公开(公告)号：US07279469B2

公开(公告)日：2007-10-09

申请号：US10715111

申请日：2003-11-17

申请人： Albert C. Pierce ,  Michael Amost ,  Robert J. Davies ,  Cornelia J. Forster ,  Vincent Galullo ,  Ronald Grey, Jr. ,  Mark Ledeboer ,  Shi-Kai Tian ,  Jinwang Xu ,  Hayley Binch ,  Brian Ledford ,  David Messersmith ,  Suganthi Nanthakumar ,  Andrew Jayaraj ,  Greg Henkel ,  Francesco G. Salituro ,  Jian Wang

发明人： Albert C. Pierce ,  Michael Amost ,  Robert J. Davies ,  Cornelia J. Forster ,  Vincent Galullo ,  Ronald Grey, Jr. ,  Mark Ledeboer ,  Shi-Kai Tian ,  Jinwang Xu ,  Hayley Binch ,  Brian Ledford ,  David Messersmith ,  Suganthi Nanthakumar ,  Andrew Jayaraj ,  Greg Henkel ,  Francesco G. Salituro ,  Jian Wang

IPC分类号： A61K31/541 ,  A61K31/55 ,  A61K31/4196 ,  A61K31/5377 ,  C07D417/02 ,  C07D413/02

CPC分类号： C07D401/04 ,  C07D249/10 ,  C07D249/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/14 ,  C07D487/04 ,  C07D495/04

摘要： The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及蛋白激酶抑制剂。 本发明还提供包含本发明化合物的药物组合物和使用该组合物治疗各种疾病的方法。

公开(公告)号：US07902239B2

公开(公告)日：2011-03-08

申请号：US11774702

申请日：2007-07-09

申请人： Albert C. Pierce ,  Michael Arnost ,  Robert J. Davies ,  Cornelia J. Forster ,  Vincent Galullo ,  Ronald Grey, Jr. ,  Mark Ledeboer ,  Shi-Kai Tian ,  Jinwang Xu ,  Hayley Binch ,  Brian Ledford ,  David Messersmith ,  Suganthi Nanthakumar ,  Andrew Jayaraj ,  Greg Henkel ,  Francesco G. Salituro ,  Jian Wang

发明人： Albert C. Pierce ,  Michael Arnost ,  Robert J. Davies ,  Cornelia J. Forster ,  Vincent Galullo ,  Ronald Grey, Jr. ,  Mark Ledeboer ,  Shi-Kai Tian ,  Jinwang Xu ,  Hayley Binch ,  Brian Ledford ,  David Messersmith ,  Suganthi Nanthakumar ,  Andrew Jayaraj ,  Greg Henkel ,  Francesco G. Salituro ,  Jian Wang

IPC分类号： A61K31/541 ,  A61K31/55 ,  A61K31/4196 ,  A61K31/5377

CPC分类号： C07D401/04 ,  C07D249/10 ,  C07D249/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/14 ,  C07D487/04 ,  C07D495/04

摘要： The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及蛋白激酶抑制剂。 本发明还提供包含本发明化合物的药物组合物和使用该组合物治疗各种疾病的方法。

公开(公告)号：US07598245B2

公开(公告)日：2009-10-06

申请号：US11787165

申请日：2007-04-13

申请人： Michael J. Arnost ,  Guy W. Bemis ,  Robert J. Davies ,  Cornelia J. Forster ,  Ronald Grey, Jr. ,  Mark W. Ledeboer ,  Brian Ledford ,  Craig Marhefka ,  David Messersmith ,  Albert C. Pierce ,  Francesco G. Salituro ,  Jian Wang

发明人： Michael J. Arnost ,  Guy W. Bemis ,  Robert J. Davies ,  Cornelia J. Forster ,  Ronald Grey, Jr. ,  Mark W. Ledeboer ,  Brian Ledford ,  Craig Marhefka ,  David Messersmith ,  Albert C. Pierce ,  Francesco G. Salituro ,  Jian Wang

IPC分类号： A61K31/427 ,  A61K31/5377 ,  C07D413/12 ,  C07D263/32 ,  C07D249/08

CPC分类号： C07D401/04 ,  C07D249/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/04

摘要： The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention, processes for preparing the compounds and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及蛋白激酶抑制剂。 本发明还提供包含本发明化合物的药物组合物，制备化合物的方法和使用该组合物治疗各种疾病的方法。

公开(公告)号：US07226920B2

公开(公告)日：2007-06-05

申请号：US10914051

申请日：2004-08-06

申请人： Michael J. Arnost ,  Guy W. Bemis ,  Robert J. Davies ,  Cornelia J. Forster ,  Ronald Grey, Jr. ,  Mark W. Ledeboer ,  Brian Ledford ,  Craig Marhefka ,  David Messersmith ,  Albert C. Pierce ,  Francesco G. Salituro ,  Jian Wang

发明人： Michael J. Arnost ,  Guy W. Bemis ,  Robert J. Davies ,  Cornelia J. Forster ,  Ronald Grey, Jr. ,  Mark W. Ledeboer ,  Brian Ledford ,  Craig Marhefka ,  David Messersmith ,  Albert C. Pierce ,  Francesco G. Salituro ,  Jian Wang

