5-[2,4-bis(benzyloxy)-5-chlorophenyl]isoxazole-3-carboxylic acid | 1202921-29-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[2,4-bis(benzyloxy)-5-chlorophenyl]isoxazole-3-carboxylic acid
• 英文别名: 5-[2,4-bis(benzyloxy)-5-chlorophenyl]-isoxazole-3-carboxylic acid；5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1,2-oxazole-3-carboxylic acid
• CAS: 1202921-29-6
• 化学式: C₂₄H₁₈ClNO₅
• 分子量: 435.864
• InChiKey: IRUQDZYRLKBZPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  81.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-[2,4-bis(benzyloxy)-5-chlorophenyl]isoxazole-3-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 5-[2,4-bis(benzyloxy)-5-chlorophenyl]-N-(2,2,2-trifluoroethyl)isoxazole-3-carboxamide
  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
• 作为产物：
  描述：

  ethyl 5-[2,4-bis(benzyloxy)-5-chlorophenyl]isoxazole-3-carboxylate 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 生成 5-[2,4-bis(benzyloxy)-5-chlorophenyl]isoxazole-3-carboxylic acid
  参考文献：
  名称：

  [EN] 5-PHENYL-ISOXAZOLE-3-CARBOXAMIDES MODULATING HSP90 WITH ANTITUMORAL ACTIVITIES
  [FR] 5-PHÉNYL-ISOXAZOLE-3-CARBOXAMIDES MODULANT HSP90 AYANT DES ACTIVITÉS ANTITUMORALES

  摘要：

  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。

  公开号：

  WO2010000748A1

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。
• Aryl isoxazole compounds with antitumoural activities
  申请人：Giannini Giuseppe

  公开号：US08383616B2

  公开（公告）日：2013-02-26

  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，通过作为一种可能的生物靶点，抑制分子伴侣热休克蛋白90（Hsp90）。本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，并包含含有这些化合物的药物组合物。
• 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