公开(公告)号：US5493012A

公开(公告)日：1996-02-20

申请号：US71116

申请日：1993-06-02

申请人： Steven E. Rokita ,  Tianhu Li ,  Qingping Zeng

发明人： Steven E. Rokita ,  Tianhu Li ,  Qingping Zeng

IPC分类号： C07D207/404 ,  C07F7/18 ,  C07H19/04 ,  C07H21/00 ,  C07H23/00 ,  C07H21/04

CPC分类号： C07D207/404 ,  C07F7/1852 ,  C07F7/1856 ,  C07H21/00 ,  C07H23/00

摘要： A silyloxy aromatic derivative capable of alkylating a target biological molecule when activated by ionic strength. A sequence directed reagent may be constructed by conjugating a methyl silyloxy aromatic derivative to a hexamethyiamino linker attached to either the 5' or 3' terminus of an oligonucleotide. Annealing this modified fragment of DNA to its complementary sequence allows for target modification subsequent to ionic activation. The product of this reaction is a covalent crosslink between the reagent and target strands resulting from an alkylation of DNA by the activated silyloxy aromatic derivative. In a preferred embodiment, a nitrophenyl or bromo group is attached to a methyl group of the silyloxy aromatic derivative. This reagent may be similarly linked to an oligonucleotide probe. Activation of the alkylating agent by an ionic signal (X) which may naturally occur, or may be introduced into the media containing the target molecule, such as by the introduction of a salt (MX).

摘要翻译： 当通过离子强度活化时，能够将靶生物分子烷基化的甲硅烷氧基芳族衍生物。 序列导向试剂可以通过将甲基甲硅烷氧基芳族衍生物与连接于寡核苷酸的5'或3'末端的六甲基氨基接头缀合来构建。 将该修饰的DNA片段退火至其互补序列允许在离子活化后进行靶修饰。 该反应的产物是由活化的甲硅烷氧基芳族衍生物的DNA烷基化产生的试剂和靶链之间的共价交联。 在优选的实施方案中，硝基苯基或溴基连接到甲硅烷氧基芳族衍生物的甲基上。 该试剂可以类似地连接到寡核苷酸探针。 通过离子信号（X）活化烷基化剂，其可以天然存在，或者可以通过引入盐（MX）引入含有靶分子的介质中。

公开(公告)号：US5831073A

公开(公告)日：1998-11-03

申请号：US603221

申请日：1996-02-20

申请人： Steven E. Rokita ,  Tianhu Li ,  Qingping Zeng

发明人： Steven E. Rokita ,  Tianhu Li ,  Qingping Zeng

IPC分类号： C07D207/404 ,  C07F7/18 ,  C07H19/04 ,  C07H21/00 ,  C07H23/00

CPC分类号： C07F7/1852 ,  C07D207/404 ,  C07F7/1856 ,  C07H21/00 ,  C07H23/00

摘要： A silyloxy aromatic derivative capable of alkylating a target biological molecule when activated by ionic strength. A sequence directed reagent may be constructed by conjugating a methyl silyloxy aromatic derivative to a hexamethylamino linker attached to either the 5' or 3' terminus of an oligonucleotide. Annealing this modified fragment of DNA to its complementary sequence allows for target modification subsequent to ionic activation. The product of this reaction is a covalent crosslink between the reagent and target strands resulting from an alkylation of DNA by the activated silyloxy aromatic derivative. In a preferred embodiment, a nitrophenyl or bromo group is attached to a methyl group of the silyloxy aromatic derivative. This reagent may be similarly linked to an oligonucleotide probe. Activation of the alkylating agent by an ionic signal (X) which may naturally occur, or may be introduced into the media containing the target molecule, such as by the introduction of a salt (MX).

摘要翻译： 当通过离子强度活化时，能够将靶生物分子烷基化的甲硅烷氧基芳族衍生物。 序列导向的试剂可以通过将甲基甲硅烷氧基芳族衍生物与连接到寡核苷酸的5'或3'末端的六甲基氨基接头共轭来构建。 将该修饰的DNA片段退火至其互补序列允许在离子活化后进行靶修饰。 该反应的产物是由活化的甲硅烷氧基芳族衍生物的DNA烷基化产生的试剂和靶链之间的共价交联。 在优选的实施方案中，硝基苯基或溴基连接到甲硅烷氧基芳族衍生物的甲基上。 该试剂可以类似地连接到寡核苷酸探针。 通过离子信号（X）活化烷基化剂，其可以天然存在，或者可以通过引入盐（MX）引入含有靶分子的介质中。

公开(公告)号：US5296350A

公开(公告)日：1994-03-22

申请号：US606463

申请日：1990-10-31

申请人： Steven E. Rokita ,  Tianhu Li

发明人： Steven E. Rokita ,  Tianhu Li

IPC分类号： C07F7/18 ,  C07H21/00 ,  C07H23/00 ,  C12Q1/68

CPC分类号： C07H21/00 ,  C07F7/1852 ,  C07F7/1856 ,  C07H23/00

摘要： A sequence directed reagent is constructed by conjugating a methyl silyloxy aromatic derivative to a hexamethylamino linker attached to either the 5' or 3' terminus of an oligonucleotide. Annealing this modified fragment of DNA to its complementary sequence allows for target modification subsequent to ionic activation. The product of this reaction is a covalent crosslink between the reagent and target strands resulting from an alkylation of DNA by the activated silyloxy aromatic derivative. In a preferred embodiment, a nitrophenyl group is attached to the methyl group of the silyloxy aromatic derivative. This reagent is similarly linked to an oligonucleotide probe. Activation of this probe linked alkylating agent by an ionic signal, (X) which may naturally occur, or may be introduced into the media containing the target molecule, such as by the introduction of a salt (MX).

摘要翻译： 通过将甲基甲硅烷氧基芳族衍生物与连接到寡核苷酸的5'或3'末端的六甲基氨基接头缀合来构建顺序导向的试剂。 将该修饰的DNA片段退火至其互补序列允许在离子活化后进行靶修饰。 该反应的产物是由活化的甲硅烷氧基芳族衍生物的DNA烷基化产生的试剂和靶链之间的共价交联。 在优选的实施方案中，硝基苯基与甲硅烷氧基芳族衍生物的甲基连接。 该试剂类似地与寡核苷酸探针连接。 通过离子信号（X）活化该探针连接的烷基化剂，例如通过引入盐（MX），可天然存在或可以引入含有靶分子的介质中。

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。

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。