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1. 发明授权

US08461208B2 Bis(thio-hydrazide amide) salts for treatment of cancers 有权
标题翻译：用于治疗癌症的双（硫代酰肼）酰胺盐
公开(公告)号：US08461208B2
公开(公告)日：2013-06-11
申请号：US13273807
申请日：2011-10-14
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/16
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts and pharmaceutical compositions thereof. Also disclosed are methods of using bis(thio-hydrazide amide) disalts to treat cancer.
摘要翻译：公开了双（硫代酰肼酰胺）二盐及其药物组合物。还公开了使用双（硫代酰肼酰胺）狄尔斯治疗癌症的方法。

2. 发明申请

US20060135595A1 Bis(thio-hydrazide amide) salts for treatment of cancers 有权
标题翻译：用于治疗癌症的双（硫代酰肼）酰胺盐
公开(公告)号：US20060135595A1
公开(公告)日：2006-06-22
申请号：US11157213
申请日：2005-06-20
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/4015 , A61K31/16
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地是-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或R 1， SUB和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4结合在一起与其键合的碳原子和氮原子形成任选地稠合到芳香环的非芳族杂环。 Z是-O或-S。 M + +是药学上可接受的一价阳离子，M 2 +是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

3. 发明授权

US08048925B2 Bis(thio-hydrazide amide) salts for treatment of cancers 有权
标题翻译：用于治疗癌症的双（硫代酰肼）酰胺盐
公开(公告)号：US08048925B2
公开(公告)日：2011-11-01
申请号：US12871587
申请日：2010-08-30
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/16
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation.Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

4. 发明申请

US20090281172A1 BIS(THIO-HYDRAZIDE AMIDE) SALTS FOR TREATMENT OF CANCERS 有权
标题翻译： BIS（THIO-HYDRAZIDE AMIDE）用于治疗癌症的药物
公开(公告)号：US20090281172A1
公开(公告)日：2009-11-12
申请号：US12503661
申请日：2009-07-15
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/166 , A61P35/00 , C07C327/48 , A61K31/337
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation.Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

5. 发明授权

US07795313B2 Bis(thio-hydrazide amide) salts for treatment of cancers 有权
标题翻译：用于治疗癌症的双（硫代酰肼）酰胺盐
公开(公告)号：US07795313B2
公开(公告)日：2010-09-14
申请号：US12503661
申请日：2009-07-15
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/16
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

6. 发明授权

US07579503B2 BIS (thio-hydrazide amide) salts for treatment of cancers 失效
标题翻译：用于治疗癌症的BIS（硫代酰肼）酰胺盐
公开(公告)号：US07579503B2
公开(公告)日：2009-08-25
申请号：US12148312
申请日：2008-04-18
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： C07C327/38 , A61K31/16
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation.Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

7. 发明申请

US20120035266A1 BIS(THIO-HYDRAZIDE AMIDE) SALTS FOR TREATMENT OF CANCERS 有权
标题翻译： BIS（THIO-HYDRAZIDE AMIDE）用于治疗癌症的药物
公开(公告)号：US20120035266A1
公开(公告)日：2012-02-09
申请号：US13273807
申请日：2011-10-14
申请人： Keizo KOYA , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo KOYA , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/16 , A61P35/00
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts and pharmaceutical compositions thereof. Also disclosed are methods of using bis(thio-hydrazide amide) disalts to treat cancer.
摘要翻译：公开了双（硫代酰肼酰胺）二盐及其药物组合物。还公开了使用双（硫代酰肼酰胺）狄尔斯治疗癌症的方法。

8. 发明申请

US20100324143A1 BIS(THIO-HYDRAZIDE AMIDE) SALTS FOR TREATMENT OF CANCERS 有权
标题翻译： BIS（THIO-HYDRAZIDE AMIDE）用于治疗癌症的药物
公开(公告)号：US20100324143A1
公开(公告)日：2010-12-23
申请号：US12871587
申请日：2010-08-30
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/166 , A61P35/00 , A61P35/02
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

9. 发明授权

US07385084B2 Bis(thio-hydrazide amide) salts for treatment of cancers 有权
标题翻译：用于治疗癌症的双（硫代酰肼）酰胺盐
公开(公告)号：US07385084B2
公开(公告)日：2008-06-10
申请号：US11157213
申请日：2005-06-20
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Tatsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： C07C327/38 , A61K31/16
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation.Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地是-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或R 1， SUB和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4结合在一起与其键合的碳原子和氮原子形成任选地稠合到芳香环的非芳族杂环。 Z是-O或-S。 M + +是药学上可接受的一价阳离子，M 2 +是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

10. 发明申请

US20080269340A1 BIS (thio-hydrazide amide) salts for treatment of cancers 失效
标题翻译：用于治疗癌症的BIS（硫代酰肼）酰胺盐
公开(公告)号：US20080269340A1
公开(公告)日：2008-10-30
申请号：US12148312
申请日：2008-04-18
申请人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Taitsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Elena Kostik , Farid Vaghefi , Shoujun Chen , Noriaki Taitsuta , Guiqing Liang , Takayo Inoue , Zhi-Qiang Xia
IPC分类号： A61K31/166 , C07C327/38
CPC分类号： C07D305/14 , C07C327/56 , C07C2601/02
摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation.Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.
摘要翻译：公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地是-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或R 1， SUB和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4结合在一起与其键合的碳原子和氮原子形成任选地稠合到芳香环的非芳族杂环。 Z是-O或-S。 M + +是药学上可接受的一价阳离子，M 2+是药学上可接受的二价阳离子。还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。进一步公开的是用癌症治疗受试者的方法。所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

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