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1. 发明授权

US5599825A Water-soluble methine compound and pharmaceutical composition for treatment of cancer comprising the same 失效
标题翻译：水溶性次甲基化合物和用于治疗癌症的药物组合物
公开(公告)号：US5599825A
公开(公告)日：1997-02-04
申请号：US420481
申请日：1995-04-12
申请人： Noriaki Tatsuta , Akihiko Okegawa , Masayuki Kawakami , Keizo Koya
发明人： Noriaki Tatsuta , Akihiko Okegawa , Masayuki Kawakami , Keizo Koya
IPC分类号： C07D277/64 , C07D277/84 , C07D417/14 , A61K31/425 , C07D417/06
CPC分类号： C07D417/14 , C07D277/64 , C07D277/84
摘要： There are provided methine compounds having the following structure and their analogs, with a high solubility and are usefull as an active ingredient for pharmaceutical composition for treatment of cancer: ##STR1##
摘要翻译：提供具有以下结构的次甲基化合物及其类似物，具有高溶解性，并且作为用于治疗癌症的药物组合物的活性成分是有用的： + TR + TR

2. 发明申请

US20100311840A1 ORAL FORMULATIONS OF BIS(THIOHYDRAZIDE AMIDES) 失效
标题翻译： BIS（THIOHYDRAZIDE AMIDES）的口服制剂
公开(公告)号：US20100311840A1
公开(公告)日：2010-12-09
申请号：US12741486
申请日：2008-11-07
申请人： Noriaki Tatsuta , Takayo Inoue , Keizo Koya
发明人： Noriaki Tatsuta , Takayo Inoue , Keizo Koya
IPC分类号： A61K31/165 , A61P25/28 , A61P25/16 , A61P25/14 , A61P21/00 , A61P9/10 , A61P27/06 , A61P31/04 , A61P31/12 , A61P33/00 , A61P31/10
CPC分类号： A61K9/19 , A61K9/1075 , A61K31/16 , A61K31/165
摘要： Disclosed herein are oral formulations of bis(thio-hydrazide amides) compounds of the following structural formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R7, R8, Z, and Y are defined herein.
摘要翻译：本文公开了以下结构式（I）的双（硫代酰肼酰胺）化合物或其药学上可接受的盐的口服制剂，其中R 1，R 2，R 3，R 4，R 7，R 8，Z和Y在本文中定义。

3. 发明授权

US07750042B2 Paclitaxel enhancer compound 失效
标题翻译：紫杉醇增强剂化合物
公开(公告)号：US07750042B2
公开(公告)日：2010-07-06
申请号：US12077729
申请日：2008-03-20
申请人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono , Zhi-Qiang Xia
IPC分类号： A61K31/335 , A61K31/20 , C07C327/38 , C07C243/18
CPC分类号： C07D307/68 , A45D2008/006 , A61K31/337 , A61K31/505 , A61K31/53 , A61K31/5377 , A61K47/58 , C07C327/56 , C07C2601/02 , C07C2601/04 , C07C2601/08 , C07C2601/14 , C07D209/42 , C07D209/44 , C07D213/83 , C07D261/18 , C07D333/38 , C07D333/68
摘要： One embodiment of the present invention is a compound represented by the Structural Formula (I): Y is a covalent bond of a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C═Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R7R8)—. R1 is an aliphatic group, a substituted aliphatic group, a non-aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group, R2-R4 are independently —H, an aliphatic group, a substituted aliphatic group, a non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic 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. R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R7 and R8 are each independently —H, an aliphatic or substituted aliphatic group, or R7 is —H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent.
摘要翻译：本发明的一个实施方案是由结构式（I）表示的化合物：Y是取代或未取代的直链烃基的共价键。此外，Y与它所键合的两个> C = Z基团一起是取代或未取代的芳族基团。优选Y为共价键或-C（R 7 R 8） - 。 R1是脂肪族基团，取代脂肪族基团，非芳族杂环基团或取代的非芳族杂环基团，R2-R4独立地是-H，脂肪族基团，取代的脂肪族基团，非芳香族杂环基，取代的非芳族杂环基，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与碳和氮原子一起形成与芳环稠合的非芳族杂环。 R5-R6独立地是-H，脂族基团，取代的脂族基团，芳基或取代的芳基。 R 7和R 8各自独立地为-H，脂族或取代的脂族基团，或者R 7为-H且R 8为取代或未取代的芳基，或者R 7和R 8一起为C 2 -C 6取代或未取代的亚烷基。 Z为═O或═S。还公开了包含本发明化合物和药学上可接受的载体或稀释剂的药物组合物。

4. 发明授权

US07345094B2 Paclitaxel enhancer compounds 有权
公开(公告)号：US07345094B2
公开(公告)日：2008-03-18
申请号：US11244324
申请日：2005-10-05
申请人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono
发明人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono
IPC分类号： A61K31/16 , C07C327/00 , C07C233/00
CPC分类号： A61K47/48176 , A61K31/16 , A61K31/165 , A61K31/277 , A61K31/337 , A61K31/381 , A61K31/44 , A61K31/505 , A61K31/53 , A61K47/58 , C07C327/56 , C07C2601/02 , C07C2601/04 , C07C2601/08 , C07C2601/14 , C07D209/42 , C07D209/44 , C07D213/83 , C07D261/18 , C07D305/14 , C07D307/68 , C07D333/38 , C07D333/68 , C07D407/12
摘要： Disclosed is a compound represented by the Structural Formula (I): Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R7R8)—. R1 and R2 are independently an aryl group or a substituted aryl group, R3 and R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R7 and R8 are each independently —H, an aliphatic or substituted aliphatic group, or R7 is —H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with Paclitaxel or an analog of Paclitaxel.

