公开(公告)号：US20090286791A1

公开(公告)日：2009-11-19

申请号：US12309493

申请日：2007-07-20

申请人： Shuji Kitamura ,  Thomas Daniel Aicher ,  Steve Gonzales ,  Yvan Le Huerou ,  Scott Alan Pratt ,  Tim Turner ,  Yoshihisa Nakada

发明人： Shuji Kitamura ,  Thomas Daniel Aicher ,  Steve Gonzales ,  Yvan Le Huerou ,  Scott Alan Pratt ,  Tim Turner ,  Yoshihisa Nakada

IPC分类号： A61K31/4155 ,  C07D401/12 ,  C07D403/12 ,  C07D413/14 ,  C07D231/14 ,  A61P3/04 ,  A61P3/10 ,  A61K31/4439 ,  A61K31/4184 ,  A61K31/498 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/506

CPC分类号： C07D401/12 ,  C07D207/08 ,  C07D213/81 ,  C07D233/90 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/06 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： The present invention provides compounds represented by the formula (Ia): the formula (Ib): the formula (Ic): and the formula (Id): wherein each symbol is as defined in the specification.According to the present invention, these compounds have a DGAT inhibitory activity and are useful for the prophylaxis, treatment or improvement of diseases or pathologies caused by high expression or high activation of DGAT.

摘要翻译： 本发明提供由式（Ia）表示的化合物：式（Ib）：式（Ic）：和式（Id）：其中每个符号如说明书中所定义。 根据本发明，这些化合物具有DGAT抑制活性，可用于预防，治疗或改善由高表达或高活化DGAT引起的疾病或病理。

公开(公告)号：US20120065196A1

公开(公告)日：2012-03-15

申请号：US12309480

申请日：2007-07-20

申请人： Shuji Kitamura ,  Thomas Daniel Aicher ,  Steve Gonzales ,  Yvan Le Huerou ,  Scott Alan Pratt ,  Yoshihisa Nakada

发明人： Shuji Kitamura ,  Thomas Daniel Aicher ,  Steve Gonzales ,  Yvan Le Huerou ,  Scott Alan Pratt ,  Yoshihisa Nakada

IPC分类号： A61K31/541 ,  A61K31/454 ,  A61K31/445 ,  C07D401/12 ,  C07D413/12 ,  A61K31/4245 ,  C07D513/00 ,  A61K31/428 ,  A61K31/497 ,  C07D403/12 ,  A61K31/5377 ,  C07D417/12 ,  A61P3/04 ,  A61P3/10 ,  A61P3/06 ,  C07D401/06

CPC分类号： C07D401/12 ,  C07D231/14 ,  C07D231/56 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08

摘要： The present invention provides compounds represented by the formula (Ie): and the formula (If): wherein each symbol is as defined in the specification.According to the present invention, these compounds have a DGAT inhibitory activity and are useful for the prophylaxis, treatment or improvement of diseases or pathologies caused by high expression or high activation of DGAT.

摘要翻译： 本发明提供由式（Ie）表示的化合物：和式（If）：其中每个符号如说明书中所定义。 根据本发明，这些化合物具有DGAT抑制活性，可用于预防，治疗或改善由高表达或高活化DGAT引起的疾病或病理。

公开(公告)号：US07214673B2

公开(公告)日：2007-05-08

申请号：US10505805

申请日：2003-03-17

申请人： Thomas Daniel Aicher ,  Zhaogen Chen ,  Joseph Herman Krushinski, Jr. ,  Yvan Le Huerou ,  Marta Maria Pineiro-Nunez ,  Kevin Michael Ruley ,  John Mehnert Schaus ,  Dennis Charles Thompson ,  David Edward Tupper ,  Ying Chen ,  Margaret Mary Faul ,  Vincent Patrick Rocco

发明人： Thomas Daniel Aicher ,  Zhaogen Chen ,  Joseph Herman Krushinski, Jr. ,  Yvan Le Huerou ,  Marta Maria Pineiro-Nunez ,  Kevin Michael Ruley ,  John Mehnert Schaus ,  Dennis Charles Thompson ,  David Edward Tupper ,  Ying Chen ,  Margaret Mary Faul ,  Vincent Patrick Rocco

IPC分类号： A61P25/00 ,  A61K31/55 ,  C07D243/10

CPC分类号： C07D487/04 ,  C07D243/38 ,  C07D495/04 ,  C07D513/04

摘要： Described herein are antipyschotic compounds of formula (I) wherein, A is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; Alk is (C1-4) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; R1 is hydrogen or (C1-4) alkyl optionally substituted with OH, OR3, or OCH2CH2OH, wherein R3 is (C1-2) alkyl; R2 is H, (C1-6) alkyl, halogen, fluorinated (C1-6) alkyl, OR4, SR4, NO2, CN, COR4, CONR5R6, SO2NR5R6, NR5R6, NR5COR4, NR5SO2R4, or optionally substituted phenyl, wherein R4 is hydrogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, or optionally substituted phenyl, R5 and R6 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, OR7, SR7, NO2, CN, COR7, CONR8R9, SO2NR8R9, NR8SO2R7, NR8R9, or optionally substituted phenyl, wherein R7 is hydrogen, (C1-6) alkyl, fluorinated alkyl, or optionally substituted phenyl, R8 and R9 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorder, and pharmaceutical formulations of the compounds of formula (I).

