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1. 发明授权

US06531474B1 Inhibitors of caspases 有权
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.

2. 发明授权

US08691848B2 Inhibitors of caspases 有权
标题翻译：胱天蛋白酶抑制剂
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。

3. 发明申请

US20090048226A1 Inhibitors of caspases 有权
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.

4. 发明授权

US06573259B2 Inhibitors of interleukin-1&bgr; converting enzyme 失效
标题翻译：白细胞介素-1β转换酶抑制剂
公开(公告)号：US06573259B2
公开(公告)日：2003-06-03
申请号：US10035850
申请日：2001-10-23
申请人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Mark A. Murcko , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
发明人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Mark A. Murcko , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
IPC分类号： A61K3155
CPC分类号： C07K5/0821 , A61K38/00 , C07K5/0202 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/475
摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&bgr; converting enzyme (“ICE”). 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-(“IL-1”), apoptosis-, interferon-&ggr; inducing factor-(IGIF), interferon-&ggr;-(“IFN-&ggr;”) mediated diseases, excess dietary alcohol intake diseases, or viral diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting ICE 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.
摘要翻译：本发明涉及作为白细胞介素-1β转换酶（“ICE”）抑制剂的新型化合物。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细胞介素-1-（“IL-1”），细胞凋亡，干扰素-γ诱导因子（IGIF）干扰素-γ-（“IFN-γ”）介导的疾病，过度饮食酒精摄入疾病或病毒性疾病，包括炎性疾病，自身免疫疾病，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ICE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，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。

5. 发明授权

US06974809B2 Inhibitors of interleukin 1-β converting enzyme 失效
标题翻译：白介素1-β转换酶抑制剂
公开(公告)号：US06974809B2
公开(公告)日：2005-12-13
申请号：US10424576
申请日：2003-04-25
申请人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Mark A. Murcko , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
发明人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Mark A. Murcko , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
IPC分类号： A61K38/00 , A61K38/55 , A61P1/00 , A61P1/18 , A61P7/00 , A61P9/10 , A61P17/06 , A61P19/02 , A61P25/00 , A61P25/16 , A61P25/28 , A61P29/00 , A61P31/04 , A61P31/12 , A61P31/14 , A61P35/00 , A61P35/02 , A61P37/06 , A61P43/00 , C07K5/02 , C07K5/023 , C07K5/097 , C07D491/00 , C07D495/00 , A61K31/55
CPC分类号： C07K5/0821 , A61K38/00 , C07K5/0202 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/475
摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme (“ICE”). 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-(“IL-1”), apoptosis-, interferon-γ inducing factor-(IGIF), interferon-γ-(“IFN-γ”) mediated diseases, excess dietary alcohol intake diseases, or viral diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting ICE 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：本发明涉及作为白细胞介素-1β转换酶（“ICE”）抑制剂的新型化合物。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细胞介素-1-（“IL-1”），细胞凋亡，干扰素-γ诱导因子（IGIF）干扰素-γ-（“IFN-γ”）介导的疾病，过度饮食酒精摄入疾病或病毒性疾病，包括炎性疾病，自身免疫疾病，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ICE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，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。

6. 发明授权

US06329365B1 Inhibitors of interleukin-1&bgr; converting enzyme 失效
标题翻译：白细胞介素-1β转换酶抑制剂
公开(公告)号：US06329365B1
公开(公告)日：2001-12-11
申请号：US09326495
申请日：1999-06-04
申请人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Mark A. Murcko , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
发明人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Mark A. Murcko , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
IPC分类号： A61K3155
CPC分类号： C07K5/0821 , A61K38/00 , C07K5/0202 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/475
摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&bgr; converting enzyme (“ICE”). 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-(“IL-1”), apoptosis-, interferon-&ggr; inducing factor-(IGIF), interferon-&ggr;-(“IFN-&ggr;”) mediated diseases, excess dietary alcohol intake diseases, or viral diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting ICE 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.
摘要翻译：本发明涉及作为白细胞介素-1β转换酶（“ICE”）抑制剂的新型化合物。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细胞介素-1-（“IL-1”），细胞凋亡，干扰素-γ诱导因子（IGIF）干扰素-γ-（“IFN-γ”）介导的疾病，过度饮食酒精摄入疾病或病毒性疾病，包括炎性疾病，自身免疫疾病，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ICE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，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。

7. 发明授权

US06350741B1 Inhibitors of interleukin-1&bgr; converting enzyme 失效
标题翻译：白细胞介素-1β转换酶抑制剂
公开(公告)号：US06350741B1
公开(公告)日：2002-02-26
申请号：US09326494
申请日：1999-06-04
申请人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
发明人： Julian M. C. Golec , David J. Lauffer , David J. Livingston , Michael D. Mullican , Philip L. Nyce , Andrea L. C. Robidoux , Marion W. Wannamaker
IPC分类号： A61K3155
CPC分类号： C07K5/06139 , A61K38/00 , C07K5/0202 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/475
摘要： The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&bgr; converting enzyme (“ICE”). 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-(“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 ICE 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.
摘要翻译：本发明涉及作为白细胞介素-1β转换酶（“ICE”）抑制剂的新型化合物。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细胞介素-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ICE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，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。

8. 发明授权

US06426413B1 Inhibitors of caspases 失效
标题翻译：胱天蛋白酶抑制剂
公开(公告)号：US06426413B1
公开(公告)日：2002-07-30
申请号：US09654855
申请日：2000-09-05
申请人： Marion W. Wannamaker , Paul Charifson , David J. Lauffer , Michael D. Mullican
发明人： Marion W. Wannamaker , Paul Charifson , David J. Lauffer , Michael D. Mullican
IPC分类号： C07D24302
CPC分类号： C07D401/12 , C07D243/02 , C07D401/14 , C07D405/12
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.
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-1β转换酶（“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细胞介素-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胱天蛋白酶活性和降低IGIF产生和IFN-γ产生的方法以及用于治疗白介素-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。

9. 发明授权

US07691853B2 Pyrazole compounds useful as protein kinase inhibitors 失效
标题翻译：用作蛋白激酶抑制剂的吡唑化合物
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。

10. 发明授权

US07872129B2 Compositions useful as inhibitors of GSK-3 有权
标题翻译：可用作GSK-3抑制剂的组合物
公开(公告)号：US07872129B2
公开(公告)日：2011-01-18
申请号：US12338129
申请日：2008-12-18
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以及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。

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