ST0201CL1 | 1202967-76-7

• 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: ST0201CL1
• 英文别名: 5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylbenzoylamino)isoxazole-3-carboxylic acid ethylamide；5-(2,4-dihydroxy-5-isopropyl-phenyl)-N-ethyl-4-[[4-(morpholinomethyl)benzoyl]amino]isoxazole-3-carboxamide；5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[[4-(morpholin-4-ylmethyl)benzoyl]amino]-1,2-oxazole-3-carboxamide
• CAS: 1202967-76-7
• 化学式: C₂₇H₃₂N₄O₆
• 分子量: 508.574
• InChiKey: QJYYBJJIRLBFHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-[2,4-bis(benzyloxy)-5-isopropylphenyl]-4-nitroisoxazole-3-carboxylic acid ethylamide 在 水 、 三氯化硼 、 氯化铵 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.92h， 生成 ST0201CL1
  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

• TARGETED THERAPEUTICS
  申请人：Chimmanamada Dinesh U.

  公开号：US20140079636A1

  公开（公告）日：2014-03-20

  The present invention provides pharmacological compounds including an effector moiety conjugated to an binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供了药理化合物，包括将效应器基团偶联到结合基团上，以将效应器基团定向到感兴趣的生物靶点。同样，本发明提供了包括该化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。该化合物可以被描述为蛋白质相互作用的结合基团-药物偶联物（SDC-TRAP）化合物，包括蛋白质相互作用的结合基团和效应器基团。例如，在治疗癌症的某些实施方案中，SDC-TRAP可以包括Hsp90抑制剂与细胞毒素剂作为效应器基团的偶联物。
• Methods of treating a metabolic syndrome by modulating heat shock protein (HSP) 90-beta
  申请人：Berg LLC

  公开号：US10023864B2

  公开（公告）日：2018-07-17

  The invention provides HSP90β inhibitors comprising an antisense oligonucleotide targeting HSP90β, pharmaceutical compositions comprising said inhibitors and methods of treatment of a metabolic syndrome by administering said HSP90β inhibitors to a subject in need thereof. The antisense oligonucleotides may be targeted to skeletal muscle.

  本发明提供了由靶向 HSP90β 的反义寡核苷酸组成的 HSP90β 抑制剂、由所述抑制剂组成的药物组合物以及通过向有需要的受试者施用所述 HSP90β 抑制剂来治疗代谢综合征的方法。反义寡核苷酸可靶向骨骼肌。
• Targeted therapeutics
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：US10232049B2

  公开（公告）日：2019-03-19

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供的药理化合物包括与结合基团共轭的效应分子，该结合基团可将效应分子导向感兴趣的生物靶标。同样，本发明还提供了包括这些化合物的组合物、试剂盒和方法（如治疗、诊断和成像）。这些化合物可被描述为蛋白质相互作用结合分子-药物共轭物（SDC-TRAP）化合物，其中包括蛋白质相互作用结合分子和效应分子。例如，在某些用于治疗癌症的实施方案中，SDC-TRAP 可包括与细胞毒剂共轭的 Hsp90 抑制剂作为效应分子。
• Combination therapies comprising targeted therapeutics
  申请人：MADRIGAL PHARMACEUTICALS, INC.

  公开号：US11491145B2

  公开（公告）日：2022-11-08

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供的药理化合物包括与结合基团共轭的效应分子，该结合基团可将效应分子导向感兴趣的生物靶标。同样，本发明还提供了包括这些化合物的组合物、试剂盒和方法（如治疗、诊断和成像）。这些化合物可被描述为蛋白质相互作用结合分子-药物共轭物（SDC-TRAP）化合物，其中包括蛋白质相互作用结合分子和效应分子。例如，在某些用于治疗癌症的实施方案中，SDC-TRAP 可包括与细胞毒剂共轭的 Hsp90 抑制剂作为效应分子。
• 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.