IPC分类号： A61K31/427 ,  A61K31/5377 ,  C07D413/12 ,  C07D263/32 ,  C07D249/08

CPC分类号： C07D401/04 ,  C07D249/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/04

摘要： The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention, processes for preparing the compounds and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及蛋白激酶抑制剂。 本发明还提供包含本发明化合物的药物组合物，制备化合物的方法和使用该组合物治疗各种疾病的方法。

公开(公告)号：US20050261268A1

公开(公告)日：2005-11-24

申请号：US10914051

申请日：2004-08-06

申请人： Michael J. Arnost ,  Guy W. Bemis ,  Robert J. Davies ,  Cornelia J. Forster ,  Ronald Grey ,  Mark W. Ledeboer ,  Brian Ledford ,  Craig Marhefka ,  David Messersmith ,  Albert C. Pierce ,  Francesco Salituro ,  Jian Wang

发明人： Michael J. Arnost ,  Guy W. Bemis ,  Robert J. Davies ,  Cornelia J. Forster ,  Ronald Grey ,  Mark W. Ledeboer ,  Brian Ledford ,  Craig Marhefka ,  David Messersmith ,  Albert C. Pierce ,  Francesco Salituro ,  Jian Wang

IPC分类号： A61P35/00 ,  C07D249/14 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  A61K31/545 ,  A61K31/4196 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/53 ,  C07D501/14 ,  C07D43/02

CPC分类号： C07D401/04 ,  C07D249/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/04

摘要： The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention, processes for preparing the compounds and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及蛋白激酶抑制剂。 本发明还提供包含本发明化合物的药物组合物，制备化合物的方法和使用该组合物治疗各种疾病的方法。

公开(公告)号：US07691853B2

公开(公告)日：2010-04-06

申请号：US11369220

申请日：2006-03-06

申请人： David Bebbington ,  Hayley Binch ,  Ronald Knegtel ,  Julian M. C. Golec ,  Sanjay Patel ,  Jean-Damien Charrier ,  David Kay ,  Robert J. Davies ,  Pan Li ,  Marion W. Wannamaker ,  Cornelia J. Forster ,  Albert C. Pierce

发明人： David Bebbington ,  Hayley Binch ,  Ronald Knegtel ,  Julian M. C. Golec ,  Sanjay Patel ,  Jean-Damien Charrier ,  David Kay ,  Robert J. Davies ,  Pan Li ,  Marion W. Wannamaker ,  Cornelia J. Forster ,  Albert C. Pierce

IPC分类号： C07D403/12 ,  C07D239/94 ,  A61K31/517 ,  A61K31/506 ,  A61P25/18 ,  A61P25/28

CPC分类号： C07D401/14 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D473/16 ,  C07D487/04 ,  C07D491/04 ,  C07D491/10 ,  C07D493/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04

摘要： This invention describes novel pyrazole compounds of formula IV: wherein Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx and Ry are independently selected from T—R3, or taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 1-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen; and R2, R2′, T, and R3 are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of aurora-2 and GSK-3, for treating diseases such as cancer, diabetes and Alzheimer's disease.

摘要翻译： 本发明描述了式IV的新型吡唑化合物：其中环D是5-7元单环或选自芳基，杂芳基，杂环基或碳环基的8-10元双环; R x和R y独立地选自T-R 3，或与它们的插入原子一起形成具有1-3个选自氧，硫或氮的环杂原子的稠合的，不饱和的或部分不饱和的5-8元环; R2，R2'，T和R3如说明书中所述。 这些化合物可用作蛋白激酶抑制剂，特别是作为用于治疗诸如癌症，糖尿病和阿尔茨海默病的疾病的极光-2和GSK-3的抑制剂。

公开(公告)号：US08691848B2

公开(公告)日：2014-04-08

申请号：US12009829

申请日：2008-01-22

申请人： Marion W. Wannamaker ,  Guy W. Bemis ,  Paul S. Charifson ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  Keith P. Wilson ,  James W. Janetka ,  Robert J. Davies ,  Anne-Laure Grillot ,  Zhan Shi ,  Cornelia J. Forster

发明人： Marion W. Wannamaker ,  Guy W. Bemis ,  Paul S. Charifson ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  Keith P. Wilson ,  James W. Janetka ,  Robert J. Davies ,  Anne-Laure Grillot ,  Zhan Shi ,  Cornelia J. Forster

IPC分类号： C07D405/12 ,  A61K31/443

CPC分类号： C07K5/0202 ,  A61K38/00 ,  C07D401/12 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389 ,  Y02A50/475

摘要： The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1β converting enzyme (“ICE”) inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1-(“IL-1”), apoptosis-, interferon-γ inducing factor-(IGIF), or interferon-γ-(“IFN-γ”) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN-γ production and methods for treating interleukin-1, apoptosis-, and interferon-γ-mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.

