(2S)-1-[4-[2-[6-氨基-8-[(6-溴-1,3-苯并二氧戊环-5-基)硫基]-9H-嘌呤-9-基]乙基]-1-哌啶基]-2-羟基-1-丙酮 | 958025-66-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: (2S)-1-[4-[2-[6-氨基-8-[(6-溴-1,3-苯并二氧戊环-5-基)硫基]-9H-嘌呤-9-基]乙基]-1-哌啶基]-2-羟基-1-丙酮
• 中文别名: (S)-1-(4-(2-(6-氨基-8-((6-溴苯并[d][1,3]二氧代l-5-基)硫代)-9H-嘌呤-9-基)乙基)哌啶-1-基)-2-羟基丙烷-1-酮
• 英文名称: MPC-3100
• 英文别名: (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；(S)-1-(4-(2-(6-Amino-8-((6-bromobenzo[d][1,3]dioxol-5-yl)thio)-9H-purin-9-yl)ethyl)piperidin-1-yl)-2-hydroxypropan-1-one；(2S)-1-[4-[2-[6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]ethyl]piperidin-1-yl]-2-hydroxypropan-1-one
• CAS: 958025-66-6
• 化学式: C₂₂H₂₅BrN₆O₄S
• 分子量: 549.448
• InChiKey: CVBWTNHDKVVFMI-LBPRGKRZSA-N

物化性质

• 沸点：
  772.4±70.0 °C(Predicted)
• 密度：
  1.77±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 储存条件：
  -20°C，密封保存，置于干燥处。

制备方法与用途

MPC-3100是一种口服生物利用的合成第二代Hsp90小分子抑制剂，具有潜在的抗肿瘤活性。

反应信息

• 作为反应物：
  描述：

  (2S)-1-[4-[2-[6-氨基-8-[(6-溴-1,3-苯并二氧戊环-5-基)硫基]-9H-嘌呤-9-基]乙基]-1-哌啶基]-2-羟基-1-丙酮 在 copper(II) acetate monohydrate 、 溶剂黄146 、 锌 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 、 乙酰丙酮 为溶剂， 反应 54.0h， 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 dihydrogen phosphate ammonium
  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 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 (2S)-1-[4-[2-[6-氨基-8-[(6-溴-1,3-苯并二氧戊环-5-基)硫基]-9H-嘌呤-9-基]乙基]-1-哌啶基]-2-羟基-1-丙酮
  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

• 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。
• TARGETED THERAPEUTICS
  申请人：Chimmanamada Dinesh U.

  公开号：US20140079636A1

  公开（公告）日：2014-03-20

  The present invention provides pharmacological compounds including an effector moiety conjugated to an 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.

  本发明提供了药理化合物，包括将效应器基团偶联到结合基团上，以将效应器基团定向到感兴趣的生物靶点。同样，本发明提供了包括该化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。该化合物可以被描述为蛋白质相互作用的结合基团-药物偶联物（SDC-TRAP）化合物，包括蛋白质相互作用的结合基团和效应器基团。例如，在治疗癌症的某些实施方案中，SDC-TRAP可以包括Hsp90抑制剂与细胞毒素剂作为效应器基团的偶联物。
• Methods of treating a metabolic syndrome by modulating heat shock protein (HSP) 90-beta
  申请人：Berg LLC

  公开号：US10023864B2

  公开（公告）日：2018-07-17

  The invention provides HSP90β inhibitors comprising an antisense oligonucleotide targeting HSP90β, pharmaceutical compositions comprising said inhibitors and methods of treatment of a metabolic syndrome by administering said HSP90β inhibitors to a subject in need thereof. The antisense oligonucleotides may be targeted to skeletal muscle.

  本发明提供了由靶向 HSP90β 的反义寡核苷酸组成的 HSP90β 抑制剂、由所述抑制剂组成的药物组合物以及通过向有需要的受试者施用所述 HSP90β 抑制剂来治疗代谢综合征的方法。反义寡核苷酸可靶向骨骼肌。
• Targeted therapeutics
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：US10376598B2

  公开（公告）日：2019-08-13

  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.

  本发明提供的药理化合物包括与结合基团共轭的效应分子，该结合基团可将效应分子导向感兴趣的生物靶标。同样，本发明还提供了包括这些化合物的组合物、试剂盒和方法（如治疗、诊断和成像）。这些化合物可被描述为蛋白质相互作用结合分子-药物共轭物（SDC-TRAP）化合物，其中包括蛋白质相互作用结合分子和效应分子。例如，在某些用于治疗癌症的实施方案中，SDC-TRAP 可包括与细胞毒剂共轭的 Hsp90 抑制剂作为效应分子。
• Compositions to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
  申请人：Race Oncology Ltd.

  公开号：US10548876B2

  公开（公告）日：2020-02-04

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.

  本发明描述了通过提高单一疗法的疗效或减少副作用来改善以前因治疗效果不理想而受到限制的治疗剂的疗效的方法和组合物。这些方法和组合物尤其适用于双蒽或其衍生物、类似物或原药。