4-({(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} oxy)-4-oxobutanoic acid sodium salt | 1404473-59-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-({(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} oxy)-4-oxobutanoic acid sodium salt
• 英文别名: sodium;4-[(2S)-1-[4-[2-[6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]ethyl]piperidin-1-yl]-1-oxopropan-2-yl]oxy-4-oxobutanoate
• CAS: 1404473-59-1
• 化学式: C₂₆H₂₈BrN₆O₇S*Na
• 分子量: 671.504
• InChiKey: DOSOXJFYPZAUFL-UQKRIMTDSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.85
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  200
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4-(2-溴乙基)哌啶-1-羧酸叔丁酯 在 4-二甲氨基吡啶 溴 、 sodium methylate 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 silver carbonate 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 46.0h， 生成 4-({(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} oxy)-4-oxobutanoic acid sodium salt
  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

文献信息

• Discovery of an l-alanine ester prodrug of the Hsp90 inhibitor, MPC-3100
  作者：Se-Ho Kim、Rajendra Tangallapally、In Chul Kim、Richard Trovato、Daniel Parker、J. Scott Patton、Leslie Reeves、Chad Bradford、Daniel Wettstein、Vijay Baichwal、Damon Papac、Ashok Bajji、Robert Carlson、Kraig M. Yager

  DOI：10.1016/j.bmcl.2015.09.053

  日期：2015.11

  Various types of Hsp90 inhibitors have been and continue to undergo clinical investigation. One development candidate is the purine-based, synthetic Hsp90 inhibitor 1 (MPC-3100), which successfully completed a phase I clinical study. However, further clinical development of 1 was hindered by poor solubility and consequent formulation issues and promoted development of a more water soluble prodrug. Towards this end, numerous pro-moieties were explored in vitro and in vivo. These studies resulted in identification of L-alanine ester mesylate, 2i (MPC-0767), which exhibited improved aqueous solubility, adequate chemical stability, and rapid bioconversion without the need for solubilizing excipients. Based on improved physical characteristics and favorable PK and PD profiles, 2i mesylate was selected for further development. A convergent, scalable, chromatography-free synthesis for 2i mesylate was developed to support further clinical evaluation. (C) 2015 Elsevier Ltd. All rights reserved.
• [EN] PRODRUGS OF THERAPEUTIC COMPOUNDS<br/>[FR] PROMÉDICAMENTS DE COMPOSÉS THÉRAPEUTIQUES
  申请人：MYREXIS INC

  公开号：WO2012148550A1

  公开（公告）日：2012-11-01

  The present invention provides compounds, pharmaceutical compositions and medicaments comprising such compounds, and the use of these compounds, compositions, and medicaments in methods of treating diseases and disorders such as cancers.

  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。