公开(公告)号：US06660758B1

公开(公告)日：2003-12-09

申请号：US09319885

申请日：1999-09-24

申请人： Kyriacos C. Nicolaou ,  Yun He ,  Sacha Ninkovic ,  Joaquin Pastor ,  Frank Roschangar ,  Francisco Sarabia ,  Hans Vallberg ,  Dionisios Vourloumis ,  Nicolas Winssinger ,  Zhen Yang ,  Nigel Paul King ,  M. Ray Finlay

发明人： Kyriacos C. Nicolaou ,  Yun He ,  Sacha Ninkovic ,  Joaquin Pastor ,  Frank Roschangar ,  Francisco Sarabia ,  Hans Vallberg ,  Dionisios Vourloumis ,  Nicolas Winssinger ,  Zhen Yang ,  Nigel Paul King ,  M. Ray Finlay

IPC分类号： C07D41306

CPC分类号： C07D417/06 ,  C07D313/00 ,  C07D493/04

摘要： Epothilone A, epothilone B, analogs of epothilone and libraries of epothilone analogs are synthesized. Epothilone A and B are known anticancers agents that derive their anticancer activity by the prevention of mitosis through the induction and stabilization of microtubule assembly. The analogs of epothilone are novel. Several of the analogs are demonstrated to have a superior cytotoxic activity as compared to epothilone A or epothilone B as demonstrated by their enhanced ability to induce the polymerization and stabilization of microtubules.

摘要翻译： 埃博霉素A，埃坡霉素B，埃坡霉素类似物和埃坡霉素类似物文库合成。 埃博霉素A和B是已知的抗癌剂，通过微管组装的诱导和稳定来预防有丝分裂，从而获得抗癌活性。 埃坡霉素的类似物是新颖的。 与埃坡霉素A或埃坡霉素B相比，几种类似物被证明具有优异的细胞毒性活性，如通过增强诱导微管聚合和稳定化的能力所证实的。

公开(公告)号：US06441186B1

公开(公告)日：2002-08-27

申请号：US08923869

申请日：1997-09-04

申请人： Kyriacos C. Nicolaou ,  Yun He ,  Sacha Ninkovic ,  Joaquin Pastor ,  Frank Roschangar ,  Francisco Sarabia ,  Hans Vallberg ,  Dionisios Vourloumis ,  Nicolas Winssinger ,  Zhen Yang ,  N. Paul King ,  M. Ray Finlay

发明人： Kyriacos C. Nicolaou ,  Yun He ,  Sacha Ninkovic ,  Joaquin Pastor ,  Frank Roschangar ,  Francisco Sarabia ,  Hans Vallberg ,  Dionisios Vourloumis ,  Nicolas Winssinger ,  Zhen Yang ,  N. Paul King ,  M. Ray Finlay

IPC分类号： C07D41714

CPC分类号： C07D417/06 ,  C07D313/00 ,  C07D493/04

摘要： Epothilone A, epothilone B, analogs of epothilone and libraries of epothilone analogs are synthesized. Epothilone A and B are known anticancer agents that derive their anticancer activity by the prevention of mitosis through the induction and stabilization of microtubulin assembly. The analogs of epothilone are novel. Several of the anlogs are demonstrated to have a superior cytotoxic activities as compared to epothilone A or epothilone B as demonstrated by their enhanced ability to induce the polymerization and stabilization of microtubules.

摘要翻译： 埃博霉素A，埃坡霉素B，埃坡霉素类似物和埃坡霉素类似物文库合成。 埃博霉素A和B是已知的抗癌剂，其通过微管蛋白装配的诱导和稳定来预防有丝分裂来获得它们的抗癌活性。 埃坡霉素的类似物是新颖的。 与埃坡霉素A或埃坡霉素B相比，其中的几个log被证明具有优异的细胞毒性活性，如通过增强诱导微管聚合和稳定化的能力所证实的。

公开(公告)号：US06380394B1

公开(公告)日：2002-04-30

申请号：US09102602

申请日：1998-06-22

申请人： Kyriacos C. Nicolaou ,  N. Paul King ,  M. Ray Finlay ,  Yun He ,  Frank Roschangar ,  Dionisios Vourloumis ,  Hans Vallberg ,  Francisco Sarabia ,  Sacha Ninkovic ,  David Hepworth ,  Tianhu Li

发明人： Kyriacos C. Nicolaou ,  N. Paul King ,  M. Ray Finlay ,  Yun He ,  Frank Roschangar ,  Dionisios Vourloumis ,  Hans Vallberg ,  Francisco Sarabia ,  Sacha Ninkovic ,  David Hepworth ,  Tianhu Li

IPC分类号： C07D27100

CPC分类号： C07D313/00 ,  C07D417/06 ,  C07D493/04 ,  Y02P20/55

摘要： Novel analogs of epothilone A, epothilone B, and epothilone C are synthesized by Stille coupling thazole-stannanes to macrolactone intermediates. The synthetic epothilone analogs selectively prevent mitosis in cancer cells through the induction and stabilization of microtubulin assembly. Selected synthetic epothilone analogs are demonstrated to have greater bioactivity than their corresponding native compound.

摘要翻译： 埃博霉素A，埃坡霉素B和埃坡霉素C的新型类似物由Stille偶联唑 - 锡烷合成为大环内酯中间体。 合成的埃坡霉素类似物通过微管蛋白装配的诱导和稳定选择性地防止癌细胞中的有丝分裂。 所选的合成埃坡霉素类似物被证明具有比其相应的天然化合物更大的生物活性。