9-butyl-8-(3-methoxybenzyl)-9H-purin-6-ylamine | 521308-67-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-butyl-8-(3-methoxybenzyl)-9H-purin-6-ylamine
• 英文别名: 9-Butyl-8-(3-methoxybenzyl)-9H-purin-6-amine；9-butyl-8-[(3-methoxyphenyl)methyl]purin-6-amine
• CAS: 521308-67-8
• 化学式: C₁₇H₂₁N₅O
• 分子量: 311.387
• InChiKey: BWLWUGBHOXIUBP-UHFFFAOYSA-N

物化性质

• 熔点：
  163-165 °C
• 沸点：
  554.3±45.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-butyl-8-(3-methoxybenzyl)-9H-purin-6-ylamine 在 N-碘代丁二酰亚胺 、 溶剂黄146 作用下， 反应 16.0h， 生成 9-Butyl-8-(2-iodo-5-methoxy-benzyl)-9H-purin-6-ylamine
  参考文献：
  名称：

  Orally Active Purine-Based Inhibitors of the Heat Shock Protein 90

  摘要：

  Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble and consequently have unacceptably low oral bioavailabilities. We now report that water-solubility can be achieved by inserting an amino functionality in the N(9) side chain. This results in compounds that are potent, soluble in aqueous media, and orally bioavailable. In an HER-2 degradation assay, the highest potency was achieved with the neopentylamine 42 (HER-2 IC50 = 90 nM). In a murine tumor xenograft model (using the gastric cancer cell line N87), the H3PO4 salts of the amines 38, 39, and 42 induced tumor growth inhibition when administered orally at 200 mg/kg/day. The amines 38, 39, and 42 are the first Hsp90 inhibitors shown to inhibit tumor growth upon oral dosage.

  DOI：

  10.1021/jm0503087
• 作为产物：
  描述：

  3-甲氧基苯基乙酰氯 在 sodium methylate 、 caesium carbonate 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 21.0h， 生成 9-butyl-8-(3-methoxybenzyl)-9H-purin-6-ylamine
  参考文献：
  名称：

  Orally Active Purine-Based Inhibitors of the Heat Shock Protein 90

  摘要：

  Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble and consequently have unacceptably low oral bioavailabilities. We now report that water-solubility can be achieved by inserting an amino functionality in the N(9) side chain. This results in compounds that are potent, soluble in aqueous media, and orally bioavailable. In an HER-2 degradation assay, the highest potency was achieved with the neopentylamine 42 (HER-2 IC50 = 90 nM). In a murine tumor xenograft model (using the gastric cancer cell line N87), the H3PO4 salts of the amines 38, 39, and 42 induced tumor growth inhibition when administered orally at 200 mg/kg/day. The amines 38, 39, and 42 are the first Hsp90 inhibitors shown to inhibit tumor growth upon oral dosage.

  DOI：

  10.1021/jm0503087

文献信息

• Purine analogs having hsp90-inhibiting activity
  申请人：Kasibhatla Rao Srinivas

  公开号：US20050049263A1

  公开（公告）日：2005-03-03

  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.

  本发明描述了新型嘌呤化合物及其互变异构体以及其药学上可接受的盐，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。
• Purine analogs having HSP90-inhibiting activity
  申请人：Conforma Therapeutics Corporation

  公开号：US07241890B2

  公开（公告）日：2007-07-10

  Novel purine compounds of Formula I. and tautomers, pharmaceutically acceptable salts, and prodrugs thereof, wherein X is S, S(O), or S(O)2; and O is selected from alkyl, cycloalkyl, arylalkyl, aryl, heteroaryl, and heterocyclic, all optionally substituted, are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same.

  本发明涉及一种新型嘌呤化合物I及其互变异构体、药学上可接受的盐和前药。其中，X为S、S(O)或S(O)2; O选自烷基、环烷基、芳基烷基、芳基、杂环芳基和杂环，均可选择性地被取代。同时，本发明还涉及含有该化合物的制药组合物、包括该化合物的复合物，如HSP90复合物，以及使用它们的方法。
• 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。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• Adenine derived inhibitors of the molecular chaperone HSP90—SAR explained through multiple X-ray structures
  作者：Brian Dymock、Xavier Barril、Mandy Beswick、Adam Collier、Nicholas Davies、Martin Drysdale、Alexandra Fink、Christophe Fromont、Roderick E. Hubbard、Andrew Massey、Allan Surgenor、Lisa Wright

  DOI：10.1016/j.bmcl.2003.11.011

  日期：2004.1

  Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.