2-(1-formyl-4-piperidyl)ethyl 4-methylbenzenesulfonate | 1156468-26-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(1-formyl-4-piperidyl)ethyl 4-methylbenzenesulfonate
• 英文别名: 2-(1-formylpiperidine-4-yl)ethyl-4-methylbenzenesulfonate；2-(1-formylpiperidin-4-yl)ethyl 4-methylbenzenesulfonate
• CAS: 1156468-26-6
• 化学式: C₁₅H₂₁NO₄S
• 分子量: 311.402
• InChiKey: OQUNAOJFZMCYRK-UHFFFAOYSA-N

物化性质

• 沸点：
  497.8±18.0 °C(predicted)
• 密度：
  1.243±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-formyl-4-piperidyl)ethyl 4-methylbenzenesulfonate 在 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 4-(2-{6-Amino-8-[(7-bromo-2,3-dihydro-1,4-benzodioxin-6-yl)thio]-9H-purin-9-yl}ethyl)piperidine-1-carbaldehyde
  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 4-二甲氨基吡啶 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 2-(1-formyl-4-piperidyl)ethyl 4-methylbenzenesulfonate
  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] 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 uses thereof
  申请人：Myrexis, Inc.

  公开号：US08017780B1

  公开（公告）日：2011-09-13

  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.

  本发明提供了新型的治疗化合物，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癌症等疾病和疾病的方法。
• Therapeutic Compounds and Their Use in Treating Diseases and Disorders
  申请人：Bajji Ashok C.

  公开号：US20100292255A1

  公开（公告）日：2010-11-18

  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.

  该发明提供了新型治疗化合物、包含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，例如癌症。
• THERAPEUTIC COMPOUNDS AND THEIR USE IN TREATING DISEASES AND DISORDERS
  申请人：Myriad Pharmaceuticals, Inc.

  公开号：EP2219448A1

  公开（公告）日：2010-08-25
• US8017780B1
  申请人：——

  公开号：US8017780B1

  公开（公告）日：2011-09-13