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    Synthesis of triazole compounds that modulate HSP90 activity
    1.
    发明申请
    Synthesis of triazole compounds that modulate HSP90 activity 审中-公开
    合成调节HSP90活性的三唑化合物

    公开(公告)号：US20080125587A1

    公开(公告)日：2008-05-29

    申请号：US11807333

    申请日：2007-05-25

    申请人： Dinesh U. Chimmanamada ,  Chi-Wan Lee ,  David James ,  Shijie Zhang ,  Weiwen Ying ,  Junghyun Chae ,  Teresa Przewloka

    发明人： Dinesh U. Chimmanamada ,  Chi-Wan Lee ,  David James ,  Shijie Zhang ,  Weiwen Ying ,  Junghyun Chae ,  Teresa Przewloka

    IPC分类号： C07D249/12 ,  C07D407/02 ,  C07D403/02 ,  C07D401/02 ,  C07D401/04 ,  C07D403/10 ,  C07D417/02 ,  C07D487/04 ,  C07D413/12 ,  C07D413/02

    CPC分类号： C07D403/04 ,  C07D249/12 ,  C07D249/14 ,  C07D401/04 ,  C07D401/10 ,  C07D403/10 ,  C07D413/04 ,  C07D417/04

    摘要： The present invention provides novel methods of preparing triazole compounds which inhibit the activity of Hsp90. One embodiment of the invention is directed to methods for preparing a triazole compound represented by the following Structural Formula: or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof, comprising the steps of: a) reacting an amide represented by the following Structural Formula: with a thionation reagent to form a thioamide; b) reacting the thioamide of step a) with hydrazine to form a hydrazonamide; c) reacting the hydrazonamide of step b) with a carbonylation or a thiocarbonylation reagent.In one embodiment, the present invention is a method of synthesis of a compound of formula (IA) or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof, comprising reacting a compound of formula (IIA) with an oxidizing agent, thereby producing a compound of formula (IA).The present invention is also directed to a method of preparing a compound or a tautomer thereof represented by the following Structural Formula: or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof. The method comprises the step of reacting a first starting compound represented by the following Structural Formula: in the presence of a mercuric salt, with a second starting compound represented by the following Structural Formula:

    摘要翻译： 本发明提供抑制Hsp90活性的三唑化合物的新方法。 本发明的一个实施方案涉及制备由以下结构式表示的三唑化合物或互变异构体，药学上可接受的盐，溶剂化物或包合物或其前药的方法，其包括以下步骤：a）使酰胺 由以下结构式表示：用硫化试剂形成硫代酰胺; b）使步骤a）的硫代酰胺与肼反应形成腙酰胺; c）使步骤b）的腙与羰基化或硫代羰基化试剂反应。 在一个实施方案中，本发明是合成式（IA）化合物或互变异构体，其药学上可接受的盐，溶剂化物或包合物或其前药的方法，包括使式（IIA）化合物与 氧化剂，从而制备式（IA）化合物。 本发明还涉及制备由以下结构式表示的化合物或其互变异构体的方法：或其互变异构体，药学上可接受的盐，溶剂化物或包合物或其前药。 该方法包括使由以下结构式表示的第一起始化合物在汞盐存在下与由以下结构式表示的第二起始化合物反应的步骤：