公开(公告)号：US20110251188A1

公开(公告)日：2011-10-13

申请号：US13128381

申请日：2009-10-25

申请人： Zhichao Zhang ,  Guiye Wu ,  Ting Song ,  Feibo Xie

发明人： Zhichao Zhang ,  Guiye Wu ,  Ting Song ,  Feibo Xie

IPC分类号： A61K31/541 ,  A61P35/00 ,  A61K31/403 ,  C08B37/16 ,  C07D209/94 ,  C07D417/10

CPC分类号： C07D209/70 ,  A61K31/403 ,  A61K31/54 ,  C07D405/12 ,  C07D409/12 ,  C08B37/0015

摘要： The present invention relates to acenaphtho heterocyclic compounds, cyclodextrin inclusion compounds and complexes thereof, and their uses in manufacturing the inhibitors of BH3 analogue, Bcl-2 family proteins. The acenaphtho heterocyclic compounds are obtained by introducing oxo-, thio-, carbonyl, ester or acyl in the 3-, 4- and 6-position of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile, or further substituting 9-cyano with carboxyl, ester or amide. The compounds can simulate BH3-only protein, competitively binding and antagonizing Bcl-2, Bel-XL and Mcl-1 proteins in vitro or intracellular, to induce cell apoptosis. The cyclodextrin inclusion compounds and complexes can improve the effects. Therefore, they all can be used in the manufactures of anticancer compounds.

摘要翻译： 本发明涉及苊萘杂环化合物，环糊精包合物及其复合物，以及它们在制备BH3类似物Bcl-2家族蛋白抑制剂中的应用。 通过在8-氧代-8H-苊并[1,2-b]吡咯-9-腈的3-，4-和6-位引入氧代，硫代，羰基，酯或酰基，得到苊并杂环化合物 或进一步用羧基，酯或酰胺代替9-氰基。 该化合物可以模拟BH3蛋白，体外或细胞内竞争性结合和拮抗Bcl-2，Bel-XL和Mcl-1蛋白，诱导细胞凋亡。 环糊精包合物和配合物可以改善效果。 因此，它们都可用于抗癌化合物的制造。

公开(公告)号：US08614333B2

公开(公告)日：2013-12-24

申请号：US13810901

申请日：2011-07-27

申请人： Zhichao Zhang ,  Guiye Wu

发明人： Zhichao Zhang ,  Guiye Wu

IPC分类号： C07D209/80 ,  C07D417/10

CPC分类号： C07D209/80 ,  C07D209/70 ,  C07D417/10

摘要： The present invention relates to acenaphtho heterocyclic compounds and their uses in manufacturing the BH3 mimetics as Bcl-2-like protein inhibitors. Structures are shown in the following: Statistical analysis of their bio-activities showed these compounds exhibit better BH3 mimicking property than the reported compounds. These compounds can simulate BH3-only protein, competitively bind and antagonizing Bcl-2 and Mcl-1 proteins in vitro and in cells, and then induce apoptosis. Therefore, they all can be used in the manufactures of anticancer compounds.

摘要翻译： 本发明涉及苊萘杂环化合物及其在制造BH3模拟物中作为Bcl-2样蛋白抑制剂的用途。 结构如下所示：其生物活性的统计分析表明，这些化合物比所报道的化合物表现出更好的BH3模拟性质。 这些化合物可以模拟BH3蛋白，在体外和细胞中竞争性地结合和拮抗Bcl-2和Mcl-1蛋白，然后诱导细胞凋亡。 因此，它们都可用于抗癌化合物的制造。

公开(公告)号：US20130123492A1

公开(公告)日：2013-05-16

申请号：US13810901

申请日：2011-07-27

申请人： Zhichao Zhang ,  Guiye Wu

发明人： Zhichao Zhang ,  Guiye Wu

IPC分类号： C07D209/80 ,  C07D417/10

CPC分类号： C07D209/80 ,  C07D209/70 ,  C07D417/10

摘要： The present invention relates to acenaphtho heterocyclic compounds and their uses in manufacturing the BH3 mimetics as Bcl-2-like protein inhibitors. Structures are shown in the following: Statistical analysis of their bio-activities showed these compounds exhibit better BH3 mimicking property than the reported compounds. These compounds can simulate BH3-only protein, competitively bind and antagonizing Bcl-2 and Mcl-1 proteins in vitro and in cells, and then induce apoptosis. Therefore, they all can be used in the manufactures of anticancer compounds.

摘要翻译： 本发明涉及苊萘杂环化合物及其在制造BH3模拟物中作为Bcl-2样蛋白抑制剂的用途。 结构如下所示：其生物活性的统计分析表明，这些化合物比所报道的化合物表现出更好的BH3模拟性质。 这些化合物可以模拟BH3蛋白，在体外和细胞中竞争性地结合和拮抗Bcl-2和Mcl-1蛋白，然后诱导细胞凋亡。 因此，它们都可用于抗癌化合物的制造。