2,4-二羟基-5-异丙基苯并二硫酸 | 1046490-81-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2,4-二羟基-5-异丙基苯并二硫酸
• 英文名称: 2,4-dihydroxy-5-isopropylbenzodithioic acid
• 英文别名: 2,4-dihydroxy-5-isopropylbenzenecarbodithioic acid；2,4-dihydroxy-5-propan-2-ylbenzenecarbodithioic acid
• CAS: 1046490-81-6
• 化学式: C₁₀H₁₂O₂S₂
• 分子量: 228.336
• InChiKey: HWRNABBONOFDIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  73.6
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险类别：
  6.1
• 危险性防范说明：
  P501,P261,P270,P271,P264,P280,P337+P313,P305+P351+P338,P361+P364,P332+P313,P301+P310+P330,P302+P352+P312,P304+P340+P311,P403+P233,P405
• 危险品运输编号：
  2811
• 危险性描述：
  H301+H311+H331,H315,H319
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  2,4-二羟基-5-异丙基苯并二硫酸 在 碳酸氢钠 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 methyl 1-(4-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-hydroxy-4H-1,2,4-triazol-4-yl)benzyl)piperidine-4-carboxylate
  参考文献：
  名称：

  METHODS AND COMPOSITIONS FOR MODULATING KRAS(G12D)

  摘要：

  Provided are tumor- targeted protein degradation chimeras, termed chaperone- mediated protein degraders (CHAMPs) comprising a first moiety that is capable of binding to a target protein (e.g., KRAS(G12D) or proteins and a second moiety that is capable of binding a chaperone protein or proteins or protein component of chaperone complexes (e.g., HSP90). Pharmacetuical compositions comprising the disclosed CHAMPs and their uses for treating thereof, which are useful for treating cancers and related conditions are also provided.

  公开号：

  WO2024044334A2
• 作为产物：
  描述：

  1-(2,4-双(苄氧基)苯基)乙酮 在 正丁基锂 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.5h， 生成 2,4-二羟基-5-异丙基苯并二硫酸
  参考文献：
  名称：

  Radiosynthesis, biological evaluation and preliminary microPET study of 18F-labeled 5-resorcinolic triazolone derivative based on ganetespib targeting HSP90

  摘要：

  Heat-shock protein 90 (HSP90) is a molecular chaperone that activates oncogenic transformation in several solid tumors, including lung and breast cancers. Ganetespib, a most promising candidate among several HSP90 inhibitors under clinical trials, has entered Phase III clinical trials for cancer therapy. Despite numerous evidences validating HSP90 as a target of anticancer, there are few studies on PET agents targeting oncogenic HSP90. In this study, we synthesized and biologically evaluated a novel F-18-labeled 5-resorcinolic triazolone derivative (1, [F-18]PTP-Ganetespib) based on ganetespib. [F-18]PTP-Ganetespib was labeled by click chemistry of Ganetespib-PEG-Alkyne (10) and [F-18]PEG-N-3 (11) with 37.3 +/- 5.11% of radiochemical yield and 99.7 +/- 0.09% of radiochemical purity. [F-18]PTP-Ganetespib showed proper LogP (0.96 +/- 0.06) and good stability in human serum over 97% for 2 h. [F-18]PTP-Ganetespib showed high uptakes in breast cancer cells containing triple negative breast cancer (TNBC) MDA-MB-231 and Her2-negative MCF-7 cells, which are target breast cancer cell lines of HSP90 inhibitor, ganetespib, as an anticancer. Blocking of HSP90 by the pretreatment of ganetespib exhibited significantly decreased accumulation of [F-18]PTP-Ganetespib in MDA-MB-231 and MCF-7 cells, indicating the specific binding of [F-18]PTP-Ganetespib to MDA-MB-231 and MCF-7 cells with high HSP90 expression. In the biodistribution and microPET imaging studies, the initial uptake into tumor was weaker than in other thoracic and abdominal organs, but [F-18]PTP-Ganetespib was retained relatively longer in the tumor than other organs. The uptake of [F-18]PTP-Ganetespib in tumors was not sufficient for further development as a tumor-specific PET imaging agent by itself, but this preliminary PET imaging study of [F-18]PTP-Ganetespib can be basis for developing new PET imaging agents based on HSP90 inhibitor, ganetespib.

