A2

公开(公告)日：2008-09-25

申请号：PCT/JP2008/055016

申请日：2008-03-12

Applicant: TAKEDA PHARMACEUTICAL COMPANY LIMITED ,  MURAKAWA, Yusuke ,  HOHOKABE, Miyuki

Inventor： MURAKAWA, Yusuke ,  HOHOKABE, Miyuki

IPC: A61K9/16 ,  A61K31/513

CPC classification number: A61K9/2018 ,  A61K9/2054 ,  A61K9/2059 ,  A61K31/513

Abstract: The present invention provides a solid preparation containing 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-4-fluorobenzonitrile (compound (A)) or a salt thereof as a pharmaceutically active ingredient. Specifically, the present invention provides a solid preparation containing a granule composed of compound (A) or a salt thereof and an additive (excluding microcrystalline cellulose) and a tablet containing (a) a granule containing compound (A) or a salt thereof and microcrystalline cellulose, and (b) a tableting aid containing magnesium stearate and microcrystalline cellulose.

Abstract translation: 本发明提供含有2 - [[6 - [（3R）-3-氨基-1-哌啶基] -3,4-二氢-3-甲基-2,4-二氧代-1（2H） - 嘧啶基 ]甲基] -4-氟苄腈（化合物（A））或其盐作为药物活性成分。 具体地说，本发明提供一种固体制剂，其含有由化合物（A）或其盐和添加剂（不包括微晶纤维素）组成的颗粒和含有（a）含有化合物（A）或其盐的颗粒和微晶 纤维素，和（b）含有硬脂酸镁和微晶纤维素的压片助剂。