8-((6-bromobenzo[d][1,3]dioxol-5-yl)thio)-9-(2-(piperidin-4-yl)ethyl)-9H-purin-6-amine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 8-((6-bromobenzo[d][1,3]dioxol-5-yl)thio)-9-(2-(piperidin-4-yl)ethyl)-9H-purin-6-amine
• 英文别名: 8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9-(2-piperidin-4-ylethyl)-9H-purin-6-amine；8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-(2-piperidin-4-ylethyl)purin-6-amine
• 化学式: C₁₉H₂₁BrN₆O₂S
• 分子量: 477.385
• InChiKey: ZJDQEUGFIISUAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-((6-bromobenzo[d][1,3]dioxol-5-yl)thio)-9-(2-(piperidin-4-yl)ethyl)-9H-purin-6-amine 在 silver trifluoromethanesulfonate 、 三乙胺 、 silver carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 58.0h， 生成 (2S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-yl β-D-glucopyranosiduronic acid triethylamine
  参考文献：
  名称：

  [EN] PRODRUGS OF THERAPEUTIC COMPOUNDS
  [FR] PROMÉDICAMENTS DE COMPOSÉS THÉRAPEUTIQUES

  摘要：

  本发明提供了化合物、药物组合物和包含这些化合物的药物，以及在治疗癌症等疾病和疾病的方法中使用这些化合物、组合物和药物。

  公开号：

  WO2012148550A1
• 作为产物：
  描述：

  4-哌啶乙醇 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 caesium carbonate 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 8-((6-bromobenzo[d][1,3]dioxol-5-yl)thio)-9-(2-(piperidin-4-yl)ethyl)-9H-purin-6-amine
  参考文献：
  名称：

  Discovery of (2S)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-hydroxypropan-1-one (MPC-3100), a Purine-Based Hsp90 Inhibitor

  摘要：

  Modulation of Hsp90 (heat shock protein 90) function has been recognized as an attractive approach for cancer treatment, since many cancer cells depend on Hsp90 to maintain cellular homeostasis. This has spurred the search for small-molecule Hsp90 inhibitors. Here we describe our lead optimization studies centered on the purine-based Hsp90 inhibitor 28a containing a piperidine moiety at the purine N9 position. In this study, key SAR was established for the piperidine N-substituent and for the congeners of the 1,3-benzodioxole at C8. These efforts led to the identification of orally bioavailable 28g that exhibits good in vitro profiles and a characteristic molecular biomarker signature of Hsp90 inhibition both in vitro and in vivo. Favorable pharmacokinetic properties along with significant antitumor effects in multiple human cancer xenograft models led to the selection of 28g (MPC-3100) as a clinical candidate.

  DOI：

  10.1021/jm3004619

文献信息

• [EN] TARGETED THERAPEUTICS<br/>[FR] THÉRAPEUTIQUE CIBLÉE
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2015038649A1

  公开（公告）日：2015-03-19

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供了包括与将效应子导向至感兴趣的生物靶点的结合基团共轭的药理化合物。同样，本发明提供了包括这些化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。这些化合物可以被描述为蛋白质相互作用结合基团-药物共轭（SDC-TRAP）化合物，其中包括蛋白质相互作用结合基团和效应子。例如，在针对治疗癌症的某些实施方式中，SDC-TRAP可以包括Hsp90抑制剂共轭到细胞毒性药剂作为效应子。
• [EN] THERAPEUTIC COMPOUNDS AND THEIR USE IN TREATING DISEASES AND DISORDERS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES ET DE TROUBLES
  申请人：MYRIAD GENETICS INC

  公开号：WO2009065035A1

  公开（公告）日：2009-05-22

  The invention provides novel therapeutic compounds, pharmaceutical compositions comprising these compounds, and methods for using these compounds and compositions to treat diseases and disorders, such as cancer.

  这项发明提供了新型治疗化合物，包括这些化合物的药物组合物，以及使用这些化合物和组合物治疗疾病和疾病的方法，如癌症。
• THERAPEUTIC COMPOUNDS AND THEIR USE IN CANCER
  申请人：Bajji C. Ashok

  公开号：US20070299258A1

  公开（公告）日：2007-12-27

  The invention relates to compounds of Formulae I-III and their therapeutic uses.

  这项发明涉及到I-III式化合物及其治疗用途。
• Therapeutic compounds and their use in cancer
  申请人：Myriad Pharmaceuticals, Inc.

  公开号：US07595401B2

  公开（公告）日：2009-09-29

  The invention relates to compounds of Formula I and their therapeutic uses, wherein substituent A is chosen from a substituted or unsubstituted aryl, heteroaryl, heterocyclic, or carboxylic group, B is chosen from a substituted or unsubstituted piperidine, homopiperidine, piperazine, pyrrolidine or azetidine group, R1 is chosen from hydro, alkyl, aryl, heteroaryl amino and halo, and L1 and L2 are as defined in the specification.

  本发明涉及I式化合物及其治疗用途，其中取代基A选择自取代或未取代的芳基、杂芳基、杂环基或羧基，取代基B选择自取代或未取代的哌啶基、同哌啶基、吡咯烷基或氮杂环基，R1选择自氢、烷基、芳基、杂芳基氨基和卤素，L1和L2如说明书所定义。
• Purine-core inhibitors of HSP90 and their use in treating cancer
  申请人：Bajji Ashok C.

  公开号：US08476285B2

  公开（公告）日：2013-07-02

  The invention relates to compounds of Formulae I-III: and therapeutic uses thereof, wherein A is chosen from a substituted or unsubstituted aryl, heteroaryl, heterocyclic, or carbocyclic group; B is chosen from a substituted or unsubstituted piperidine, homopiperidine, piperazine, pyrrolidine or azetidine group; R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, or halo; and L1, L2, are as defined herein.

  本发明涉及I-III式化合物及其治疗用途，其中A选择取代或未取代的芳基，杂芳基，杂环或碳环基；B选择取代或未取代的哌啶，同哌啶，吡咯烷或氮杂环基；R1选择氢、烷基、芳基、杂芳基、氨基或卤素；L1，L2定义如本文所述。