5. 发明申请

US20060116374A1 Taxol enhancer compounds 有权
标题翻译：紫杉醇增强剂化合物
公开(公告)号：US20060116374A1
公开(公告)日：2006-06-01
申请号：US11244427
申请日：2005-10-05
申请人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono , Zhi-Qiang Xia
发明人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono , Zhi-Qiang Xia
IPC分类号： A61K31/5377 , A61K31/53 , A61K31/505 , A61K31/337
CPC分类号： C07D307/68 , A45D2008/006 , A61K31/337 , A61K31/505 , A61K31/53 , A61K31/5377 , A61K47/58 , C07C327/56 , C07C2601/02 , C07C2601/04 , C07C2601/08 , C07C2601/14 , C07D209/42 , C07D209/44 , C07D213/83 , C07D261/18 , C07D333/38 , C07D333/68
摘要： One embodiment of the present invention is a compound represented by the Structural Formula (I): Y is a covalent bond of a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R7R8)—. R1 is an aliphatic group, a substituted aliphatic group, a non-aromatic heterocyclic group, or a substituted non-aromatic heterocyclic group, R2-R4 are independently —H, an aliphatic group, a substituted aliphatic group, a non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic 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. R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R7 and R8 are each independently —H, an aliphatic or substituted aliphatic group, or R7 is —H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent.
摘要翻译：本发明的一个实施方案是由结构式（I）表示的化合物：Y是取代或未取代的直链烃基的共价键。此外，Y与它所键合的两个> C = Z基团一起是取代或未取代的芳族基团。优选地，Y是共价键或-C（R 7 R 8） - 。 R 1是脂族基团，取代的脂族基团，非芳族杂环基团或取代的非芳香族杂环基团，R 2 -R 4 独立地，-H，脂族基团，取代的脂族基团，非芳香族杂环基，取代的非芳族杂环基，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。 R 5 -R 6独立地是-H，脂族基团，取代的脂族基团，芳基或取代的芳基。 R 7和R 8各自独立地为-H，脂族或取代的脂族基团或R 7为-H， 8是取代或未取代的芳基，或者R 7和R 8一起是C2-C6取代或未取代的亚烷基。 Z是-O或-S。还公开了包含本发明化合物和药学上可接受的载体或稀释剂的药物组合物。

6. 发明授权

US08618170B2 Oral formulations of bis(thiohydrazide amides) 失效
标题翻译：双（硫代酰肼）酰胺的口服制剂
公开(公告)号：US08618170B2
公开(公告)日：2013-12-31
申请号：US12741486
申请日：2008-11-07
申请人： Noriaki Tatsuta , Takayo Inoue , Keizo Koya
发明人： Noriaki Tatsuta , Takayo Inoue , Keizo Koya
IPC分类号： A61K31/16
CPC分类号： A61K9/19 , A61K9/1075 , A61K31/16 , A61K31/165
摘要： Disclosed herein are oral formulations of bis(thio-hydrazide amides) compounds of the following structural formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R7, R8, Z, and Y are defined herein.
摘要翻译：本文公开了以下结构式（I）的双（硫代酰肼酰胺）化合物或其药学上可接受的盐的口服制剂，其中R 1，R 2，R 3，R 4，R 7，R 8，Z和Y在本文中定义。

7. 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。

8. 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。

9. 发明授权

US06924312B2 Taxol enhancer compounds 失效
标题翻译：紫杉醇增强剂化合物
公开(公告)号：US06924312B2
公开(公告)日：2005-08-02
申请号：US10345885
申请日：2003-01-15
申请人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono
发明人： Keizo Koya , Lijun Sun , Shoujun Chen , Noriaki Tatsuta , Yaming Wu , Mitsunori Ono
IPC分类号： A45D8/00 , A45D8/12 , A45D8/20 , A45D8/36 , A61K31/337 , C07C327/56 , C07D209/42 , C07D209/44 , C07D213/83 , C07D261/18 , C07D307/68 , C07D333/38 , C07D333/68 , A61K31/16 , C07C241/00
CPC分类号： C07D307/68 , A45D2008/006 , A61K31/337 , A61K47/58 , C07C327/56 , C07C2601/02 , C07C2601/04 , C07C2601/08 , C07C2601/14 , C07D209/42 , C07D209/44 , C07D213/83 , C07D261/18 , C07D333/38 , C07D333/68
摘要： Disclosed is a compound represented by the Structural Formula (I): Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C═Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R7R8)—. R1 and R2 are independently an aryl group or a substituted aryl group, R3 and R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R7 and R8 are each independently —H, an aliphatic or substituted aliphatic group, or R7 is —H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with taxol or an analog of taxol.
摘要翻译：公开了由结构式（I）表示的化合物：Y是共价键，亚苯基或取代或未取代的直链烃基。此外，Y与它所键合的两个> C-Z基团一起是取代或未取代的芳族基团。优选地，Y是共价键或-C（R 7 R 8） - 。 R 1和R 2分别独立地是芳基或取代的芳基，R 3和R 4是独立的-H，脂族基团，取代的脂族基团，芳基或取代的芳基。 R 5 -R 6独立地是-H，脂族基团，取代的脂族基团，芳基或取代的芳基。 R 7和R 8各自独立地为-H，脂族或取代的脂族基团或R 7为-H， 8是取代或未取代的芳基，或者R 7和R 8一起是C2-C6取代或未取代的亚烷基。 Z是-O或-S。还公开了包含本发明化合物和药学上可接受的载体或稀释剂的药物组合物。还公开了通过向受试者施用结构式（I）的化合物与紫杉醇或紫杉醇的类似物组合治疗患有癌症的受试者的方法。

10. 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。

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