  DOI：

  10.1016/j.bmcl.2018.10.035
• 作为试剂：
  描述：

  2,4-二羟基-5-异丙基苯并二硫酸 、 tert-butyl 4-(2-(5-amino-1H-indol-1-yl)ethyl)piperidine-1-carboxylate 在 2,4-二羟基-5-异丙基苯并二硫酸 作用下， 生成 tert-butyl 4-(2-(5-(2,4-dihydroxy-5-isopropylphenylthioamido)-1H-indol-1-yl)ethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  TARGETED THERAPEUTICS

  摘要：

  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。

  公开号：

  US20140079636A1

文献信息

• 3,4-二苯基-4H-1,2,4-三唑衍生物及其制备 方法和应用
  申请人：上海翰森生物医药科技有限公司

  公开号：CN106349233B

  公开（公告）日：2021-06-01

  本发明公开了3,4‑二苯基‑4H‑1,2,4‑三唑衍生物及其制备方法和应用。具体地，本发明涉及具有式(I)结构的3,4‑二苯基‑4H‑1,2,4‑三唑衍生物、其立体异构体或其药学上可接受盐，其中式(I)中各取代基的定义与说明书中的定义相同。这些结构新颖的化合物具有热休克蛋白HSP90抑制活性，可用于治疗癌症、神经退行性疾病、炎症性疾病、自身免疫性疾病、缺血性脑损伤等用途，具有广阔的应用前景。
• [EN] TARGETED THERAPEUTICS<br/>[FR] THÉRAPEUTIQUE CIBLÉE
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2015038649A1

  公开（公告）日：2015-03-19

  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.

  本发明提供了包括与将效应子导向至感兴趣的生物靶点的结合基团共轭的药理化合物。同样，本发明提供了包括这些化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。这些化合物可以被描述为蛋白质相互作用结合基团-药物共轭（SDC-TRAP）化合物，其中包括蛋白质相互作用结合基团和效应子。例如，在针对治疗癌症的某些实施方式中，SDC-TRAP可以包括Hsp90抑制剂共轭到细胞毒性药剂作为效应子。
• [EN] HSP90-TARGETING CONJUGATES AND FORMULATIONS THEREOF<br/>[FR] CONJUGUÉS CIBLANT HSP90 ET FORMULATIONS DE CES DERNIERS
  申请人：TARVEDA THERAPEUTICS INC

  公开号：WO2018112176A1

  公开（公告）日：2018-06-21

  Conjugates of an active agent attached to a targeting moiety, such as an HSP90 binding moiety, via a linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.

  已设计出将活性剂与靶向基团（例如HSP90结合基团）通过连接剂连接在一起的共轭物，以及包含这种共轭物的粒子。这种共轭物和粒子可以提供改善活性剂的时间空间传递、改善在肿瘤中的生物分布和穿透性，以及/或减少毒性。提供了制备这些共轭物、粒子和其配方的方法。提供了将这些配方用于治疗或预防癌症等需要的受试者的方法。
• [EN] METHODS AND COMPOSITIONS FOR TARGETED PROTEIN DEGRADATION<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR UNE DÉGRADATION DE PROTÉINE CIBLÉE
  申请人：RANOK THERAPEUTICS HANGZHOU CO LTD

  公开号：WO2020207396A1

  公开（公告）日：2020-10-15

  Provided herein are methods and compositions for targeted protein degradation. In one aspect, a protein degradation chimera is provided, comprising: a first moiety that is capable of binding to a chaperone complex component; a second moiety that is capable of binding to a target protein or proteins, wherein the target protein (s) is targeted for degradation; and a tether configured to covalently couple the first moiety and the second moiety.

  本文提供了用于靶向蛋白质降解的方法和组合物。在一个方面，提供了一种蛋白质降解嵌合体，包括：能够结合到辅助蛋白复合物成分的第一部分；能够结合到目标蛋白质的第二部分，其中目标蛋白质被靶向降解；以及用于共价耦合第一部分和第二部分的连接物。
• [EN] NOVEL TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY<br/>[FR] NOUVEAUX COMPOSÉS TRIAZOLES QUI MODULENT L'ACTIVITÉ HSP90
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2013152206A1

  公开（公告）日：2013-10-10

  The present invention relates to novel triazole Hsp90 inhibitors that possess significant inhibitory activity against Hsp90, which are suitable for the treatment of hyperproliferative diseases such as cancer, infections, immune disorders, inflammation, and CNS related disorders. Furthermore, pharmaceutical compositions, including combination products, are also provided in the present application. Further provided are methods of using the pharmaceutical compositions and/or combination products.

  本发明涉及新型三唑Hsp90抑制剂，具有显著的对Hsp90的抑制活性，适用于治疗癌症、感染、免疫紊乱、炎症和中枢神经系统相关疾病等高增殖性疾病。此外，本申请还提供了包括联合产品在内的药物组合物。还提供了使用药物组合物和/或联合产品的方法。