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：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：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：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：US20110015371A1

公开(公告)日：2011-01-20

申请号：US12800046

申请日：2010-05-05

申请人： Guy W. Bemis ,  Julian M. C. Golec ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  David J. Livingston

发明人： Guy W. Bemis ,  Julian M. C. Golec ,  David J. Lauffer ,  Michael D. Mullican ,  Mark A. Murcko ,  David J. Livingston

IPC分类号： C07K5/10 ,  C07D213/76 ,  C07D413/12 ,  C07K5/08 ,  C07D233/90 ,  C07D207/34

CPC分类号： C07D243/08 ,  A61K38/00 ,  C07D243/12 ,  C07D263/56 ,  C07D413/04 ,  C07D487/04 ,  C07K5/0202 ,  C07K5/06052 ,  C07K5/0812

摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

摘要翻译： 本发明涉及作为白介素-1和bgr的抑制剂的新型化合物。 转化酶。 本发明的ICE抑制剂的特征在于具体的结构和物理化学特征。 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ICE活性，因此可有利地用作抗白介素-1介导的疾病（包括炎性疾病，自身免疫性疾病和神经变性疾病）的药物。 本发明还涉及使用本发明的化合物和组合物来抑制ICE活性的方法和用于治疗白细胞介素-1介导的疾病的方法。

公开(公告)号：US06608060B1

公开(公告)日：2003-08-19

申请号：US09336266

申请日：1999-06-14

申请人： Guy W. Bemis ,  Francesco Gerald Salituro ,  John Patrick Duffy ,  John E. Cochran ,  Edmund Martin Harrington ,  Mark A. Murko ,  Keith P. Wilson ,  Michael Su ,  Vincent P. Galullo

发明人： Guy W. Bemis ,  Francesco Gerald Salituro ,  John Patrick Duffy ,  John E. Cochran ,  Edmund Martin Harrington ,  Mark A. Murko ,  Keith P. Wilson ,  Michael Su ,  Vincent P. Galullo

IPC分类号： C07D48704

CPC分类号： C07D213/70 ,  C07D213/56 ,  C07D213/75 ,  C07D237/18 ,  C07D241/12 ,  C07D241/20 ,  C07D401/04 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04 ,  C07D471/04 ,  C07D487/04 ,  C07F9/6561

摘要： The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

公开(公告)号：US06258948B1

公开(公告)日：2001-07-10

申请号：US09400639

申请日：1999-09-21

申请人： Mark James Batchelor ,  David Bebbington ,  Guy W. Bemis ,  Wolf Herman Fridman ,  Roger John Gillespie ,  Julian M. C. Golec ,  Yong Gu ,  David J. Lauffer ,  David J. Livingston ,  Saroop Singh Matharu ,  Michael D. Mullican ,  Mark A. Murcko ,  Robert Murdoch ,  Philip Nyce ,  Andrea L. C. Robidoux ,  Michael Su ,  M. Woods Wannamaker ,  Keith P. Wilson ,  Robert E. Zelle

发明人： Mark James Batchelor ,  David Bebbington ,  Guy W. Bemis ,  Wolf Herman Fridman ,  Roger John Gillespie ,  Julian M. C. Golec ,  Yong Gu ,  David J. Lauffer ,  David J. Livingston ,  Saroop Singh Matharu ,  Michael D. Mullican ,  Mark A. Murcko ,  Robert Murdoch ,  Philip Nyce ,  Andrea L. C. Robidoux ,  Michael Su ,  M. Woods Wannamaker ,  Keith P. Wilson ,  Robert E. Zelle

IPC分类号： C07D26702

CPC分类号： C07D243/12 ,  A61K38/00 ,  C07D401/06 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07K5/0202 ,  C07K5/06139 ,  C07K5/0821

摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-IB converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-&ggr;-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-&ggr;-mediated diseases and decreasing IGIF and IFN-&ggr; production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

摘要翻译： 本发明涉及作为白介素-IB转化酶抑制剂的新型化合物。 本发明的ICE抑制剂的特征在于具体的结构和物理化学特征。 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ICE活性，因此可有利地用作抗IL-1，细胞凋亡，IGIF和IFN-γ介导的疾病，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，退行性疾病和坏死性疾病。 本发明还涉及使用本发明的化合物和组合物来抑制ICE活性，治疗白细胞介素-1，细胞凋亡，IGIF-和IFN-γ介导的疾病以及减少IGIF和IFN-γ产生的方法。 本发明还涉及制备N-酰基氨基化合物的方法。

公开(公告)号：US6008217A

公开(公告)日：1999-12-28

申请号：US575641

申请日：1995-12-20

申请人： Mark James Batchelor ,  David Bebbington ,  Guy W. Bemis ,  Wolf Herman Fridman ,  Roger John Gillespie ,  Julian M. C. Golec ,  David J. Lauffer ,  David J. Livingston ,  Saroop Singh Matharu ,  Michael D. Mullican ,  Mark A. Murcko ,  Robert Murdoch ,  Robert E. Zelle

发明人： Mark James Batchelor ,  David Bebbington ,  Guy W. Bemis ,  Wolf Herman Fridman ,  Roger John Gillespie ,  Julian M. C. Golec ,  David J. Lauffer ,  David J. Livingston ,  Saroop Singh Matharu ,  Michael D. Mullican ,  Mark A. Murcko ,  Robert Murdoch ,  Robert E. Zelle

IPC分类号： A61K38/00 ,  C07K5/02 ,  C07D217/22 ,  A61K31/47 ,  C07D217/16

CPC分类号： C07K5/0202 ,  A61K38/00

摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1.beta. converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against an IL-1 mediated disease, an apoptosis mediated disease, AML, CML, melanoma, myeloma, Kaposi's sarcoma, graft vs host disease, rheumatoid arthritis, inflammatory bowel disorder, psoriasis, osteoarthritis, myeloma, apoptosis, sepsis, rheumatoid arthritis, asthma, Alzheimer's disease, Parkinson's disease, and ischemic heart disease diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

摘要翻译： 本发明涉及作为白细胞介素-1β转换酶抑制剂的新型化合物。 本发明的ICE抑制剂的特征在于具体的结构和物理化学特征。 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合于抑制ICE活性，因此可有利地用作抗IL-1介导的疾病，细胞凋亡介导的疾病，AML，CML，黑素瘤，骨髓瘤，卡波西氏肉瘤，移植物 与宿主疾病，类风湿性关节炎，炎性肠病，牛皮癣，骨关节炎，骨髓瘤，凋亡，败血症，类风湿性关节炎，哮喘，阿尔茨海默病，帕金森病和缺血性心脏病疾病相关。 本发明还涉及使用本发明的化合物和组合物来抑制ICE活性的方法和用于治疗白细胞介素-1介导的疾病的方法。