4-amino-6-{7-chloro-3-oxatricyclo[7.3.1.0^5,13]trideca-1(13),5,7,9,11-pentaen-8-yl}-1,3,5-triazine-2-thiol | 959762-95-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-amino-6-{7-chloro-3-oxatricyclo[7.3.1.0^5,13]trideca-1(13),5,7,9,11-pentaen-8-yl}-1,3,5-triazine-2-thiol
• 英文别名: 4-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-2-amino-[1,3,5]triazine-6-thiol；4-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-[1,3,5]triazine-2-thiol；2-amino-6-(7-chloro-3-oxatricyclo[7.3.1.05,13]trideca-1(13),5,7,9,11-pentaen-8-yl)-1H-1,3,5-triazine-4-thione
• CAS: 959762-95-9
• 化学式: C₁₅H₁₁ClN₄OS
• 分子量: 330.798
• InChiKey: JAKBHLVNIWPWBM-UHFFFAOYSA-N

物化性质

• 沸点：
  553.5±60.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-amino-6-{7-chloro-3-oxatricyclo[7.3.1.0^5,13]trideca-1(13),5,7,9,11-pentaen-8-yl}-1,3,5-triazine-2-thiol 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-[(4-amino-6-{7-chloro-3-oxatricyclo[7.3.1.0^5,13]trideca-1(13),5,7,9,11-pentaen-8-yl}-1,3,5-triazin-2-yl)sulfanyl]propanoic acid
  参考文献：
  名称：

  HSP90 INHIBITOR

  摘要：

  公开号：

  EP2036895B1
• 作为产物：
  描述：

  8-bromo-7-nitro-3-oxatricyclo[7.3.1.0^5,13]trideca-1(13),5,7,9,11-pentaene 在 亚硝酸特丁酯 、 sodium dithionite 、 乙醇 、 三甲基铝 、 氯化铵 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 copper(l) chloride 、 potassium thioacetate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 54.0h， 生成 4-amino-6-{7-chloro-3-oxatricyclo[7.3.1.0^5,13]trideca-1(13),5,7,9,11-pentaen-8-yl}-1,3,5-triazine-2-thiol
  参考文献：
  名称：

  Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazines as novel Hsp90 inhibitors

  摘要：

  A novel series of 2-amino-1,3,5-triazines bearing a tricyclic moiety as heat shock protein 90 (Hsp90) inhibitors is described. Molecular design was performed using X-ray cocrystal structures of the lead compound CH5015765 and natural Hsp90 inhibitor geldanamycin with Hsp90. We optimized affinity to Hsp90, in vitro cell growth inhibitory activity, water solubility, and liver microsomal stability of inhibitors and identified CH5138303. This compound showed high binding affinity for N-terminal Hsp90 alpha (K-d = 0.52 nM) and strong in vitro cell growth inhibition against human cancer cell lines (HCT116 IC50 = 0.098 mu M, NCI-N87 IC50 = 0.066 mu M) and also displayed high oral bioavailability in mice (F = 44.0%) and potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model (tumor growth inhibition = 136%). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.036

文献信息

• HSP90 Inhibitor
  申请人：Tsukuda Takuo

  公开号：US20090247524A1

  公开（公告）日：2009-10-01

  Compounds represented by formula (1) shown below, pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising such compounds are provided.

  提供了由下式（1）表示的化合物、药学上可接受的盐以及包含这些化合物的制药组合物。
• US8193351B2
  申请人：——

  公开号：US8193351B2

  公开（公告）日：2012-06-05
• HSP90 INHIBITOR
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP2036895B1

  公开（公告）日：2013-01-16
• Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazines as novel Hsp90 inhibitors
  作者：Atsushi Suda、Ken-ichi Kawasaki、Susumu Komiyama、Yoshiaki Isshiki、Dong-Oh Yoon、Sung-Jin Kim、Young-Jun Na、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.bmc.2013.11.036

  日期：2014.1

  A novel series of 2-amino-1,3,5-triazines bearing a tricyclic moiety as heat shock protein 90 (Hsp90) inhibitors is described. Molecular design was performed using X-ray cocrystal structures of the lead compound CH5015765 and natural Hsp90 inhibitor geldanamycin with Hsp90. We optimized affinity to Hsp90, in vitro cell growth inhibitory activity, water solubility, and liver microsomal stability of inhibitors and identified CH5138303. This compound showed high binding affinity for N-terminal Hsp90 alpha (K-d = 0.52 nM) and strong in vitro cell growth inhibition against human cancer cell lines (HCT116 IC50 = 0.098 mu M, NCI-N87 IC50 = 0.066 mu M) and also displayed high oral bioavailability in mice (F = 44.0%) and potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model (tumor growth inhibition = 136%). (C) 2013 Elsevier Ltd. All rights reserved.