公开(公告)号：US08841304B2

公开(公告)日：2014-09-23

申请号：US12812447

申请日：2009-01-08

申请人： James F. Blake ,  Indrani W. Gunawardana ,  Yvan Le Huerou ,  Peter J. Mohr ,  Eli M. Wallace ,  Bin Wang

发明人： James F. Blake ,  Indrani W. Gunawardana ,  Yvan Le Huerou ,  Peter J. Mohr ,  Eli M. Wallace ,  Bin Wang

IPC分类号： C07D471/04 ,  A61K31/496

CPC分类号： C07D471/04

摘要： Compounds of Formula (I) are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula (I) and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

摘要翻译： 式（I）的化合物可用于抑制CHK1和/或CHK2。 公开了使用式（I）化合物及其立体异构体及其药学上可接受的盐在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US20120178715A1

公开(公告)日：2012-07-12

申请号：US13393767

申请日：2010-09-03

申请人： Steven W. Andrews ,  Kevin Ronald Condroski ,  Lisa A. De Meese ,  Jay Bradford Fell ,  John P. Fischer ,  John A. Josey ,  Kevin Koch ,  Yvan Le Huerou ,  Gregory F. Miknis ,  Martha E. Rodriguez ,  George T. Topalov ,  Eli M. Wallace ,  Rui Xu

发明人： Steven W. Andrews ,  Kevin Ronald Condroski ,  Lisa A. De Meese ,  Jay Bradford Fell ,  John P. Fischer ,  John A. Josey ,  Kevin Koch ,  Yvan Le Huerou ,  Gregory F. Miknis ,  Martha E. Rodriguez ,  George T. Topalov ,  Eli M. Wallace ,  Rui Xu

IPC分类号： A61K31/519 ,  A61K31/5377 ,  A61P35/00 ,  A61K31/5386 ,  A61K31/675 ,  C07D487/04 ,  C07D498/08

CPC分类号： C07D487/04

摘要： Compounds of Formula I: and salts thereof in which R1, R2, R2a, R3, n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.

摘要翻译： 式I化合物及其盐，其中R 1，R 2，R 2a，R 3，n，X和环B具有本说明书中给出的含义，是mTOR的抑制剂，可用于治疗对抑制作用敏感的疾病 mTOR，如癌症。

公开(公告)号：US20090209554A1

公开(公告)日：2009-08-20

申请号：US10593910

申请日：2005-03-23

申请人： Steven A. Boyd ,  Kevin R. Condroski ,  Jason De Meese ,  Stephen S. Gonzales ,  Indrani W. Gunawardana ,  Tomas Kaplan ,  Yvan Le Huerou ,  Joseph Lyssikatos ,  Todd T. Romoff ,  Francis X. Sullivan ,  Allen Thomas

发明人： Steven A. Boyd ,  Kevin R. Condroski ,  Jason De Meese ,  Stephen S. Gonzales ,  Indrani W. Gunawardana ,  Tomas Kaplan ,  Yvan Le Huerou ,  Joseph Lyssikatos ,  Todd T. Romoff ,  Francis X. Sullivan ,  Allen Thomas

IPC分类号： A61K31/497 ,  C12N9/99 ,  C12N5/06 ,  A61K31/4439 ,  A61P35/00 ,  C07D417/06

CPC分类号： C07D417/06 ,  C07D417/14

摘要： The present invention provides N-3′-pyridyl-methyl or N-2′-pyrazinylmethyl thiazolium derivatives of formula (I) which are useful as transketolase inhibitors wherein R1, R2, R3, Y, R5-R9, Ra-Rd, n and X− are as defined herein. The present invention also provides pharmaceutical compositions comprising the compounds of formula (I). The invention provides methods for inhibiting transketolase activity, reducing cellular ribose-5-phosphate levels, inhibiting nucleic acid synthesis, inhibiting cell proliferation and tumor cell growth in vitro and in vivo, stimulating apoptosis in tumor cells and treating cancer by administering a compound of formula (I) or a pharmaceutical composition thereof.

