2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-yl]-2-oxoethanol | 958025-74-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-yl]-2-oxoethanol
• 英文别名: 2-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-oxoethanol；1-[4-[2-[6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]ethyl]piperidin-1-yl]-2-hydroxyethanone
• CAS: 958025-74-6
• 化学式: C₂₁H₂₃BrN₆O₄S
• 分子量: 535.421
• InChiKey: SCDSEGOZSQRZEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-哌啶乙醇 在 2-叔丁基-1,1,3,3-四甲基胍 、 1-羟基苯并三唑 、 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 38.0h， 生成 2-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-yl]-2-oxoethanol
  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] 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。
• 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。
• US7595401B2
  申请人：——

  公开号：US7595401B2

  公开（公告）日：2009-09-29
• US8476285B2
  申请人：——

  公开号：US8476285B2

  公开（公告）日：2013-07-02
• [EN] THERAPEUTIC COMPOUNDS AND THEIR USE IN CANCER<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ET LEUR UTILISATION CONTRE LE CANCER
  申请人：MYRIAD GENETICS INC

  公开号：WO2007134298A2

  公开（公告）日：2007-11-22

  [EN] The invention relates to compounds of Formulae I-III and their therapeutic uses.
  [FR] La présente invention concerne des composés répondant aux formules (I) à (III) et leurs utilisations thérapeutiques.