5-[2-amino-6-(2-carboxyethylsulfanyl)pyrimidin-4-yl]-2,4-dimethylbenzoic acid tert-butyl ester | 1052647-40-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-[2-amino-6-(2-carboxyethylsulfanyl)pyrimidin-4-yl]-2,4-dimethylbenzoic acid tert-butyl ester
• 英文别名: 5-[2-amino-6-(2-carboxyethylsulfanyl)pyrimidin-4-yl]-2,4-dimethyl-benzoic acid tert-butyl ester；3-[2-amino-6-[2,4-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]pyrimidin-4-yl]sulfanylpropanoic acid
• CAS: 1052647-40-1
• 化学式: C₂₀H₂₅N₃O₄S
• 分子量: 403.502
• InChiKey: JYJHMSFUIIJRAH-UHFFFAOYSA-N

物化性质

• 沸点：
  630.0±65.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-[2-amino-6-(2-carboxyethylsulfanyl)pyrimidin-4-yl]-2,4-dimethylbenzoic acid tert-butyl ester 在 1-羟基苯并三唑 、 苯甲醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 CH5164840
  参考文献：
  名称：

  Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors

  摘要：

  Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors. CH5164840 showed high binding affinity for N-terminal Hsp90 alpha (K-d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC50 = 0.15 mu M, NCI-N87 IC50 = 0.066 mu M). CH5164840 displayed high oral bioavailability in mice (F = 70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition = 83%). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.100
• 作为产物：
  描述：

  2,4-二甲基苯甲酸 在 sodium periodate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 硫酸 、 碘 、 potassium acetate 、 乙酸酐 、 碳酸氢钠 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 、 溶剂黄146 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 47.17h， 生成 5-[2-amino-6-(2-carboxyethylsulfanyl)pyrimidin-4-yl]-2,4-dimethylbenzoic acid tert-butyl ester
  参考文献：
  名称：

  Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors

  摘要：

  Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors. CH5164840 showed high binding affinity for N-terminal Hsp90 alpha (K-d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC50 = 0.15 mu M, NCI-N87 IC50 = 0.066 mu M). CH5164840 displayed high oral bioavailability in mice (F = 70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition = 83%). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.100

文献信息

• Macrocyclic Compound
  申请人：Shimma Nobuo

  公开号：US20100056510A1

  公开（公告）日：2010-03-04

  The present invention provides a novel class of compounds that have the activity of inhibiting HSP90 enzyme and are useful as anti-cancer agents or such, and compounds that are useful as synthetic intermediates thereof. Specifically, the present invention provides compounds represented by the following formula (1), and pharmaceutically acceptable salts thereof: wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , L 1 , L 2 , and L 3 are as defined in the specification.

  本发明提供了一种新型化合物类，具有抑制HSP90酶活性的特性，可用作抗癌剂或其他用途，以及用作其合成中间体的化合物。具体而言，本发明提供了以下式（1）所表示的化合物及其药学上可接受的盐：其中，X、R1、R2、R3、R4、R5、R6、R7、L1、L2和L3如规范中所定义。
• Macrocyclic compound
  申请人：Shimma Nobuo

  公开号：US08362236B2

  公开（公告）日：2013-01-29

  The present invention provides a novel class of compounds that have the activity of inhibiting HSP90 enzyme and are useful as anti-cancer agents or such, and compounds that are useful as synthetic intermediates thereof. Specifically, the present invention provides compounds represented by the following formula (1), and pharmaceutically acceptable salts thereof: wherein X, R1, R2, R3, R4, R5, R6, R7, L1, L2, and L3 are as defined in the specification.

  本发明提供了一种新型化合物类别，具有抑制HSP90酶活性的作用，并可用作抗癌剂等，以及作为其合成中间体的化合物。具体而言，本发明提供以下式（1）所表示的化合物及其药学上可接受的盐：其中X，R1，R2，R3，R4，R5，R6，R7，L1，L2和L3如规范中所定义。
• MACROCYCLIC COMPOUND
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP2119718B1

  公开（公告）日：2012-04-11
• US8362236B2
  申请人：——

  公开号：US8362236B2

  公开（公告）日：2013-01-29
• Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors
  作者：Atsushi Suda、Hiroshi Koyano、Tadakatsu Hayase、Kihito Hada、Ken-ichi Kawasaki、Susumu Komiyama、Kiyoshi Hasegawa、Takaaki A. Fukami、Shigeo Sato、Takaaki Miura、Naomi Ono、Toshikazu Yamazaki、Ryoichi Saitoh、Nobuo Shimma、Yasuhiko Shiratori、Takuo Tsukuda

  DOI：10.1016/j.bmcl.2011.11.100

  日期：2012.1

  Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors. CH5164840 showed high binding affinity for N-terminal Hsp90 alpha (K-d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC50 = 0.15 mu M, NCI-N87 IC50 = 0.066 mu M). CH5164840 displayed high oral bioavailability in mice (F = 70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition = 83%). (C) 2011 Elsevier Ltd. All rights reserved.