4-amino-5-[2,4-bis(benzyloxy)-5-isopropylphenyl]isoxazole-3-carboxylic acid ethylamide | 1202920-72-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-amino-5-[2,4-bis(benzyloxy)-5-isopropylphenyl]isoxazole-3-carboxylic acid ethylamide
• 英文别名: 4-amino-5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-N-ethyl-1,2-oxazole-3-carboxamide
• CAS: 1202920-72-6
• 化学式: C₂₉H₃₁N₃O₄
• 分子量: 485.583
• InChiKey: ADQACDHOUOIMAK-UHFFFAOYSA-N

物化性质

• 沸点：
  665.0±55.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  99.6
• 氢给体数：
  2
• 氢受体数：
  6

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 三氯化硼 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 31.33h， 生成 1-[6-({5-(2,4-dihydroxy-5-isopropylphenyl)-3-[(ethylamino)carbonyl]isoxazol-4-yl}amino)-6-oxohexyl]pyridinium bromide
  参考文献：
  名称：

  具有阳离子成分的新型TRAP1和Hsp90分子伴侣抑制剂：线粒体靶向的初步研究。

  摘要：

  TRAP1（Hsp75）是Hsp90分子伴侣家族的线粒体旁系同源物。由于Hsp90分子伴侣之间的结构相似性，已设想了一种潜在的通过线粒体TRAP1 ATPase抑制作用诱导凋亡的策略，并且通过将已知Hsp90抑制剂的简单药效学核心与带有永久阳离子头的各种附件结合，开发了一系列化合物在生理pH下高度可离子化的碱性基团。选择阳离子附件作为将药物递送至线粒体的媒介。实际上，已证明大量新衍生物积聚在结肠癌细胞的线粒体级分中，以及一系列带有胍类附属物的化合物，

  DOI：

  10.1016/j.bmcl.2018.05.031
• 作为产物：
  描述：

  5-[2,4-bis(benzyloxy)-5-isopropylphenyl]-4-nitroisoxazole-3-carboxylic acid ethylamide 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 4-amino-5-[2,4-bis(benzyloxy)-5-isopropylphenyl]isoxazole-3-carboxylic acid ethylamide
  参考文献：
  名称：

  Exploring in vitro and in vivo Hsp90 inhibitors activity against human protozoan parasites

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2014.12.048

文献信息

• [EN] 5-PHENYL-ISOXAZOLE-3-CARBOXAMIDES MODULATING HSP90 WITH ANTITUMORAL ACTIVITIES<br/>[FR] 5-PHÉNYL-ISOXAZOLE-3-CARBOXAMIDES MODULANT HSP90 AYANT DES ACTIVITÉS ANTITUMORALES
  申请人：SIGMA TAU RES SWITZERLAND SA

  公开号：WO2010000748A1

  公开（公告）日：2010-01-07

  The present invention relates to formula I compounds having antitumoural activities 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 compositions containing such compounds.

  本发明涉及具有抗肿瘤活性的I类化合物，其中作为一种可能的生物靶点，通过分子伴侣热休克蛋白90（Hsp90）的抑制来发挥作用。该发明涵盖了在医学上使用这些化合物，涉及癌症疾病以及其他需要Hsp90抑制的疾病，并含有这些化合物的药物组合物。
• ARYL ISOXAZOLE COMPOUNDS WITH ANTITUMOURAL ACTIVITIES
  申请人：Giannini Giuseppe

  公开号：US20110245221A1

  公开（公告）日：2011-10-06

  The present invention relates to formula I compounds having antitumoural activities 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 compositions containing such compounds.

  本发明涉及具有抗肿瘤活性的I式化合物，其中一种可能的生物靶点是分子伴侣热休克蛋白90（Hsp90）的抑制作用。本发明包括在医学上使用这些化合物，与癌症疾病以及其他需要抑制Hsp90的疾病有关，并且包括含有这些化合物的制药组合物。
• Novel 3,4-Isoxazolediamides as Potent Inhibitors of Chaperone Heat Shock Protein 90
  作者：Riccardo Baruchello、Daniele Simoni、Giuseppina Grisolia、Giuseppina Barbato、Paolo Marchetti、Riccardo Rondanin、Stefania Mangiola、Giuseppe Giannini、Tiziana Brunetti、Domenico Alloatti、Grazia Gallo、Andrea Ciacci、Loredana Vesci、Massimo Castorina、Ferdinando M. Milazzo、Maria L. Cervoni、Mario B. Guglielmi、Marcella Barbarino、Rosanna Foderà、Claudio Pisano、Walter Cabri

  DOI：10.1021/jm201155e

  日期：2011.12.22

  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.
• 5-PHENYL-ISOXAZOLE-3-CARBOXAMIDES MODULATING HSP90 WITH ANTITUMORAL ACTIVITIES
  申请人：SIGMA-TAU Research Switzerland S.A.

  公开号：EP2310377A1

  公开（公告）日：2011-04-20
• US8383616B2
  申请人：——

  公开号：US8383616B2

  公开（公告）日：2013-02-26