1-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-imidazol-1-ylmethylphenyl)-1H-[1,2,3]triazole-4-carboxylic acid ethylamide | 1383717-45-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-imidazol-1-ylmethylphenyl)-1H-[1,2,3]triazole-4-carboxylic acid ethylamide
• 英文别名: SST0441AA1；1-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-5-[4-(imidazol-1-ylmethyl)phenyl]triazole-4-carboxamide
• CAS: 1383717-45-0
• 化学式: C₂₄H₂₆N₆O₃
• 分子量: 446.509
• InChiKey: ZSOQWPOVGAAMDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-(4-methanesulfonyloxy-methyl-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid methyl ester 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 52.0h， 生成 1-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-imidazol-1-ylmethylphenyl)-1H-[1,2,3]triazole-4-carboxylic acid ethylamide
  参考文献：
  名称：

  Synthesis and Evaluation of New Hsp90 Inhibitors Based on a 1,4,5-Trisubstituted 1,2,3-Triazole Scaffold

  摘要：

  Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates gave a new family of 1,4,5-trisubstituted triazole carboxylic acid derivatives that showed high affinity toward Hsp90 associated with cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in position 4 of the triazole ring were essential to get high activity. Docking simulations suggested that the triazoles penetrate the Hsp90 ATP binding site. Some 1,4,5-trisubstituted triazole carboxamides induced dramatic depletion of the examined client proteins and a very strong increase in the expression levels of the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922. One of them, (compound 18, SST0287CL1) was selected for further investigation as the most promising drug candidate.

  DOI：

  10.1021/jm401536b

文献信息

• [EN] ARYL TRIAZOLE COMPOUNDS WITH ANTITUMOURAL ACTIVITY<br/>[FR] COMPOSÉS ARYL TRIAZOLE AYANT UNE ACTIVITÉ ANTI-TUMORALE
  申请人：SIGMA TAU RES SWITZERLAND SA

  公开号：WO2012084602A1

  公开（公告）日：2012-06-28

  The present invention relates to aryl triazole derivatives of Formula I having antitumoural activity through, as one possible biological target, the molecular chaperone heat shock protein 90 (Hsp90) inhibition. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of Hsp90 is responsive, and the pharmaceutical composition containing such compounds.

  本发明涉及具有抗肿瘤活性的Formula I的芳基三唑衍生物，作为一个可能的生物靶标，通过分子伴侣热休克蛋白90（Hsp90）的抑制作用。该发明包括在医学上使用这些化合物，涉及癌症疾病以及其他需要抑制Hsp90的疾病，以及含有这些化合物的药物组合物。
• ARYL TRIAZOLE COMPOUNDS WITH ANTITUMOURAL ACTIVITY
  申请人：Giannini Giuseppe

  公开号：US20140329812A1

  公开（公告）日：2014-11-06

  The present invention relates to aryl triazole derivatives of Formula I having antitumoural activity through, as one possible biological target, the molecular chaperone heat shock protein 90 (Hsp90) inhibition. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of Hsp90 is responsive, and the pharmaceutical composition containing such compounds.

  本发明涉及公式I的芳基三唑衍生物，通过作为可能的生物靶点之一，分子伴侣热休克蛋白90（Hsp90）抑制具有抗肿瘤活性。本发明包括将这些化合物用于医学，与癌症疾病以及其他需要抑制Hsp90的疾病有关，并且包含这些化合物的制药组合物。
• Exploring in vitro and in vivo Hsp90 inhibitors activity against human protozoan parasites
  作者：Giuseppe Giannini、Gianfranco Battistuzzi

  DOI：10.1016/j.bmcl.2014.12.048

  日期：2015.2

  A set of compounds, previously selected as potent Hsp90 alpha inhibitors, has been studied on a panel of human parasites. 5-Aryl-3,4-isoxazolediamide derivatives (1) were active against two protozoa, Trypanosoma brucei rhodesiense and Plasmodium falciparum, with a good tolerability toward cytotoxicity on non-malignant L6 rat myoblast cell line, unlike the 1,5-diaryl,4-carboxamides-1,2,3-triazole derivatives (2) which, while showing a single-digit nM range activity against the same protozoa, were also highly cytotoxic on L6 cells. In a subsequent in vivo study, two isoxazolediamide derivatives, 1a and 1b, were very efficacious on the sleeping sickness-causing agent with a clear parasitaemia during treatment. These data, however, showed that not all protozoa are sensitive to Hsp90 inhibitors, as well as not all Hsp90 inhibitors are equally active on parasites. (C) 2014 Elsevier Ltd. All rights reserved.
• [EN] TARGETED THERAPEUTICS<br/>[FR] AGENTS THÉRAPEUTIQUES CIBLES
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2015143004A9

  公开（公告）日：2016-09-29
• TARGETED THERAPEUTICS
  申请人：Synta Pharmaceuticals Corp.

  公开号：EP3131586A1

  公开（公告）日：2017-02-22