methanesulfonic acid 2-[6-amino-8-(7-chlorobenzothiazol-2-ylsulfanyl)-purin-9-yl]-ethyl ester | 908355-85-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: methanesulfonic acid 2-[6-amino-8-(7-chlorobenzothiazol-2-ylsulfanyl)-purin-9-yl]-ethyl ester
• 英文别名: Methanesulfonic acid 2-[6-amino-8-(7-chloro-benzothiazol-2-ylsulfanyl)-purin-9-yl]-ethyl ester；2-[6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]purin-9-yl]ethyl methanesulfonate
• CAS: 908355-85-1
• 化学式: C₁₅H₁₃ClN₆O₃S₃
• 分子量: 456.958
• InChiKey: YZZKCJBGFADBST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  188
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methanesulfonic acid 2-[6-amino-8-(7-chlorobenzothiazol-2-ylsulfanyl)-purin-9-yl]-ethyl ester 、 特戊胺 在 amine 、 silica gel 、 methanol-dichloromethane 作用下， 反应 16.0h， 以to give 8-(7-chloro-benzothiazol-2-ylsulfanyl)-9-[2-(2,2-dimethyl-propylamino)-ethyl]-9H-purin-6-yl amine (30 mg, 0.067 mmol) as a white powder with 30.5% yield的产率得到8-(7-chlorobenzothiazol-2-ylsulfanyl)-9-[2-(2,2-dimethylpropylamino)-ethyl]-9H-purin-6-ylamine
  参考文献：
  名称：

  Orally Active Purine-Based Inhibitors of Heat Shock Protein 90

  摘要：

  本发明描述了新型嘌呤化合物及其互变异构体和药学上可接受的盐，以及包含它们的制药组合物、包含它们的复合物（例如HSP90复合物）和使用它们的方法。使用本发明的新型嘌呤化合物、互变异构体和药学上可接受的盐的方法包括在抑制热休克蛋白90（HSP90）中使用它们，从而治疗或预防HSP90依赖性疾病，例如增生性疾病如乳腺癌。

  公开号：

  US20070129334A1
• 作为产物：
  描述：

  acetic acid 2-(6-aminopurin-9-yl)-ethyl ester 在 potassium tert-butylate 、 氨 、 溴 、 sodium acetate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.92h， 生成 methanesulfonic acid 2-[6-amino-8-(7-chlorobenzothiazol-2-ylsulfanyl)-purin-9-yl]-ethyl ester
  参考文献：
  名称：

  7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors

  摘要：

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).

  DOI：

  10.1021/jm051146h

文献信息

• Orally Active Purine-Based Inhibitors of Heat Shock Protein 90
  申请人：Kasibhatla R. Srinivas

  公开号：US20070129334A1

  公开（公告）日：2007-06-07

  Novel purine compounds and tautomers and pharmaceutically acceptable salts thereof are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same. Methods of using the novel purine compounds of the invention, and tautomers and pharmaceutically acceptable salts thereof, include their use in inhibiting heat shock protein 90's (HSP90's) to thereby treat or prevent HSP90-dependent diseases, e.g., proliferative disorders such as breast cancer.

  本发明描述了新型嘌呤化合物及其互变异构体和药学上可接受的盐，以及包含它们的制药组合物、包含它们的复合物（例如HSP90复合物）和使用它们的方法。使用本发明的新型嘌呤化合物、互变异构体和药学上可接受的盐的方法包括在抑制热休克蛋白90（HSP90）中使用它们，从而治疗或预防HSP90依赖性疾病，例如增生性疾病如乳腺癌。
• 7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors
  作者：Lin Zhang、Junhua Fan、Khang Vu、Kevin Hong、Jean-Yves Le Brazidec、Jiandong Shi、Marco Biamonte、David J. Busch、Rachel E. Lough、Roy Grecko、Yingqing Ran、John L. Sensintaffar、Adeela Kamal、Karen Lundgren、Francis J. Burrows、Robert Mansfield、Gregg A. Timony、Edgar H. Ulm、Srinivas R. Kasibhatla、Marcus F. Boehm

  DOI：10.1021/jm051146h

  日期：2006.8.1

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).