6-[(6-amino-9H-purin-8-yl)thio]-1,3-benzodioxole-5-carbonitrile | 958026-14-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-[(6-amino-9H-purin-8-yl)thio]-1,3-benzodioxole-5-carbonitrile
• 英文别名: 6-[(6-amino-7H-purin-8-yl)sulfanyl]-1,3-benzodioxole-5-carbonitrile
• CAS: 958026-14-7
• 化学式: C₁₃H₈N₆O₂S
• 分子量: 312.312
• InChiKey: AXLIAXNIJMDWIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(1-formyl-4-piperidyl)ethyl 4-methylbenzenesulfonate 、 6-[(6-amino-9H-purin-8-yl)thio]-1,3-benzodioxole-5-carbonitrile 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， 以22%的产率得到6-[6-Amino-9-[2-(1-formylpiperidin-4-yl)ethyl]purin-8-yl]sulfanyl-1,3-benzodioxole-5-carbonitrile
  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：

  6-溴-1,3-苯并二氧戊环-5-甲腈 、 8-巯基腺嘌呤 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以15%的产率得到6-[(6-amino-9H-purin-8-yl)thio]-1,3-benzodioxole-5-carbonitrile
  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 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。
• 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
• US7595401B2
  申请人：——

  公开号：US7595401B2

  公开（公告）日：2009-09-29