| 1350723-08-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• CAS: 1350723-08-8
• 化学式: C₉H₁₁ClN₂O₃
• 分子量: 230.651
• InChiKey: PHJOFCBESMTUAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.89
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.57
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-amino-5-[2,4-bis(benzyloxy)-5-isopropylphenyl]isoxazole-3-carboxylic acid ethylamide 、 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 C₃₈H₄₁N₅O₇
  参考文献：
  名称：

  Novel 3,4-Isoxazolediamides as Potent Inhibitors of Chaperone Heat Shock Protein 90

  摘要：

  A structural investigation on the isoxazole scaffold led to the discovery of 3,4-isoxazolediamide compounds endowed with potent Hsp90 inhibitory properties. We have found that compounds possessing a nitrogen atom directly attached to the C-4 heterocycle ring possess in vitro Hsp90 inhibitory properties at least comparable to those of the structurally related 4,S-diarylisoxazole derivatives. A group of compounds from this series of diamides combine potent binding affinity and cell growth inhibitory activity in both series of alkyl- and aryl- or heteroarylarnides, with IC50 in the low nanomolar range. The 3,4-isoxazolediamides were also very effective in causing dramatic depletion of the examined client proteins and, as expected for the Hsp90 inhibitors, always induced a very strong increase in the expression levels of the chaperone Hsp70. In vivo studies against human epidermoid carcinoma A431 showed an antitumor effect of morpholine derivative 73 comparable to that induced by the reference compound 10.

  DOI：

  10.1021/jm201155e

文献信息

• 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.