2-amino-4-chloro-5-isobutyl-8-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7,8-dihydro-5H-pteridin-6-one | 1165805-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 2-amino-4-chloro-5-isobutyl-8-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7,8-dihydro-5H-pteridin-6-one
• 英文别名: 2-amino-4-chloro-8-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-5-(2-methylpropyl)-7H-pteridin-6-one
• CAS: 1165805-34-4
• 化学式: C₁₉H₂₅ClN₆O₂
• 分子量: 404.9
• InChiKey: MWTQHKCGQFZKSU-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：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  97.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-amino-4-chloro-5-isobutyl-8-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7,8-dihydro-5H-pteridin-6-one 在 甲醇 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 48.0h， 以70%的产率得到2-amino-4-methoxy-8-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-5-(2-methylpropyl)-7H-pteridin-6-one
  参考文献：
  名称：

  Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors

  摘要：

  A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 mu M. The structure-activity relationship (SAR) of this series is reported here. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.03.074
• 作为产物：
  描述：

  2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-one 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-amino-4-chloro-5-isobutyl-8-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7,8-dihydro-5H-pteridin-6-one
  参考文献：
  名称：

  Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors

  摘要：

  A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 mu M. The structure-activity relationship (SAR) of this series is reported here. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.03.074

文献信息

• [EN] BIOACTIVE COMPOUNDS FOR TREATMENT OF CANCER AND NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS BIOACTIFS POUR LE TRAITEMENT DU CANCER ET DES MALADIES NEURODÉGÉNÉRATIVES
  申请人：PONIARD PHARMACEUTICALS INC

  公开号：WO2009139834A1

  公开（公告）日：2009-11-19

  The invention provides bioactive compounds for the treatment of various malconditions such as cancer and neurodegenerative diseases including Alzheimer's disease. The chemical compounds as disclosed herein are found to show bioactivity in bioassays related to these conditions. Pharmaceutical compositions, combinations and methods of synthesis are provided, as are methods of using the compound, compositions and combinations in the treatment of the diseases.

  这项发明提供了用于治疗各种恶性疾病，如癌症和包括阿尔茨海默病在内的神经退行性疾病的生物活性化合物。本文所披露的化合物在与这些疾病相关的生物测定中显示出生物活性。提供了药物组合物、组合物和合成方法，以及使用该化合物、组合物和组合物治疗这些疾病的方法。
• BIOACTIVE COMPOUNDS FOR TREATMENT OF CANCER AND NEURODEGENERATIVE DISEASES
  申请人：Sun Connie L.

  公开号：US20110124634A1

  公开（公告）日：2011-05-26

  The invention provides bioactive compounds for the treatment of various malconditions such as cancer and neurodegenerative diseases including Alzheimer's disease. The chemical compounds as disclosed herein are found to show bioactivity in bioassays related to these conditions. Pharmaceutical compositions, combinations and methods of synthesis are provided, as are methods of using the compound, compositions and combinations in the treatment of the diseases.

  本发明提供了用于治疗各种恶性疾病和神经退行性疾病，包括阿尔茨海默病的生物活性化合物。本文所披露的化学化合物被发现在与这些疾病相关的生物测定中表现出生物活性。提供了制药组合物、组合物的合成方法和使用该化合物、组合物和组合物治疗这些疾病的方法。
• Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones as potent and selective Hsp90 inhibitors
  作者：Xiaoyuan Li、Ellyn Shocron、Aimin Song、Neela Patel、Connie L. Sun

  DOI：10.1016/j.bmcl.2009.03.074

  日期：2009.5

  A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7,8-dihydropteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 mu M. The structure-activity relationship (SAR) of this series is reported here. (C) 2009 Published by Elsevier Ltd.