摘要翻译： 本发明涉及新型的化合物，其是胱天蛋白酶抑制剂，特别是白细胞介素-1bb; 转化酶（“ICE”）抑制剂。 本发明还涉及包含这些化合物的药物组合物。 本发明的化合物和药物组合物特别适用于抑制胱天蛋白酶活性，因此可有利地用作抗白介素-1-（“IL-1”），细胞凋亡，干扰素-γ诱导因子（IGIF） 或“干扰素-γ”（“IFN-γ”）介导的疾病，包括炎性疾病，自身免疫性疾病，破坏性骨病，增殖性疾病，感染性疾病和退行性疾病。 本发明还涉及使用本发明的化合物和组合物来抑制半胱天冬酶活性和降低IGIF产生和IFN-γ产生的方法以及用于治疗白细胞介素-1，细胞凋亡和干扰素-γ介导的疾病的方法。 本发明还涉及制备本发明化合物的方法。

公开(公告)号：US20090048226A1

公开(公告)日：2009-02-19

申请号：US12009829

申请日：2008-01-22

申请人： Marion W. Wannamaker ,  Guy W. Bemis ,  Paul S. Charifson ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  Keith P. Wilson ,  James W. Janetka ,  Robert J. Davies ,  Anne-Laure Grillot ,  Zhan Shi ,  Cornelia J. Forster

发明人： Marion W. Wannamaker ,  Guy W. Bemis ,  Paul S. Charifson ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  Keith P. Wilson ,  James W. Janetka ,  Robert J. Davies ,  Anne-Laure Grillot ,  Zhan Shi ,  Cornelia J. Forster

IPC分类号： C07C237/02 ,  A61K31/16 ,  A61K31/40 ,  C07D207/00 ,  C07D277/62 ,  A61K31/428 ,  C07D277/02 ,  C07D237/30 ,  A61K31/496 ,  C07D405/14 ,  C07D405/02 ,  A61K31/5377 ,  C07D205/02 ,  A61K31/397 ,  A61K31/497 ,  C07D413/14 ,  C07D403/02 ,  C07D401/02 ,  A61P1/00 ,  A61P35/02 ,  A61P35/00 ,  A61P17/00 ,  A61P31/00 ,  A61P19/00 ,  A61P7/00 ,  A61P25/00 ,  A61P37/00 ,  A61P29/00 ,  A61K31/502 ,  C07D471/04 ,  A61K31/44 ,  A61K31/47 ,  C07D215/16 ,  A61K31/415 ,  C07D231/02

CPC分类号： C07K5/0202 ,  A61K38/00 ,  C07D401/12 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389 ,  Y02A50/475

摘要： The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1β converting enzyme (“ICE”) inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1-(“IL-1”), apoptosis-, interferon-γ inducing factor-(IGIF), or interferon-γ-(“IFN-γ”) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN-γ production and methods for treating interleukin-1, apoptosis-, and interferon-γ-mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.

公开(公告)号：US06531474B1

公开(公告)日：2003-03-11

申请号：US09665503

申请日：2000-09-19

申请人： Marion W. Wannamaker ,  Guy W. Bemis ,  Paul S. Charifson ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  Keith P. Wilson ,  James W. Janetka ,  Robert J. Davies ,  Anne-Laure Grillot ,  Zhan Shi ,  Cornelia J. Forster

发明人： Marion W. Wannamaker ,  Guy W. Bemis ,  Paul S. Charifson ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  Keith P. Wilson ,  James W. Janetka ,  Robert J. Davies ,  Anne-Laure Grillot ,  Zhan Shi ,  Cornelia J. Forster

IPC分类号： C07D20724

CPC分类号： C07K5/0202 ,  A61K38/00 ,  C07D401/12 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389 ,  Y02A50/475

摘要： The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1&bgr; converting enzyme (“ICE”) inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1-(“IL-1”), apoptosis-, interferon-&ggr; inducing factor-(IGIF), or interferon-&ggr;-(“IFN-&ggr;”) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN-&ggr; production and methods for treating interleukin-1, apoptosis-, and interferon-&ggr;-mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.

公开(公告)号：US07491730B2

公开(公告)日：2009-02-17

申请号：US10632340

申请日：2003-08-01

申请人： Cornelia J. Forster ,  Larry C. Park ,  Marion W. Wannamaker ,  Yung-Mae M. Yao

发明人： Cornelia J. Forster ,  Larry C. Park ,  Marion W. Wannamaker ,  Yung-Mae M. Yao

IPC分类号： C07D403/12 ,  C07D403/14 ,  C07D417/14 ,  A61K31/4162 ,  A61K31/506 ,  A61K31/5377 ,  A61P3/10 ,  A61P9/10 ,  A61P25/18

CPC分类号： C07D403/12 ,  C07D471/04

摘要： The present invention provides a compound of formula I: or a pharmaceutically acceptable derivative thereof. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK3 mammalian protein kinase. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.

摘要翻译： 本发明提供式I化合物或其药学上可接受的衍生物。 这些化合物是蛋白激酶的抑制剂，特别是GSK3哺乳动物蛋白激酶的抑制剂。 本发明还提供包含本发明化合物的药学上可接受的组合物和利用这些化合物和组合物治疗各种蛋白激酶介导的病症的方法。