公开(公告)号：US5965718A

公开(公告)日：1999-10-12

申请号：US145376

申请日：1998-09-01

申请人： Kyriacos C. Nicolaou ,  Floris VanDelft ,  Seijiro Hosokawa ,  Sanghee Kim ,  Tianhu Li ,  Takashi Ohshima ,  Jeff Pfefferkorn ,  Dionisios Vourloumis ,  Jin-You Xu ,  Nicolas Winssinger

发明人： Kyriacos C. Nicolaou ,  Floris VanDelft ,  Seijiro Hosokawa ,  Sanghee Kim ,  Tianhu Li ,  Takashi Ohshima ,  Jeff Pfefferkorn ,  Dionisios Vourloumis ,  Jin-You Xu ,  Nicolas Winssinger

IPC分类号： C07H15/26 ,  A61K31/34 ,  A61K31/4164 ,  A61K31/422 ,  A61K31/427 ,  A61K31/443 ,  A61K31/7028 ,  A61K31/7048 ,  A61P35/00 ,  A61P43/00 ,  C07D493/08 ,  C07F7/18 ,  C07H15/24 ,  A61K31/70 ,  C07D307/77

CPC分类号： C07D493/08

摘要： Sarcodictyin A and B, eleutherobin, and bioactive analogs thereof synthesized using solid phase and solution phase chemistries. The synthetic method employs an attachment of common precursors, e.g., compounds 1880 or 200, on a solid support for generating conjugates 230 and 240, followed by standard chemical manipulations. A combinatorial library of sarcodictyins and eletherobin analogs was constructed with modified C-8 ester, C-15 ester and C-4 ketal functionalities and was screened for activity with respect to tubulin polymerization and cytotoxic activity against tumor cells, including Taxol-resistant lines. Compounds 600, 610, 630, 660-700, 730, 760, 850, and 920 were identified to be of equal or superior biological activities as compared to their corresponding natural product.

摘要翻译： Sarcodictyin A和B，eleutherobin及其使用固相和溶液相化学合成的生物活性类似物。 合成方法使用常用前体（例如化合物1880或200）在固体支持物上的附着，用于产生共轭物230和240，随后进行标准化学操作。 用修饰的C-8酯，C-15酯和C-4缩酮官能团构建了链霉菌素和eletherobin类似物的组合文库，并筛选了关于微管蛋白聚合和抗肿瘤细胞（包括耐紫杉醇系）的细胞毒活性的活性。 与其相应的天然产物相比，化合物600,610,630,660-700,730,760,850和920被鉴定为具有相同或优异的生物活性。