摘要翻译： 本发明提供了可用作转酮酶抑制剂的式（I）的N-3'-吡啶基 - 甲基或N-2'-吡嗪基甲基噻唑鎓衍生物，其中R1，R2，R3，Y，R5-R9，Ra-Rd，n 和X-如本文所定义。 本发明还提供包含式（I）化合物的药物组合物。 本发明提供了抑制转酮醇酶活性，减少细胞核糖-5-磷酸水平，抑制核酸合成，抑制体外和体内细胞增殖和肿瘤细胞生长，刺激肿瘤细胞凋亡和通过给予式 （I）化合物或其药物组合物。

公开(公告)号：US08545897B2

公开(公告)日：2013-10-01

申请号：US13425186

申请日：2012-03-20

申请人： Yvan Le Huerou ,  James F. Blake ,  Indrani W. Gunwardana ,  Pete Mohr ,  Eli M. Wallace ,  Bin Wang ,  Mark Joseph Chicarelli ,  Michael Lyon

发明人： Yvan Le Huerou ,  James F. Blake ,  Indrani W. Gunwardana ,  Pete Mohr ,  Eli M. Wallace ,  Bin Wang ,  Mark Joseph Chicarelli ,  Michael Lyon

IPC分类号： A61K31/4545 ,  A61K31/437 ,  A61K31/497 ,  A61K31/506 ,  A61K33/24 ,  A61K31/513 ,  A61K31/444 ,  A61K31/501 ,  A61P35/00

CPC分类号： C07D471/04 ,  C07D401/06 ,  C07D519/00

摘要： Compounds of Formula I are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

公开(公告)号：US08372842B2

公开(公告)日：2013-02-12

申请号：US12812448

申请日：2009-01-08

申请人： James F. Blake ,  Indrani W. Gunawardana ,  Yvan Le Huerou ,  Peter J. Mohr ,  Eli M. Wallace ,  Bin Wang

发明人： James F. Blake ,  Indrani W. Gunawardana ,  Yvan Le Huerou ,  Peter J. Mohr ,  Eli M. Wallace ,  Bin Wang

IPC分类号： A61K31/496 ,  C07D471/04

CPC分类号： C07D471/04

摘要： Compounds of Formula I are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

摘要翻译： 式I的化合物可用于抑制CHK1和/或CHK2。 公开了使用式I化合物及其立体异构体及其药学上可接受的盐在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US07879885B2

公开(公告)日：2011-02-01

申请号：US10593911

申请日：2005-03-23

申请人： Steven A. Boyd ,  Kevin R. Condroski ,  Allen Thomas ,  Stephen S. Gonzales ,  Indrani W. Gunawardana ,  Yvan Le Huerou ,  Todd T. Romoff ,  Francis X. Sullivan

发明人： Steven A. Boyd ,  Kevin R. Condroski ,  Allen Thomas ,  Stephen S. Gonzales ,  Indrani W. Gunawardana ,  Yvan Le Huerou ,  Todd T. Romoff ,  Francis X. Sullivan

IPC分类号： A61K31/44

CPC分类号： C07D213/73 ,  C07D405/12 ,  C07D411/12

摘要： The present invention provides thioalkeneamides of formula (I) which are useful as transketolase inhibitors: wherein R1, R2, R3, R4, R5, R6, Ra-Rd, n and ring A are as defined herein. The present invention also provides pharmaceutical compositions comprising the compounds of formula (I). The invention provides methods for inhibiting transketolase activity, reducing cellular ribose-5-phosphate levels, inhibiting nucleic acid synthesis, inhibiting cell proliferation and tumor cell growth in vitro and in vivo, stimulating apoptosis in tumor cells and treating cancer by administering a compound of formula (I) or a pharmaceutical composition thereof.

摘要翻译： 本发明提供了可用作转酮酶抑制剂的式（I）的硫代链烯酰胺：其中R1，R2，R3，R4，R5，R6，Ra-Rd，n和环A如本文所定义。 本发明还提供包含式（I）化合物的药物组合物。 本发明提供了抑制转酮醇酶活性，减少细胞核糖-5-磷酸水平，抑制核酸合成，抑制体外和体内细胞增殖和肿瘤细胞生长，刺激肿瘤细胞凋亡和通过给予式 （I）化合物或其药物组合物。

公开(公告)号：US08865726B2

公开(公告)日：2014-10-21

申请号：US13393767

申请日：2010-09-03

申请人： Steven W. Andrews ,  Kevin Ronald Condroski ,  Lisa A. De Meese ,  Jay Bradford Fell ,  John P. Fischer ,  John A. Josey ,  Kevin Koch ,  Yvan Le Huerou ,  Gregory F. Miknis ,  Martha E. Rodriguez ,  George T. Topalov ,  Eli M. Wallace ,  Rui Xu

发明人： Steven W. Andrews ,  Kevin Ronald Condroski ,  Lisa A. De Meese ,  Jay Bradford Fell ,  John P. Fischer ,  John A. Josey ,  Kevin Koch ,  Yvan Le Huerou ,  Gregory F. Miknis ,  Martha E. Rodriguez ,  George T. Topalov ,  Eli M. Wallace ,  Rui Xu

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P35/00

CPC分类号： C07D487/04

摘要： Compounds of Formula I: and salts thereof in which R1, R2, R2a, R3, n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.

摘要翻译： 式I化合物及其盐，其中R 1，R 2，R 2a，R 3，n，X和环B具有本说明书中给出的含义，是mTOR的抑制剂，可用于治疗对抑制作用敏感的疾病 mTOR，如癌症。