2-[1-(2,2,2-Trifluoroethyl)piperidin-4-yl]ethyl methanesulfonate | 1396789-84-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-[1-(2,2,2-Trifluoroethyl)piperidin-4-yl]ethyl methanesulfonate
• 英文别名: 2-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]ethyl methanesulfonate
• CAS: 1396789-84-6
• 化学式: C₁₀H₁₈F₃NO₃S
• 分子量: 289.319
• InChiKey: WDBBLNLHEABYOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-(7-bromo-2,3-dihydro-benzo[1,4]dioxin-6-ylsulfanyl)adenine 、 2-[1-(2,2,2-Trifluoroethyl)piperidin-4-yl]ethyl methanesulfonate 在 2-叔丁基-1,1,3,3-四甲基胍 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(2,2,2-trifluoroethyl)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
• 作为产物：
  描述：

  4-哌啶乙醇 在 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 2-[1-(2,2,2-Trifluoroethyl)piperidin-4-yl]ethyl methanesulfonate
  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

• Discovery of (2<i>S</i>)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9<i>H</i>-purin-9-yl}ethyl)piperidin-1-yl]-2-hydroxypropan-1-one (MPC-3100), a Purine-Based Hsp90 Inhibitor
  作者：Se-Ho Kim、Ashok Bajji、Rajendra Tangallapally、Benjamin Markovitz、Richard Trovato、Mark Shenderovich、Vijay Baichwal、Paul Bartel、Daniel Cimbora、Rena McKinnon、Rosann Robinson、Damon Papac、Daniel Wettstein、Robert Carlson、Kraig M. Yager

  DOI：10.1021/jm3004619

  日期：2012.9.13

  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.