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    Bis(thio-hydrazide amide) salts for treatment of cancers
    2.
    发明授权
    Bis(thio-hydrazide amide) salts for treatment of cancers 有权
    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。

    BIS(THIO-HYDRAZIDE AMIDE) SALTS FOR TREATMENT OF CANCERS
    3.
    发明申请
    BIS(THIO-HYDRAZIDE AMIDE) SALTS FOR TREATMENT OF CANCERS 有权
    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。

    Synthesis of taxol enhancers
    4.
    发明申请
    Synthesis of taxol enhancers 失效
    紫杉醇增强剂的合成

    公开(公告)号：US20090005594A1

    公开(公告)日：2009-01-01

    申请号：US12231217

    申请日：2008-08-29

    申请人： Shoujun Chen ,  Lijun Sun ,  Zhi-Qiang Xia ,  Keizo Kova ,  Mitsunori Ono

    发明人： Shoujun Chen ,  Lijun Sun ,  Zhi-Qiang Xia ,  Keizo Kova ,  Mitsunori Ono

    IPC分类号： C07C327/00

    CPC分类号： C07D213/77 ,  C07C327/56 ,  C07C2601/14 ,  C07D209/42 ,  C07D209/44 ,  C07D213/83 ,  C07D261/18 ,  C07D307/54 ,  C07D333/38 ,  Y02P20/55

    摘要： Disclosed is a method of preparing a thiohydrazide product compound from a hydrazide starting compound. The hydrazide starting compound is represented by Structural Formula (I): The thiohydrazide product compound is represented by Structural Formula (II): In Structural Formulas (I)-(II), R1 and R2 are independently an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R2 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. When R2 is an aryl group or a substituted aryl group, then R5 is a hydrazine protecting group; and when R2 is an aliphatic or substituted aliphatic group, then R5 is —H or a hydrazine protecting group. R10 is —H or a substituted or unsubstituted alkyl group. The method comprising the step of reacting the starting compound with a thionylating reagent.

    摘要翻译： 公开了从酰肼起始化合物制备硫代酰肼产物化合物的方法。 酰肼起始化合物由结构式（I）表示：硫代酰肼产物化合物由结构式（II）表示：在结构式（I） - （II）中，R 1和R 2独立地为脂族基团，取代的脂族基团 ，芳基或取代的芳基，或者R 1和R 2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。 当R 2为芳基或取代芳基时，R 5为肼保护基; 当R 2为脂肪族或取代的脂族基团时，R 5为-H或肼保护基。 R 10为-H或取代或未取代的烷基。 该方法包括使起始化合物与亚硫酰化试剂反应的步骤。

    Paclitaxel enhancer compound
    9.
    发明授权
    Paclitaxel enhancer compound 失效
    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。