2-((2-aminoethyl)dithio)-1-ethanol | 15579-01-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 有机二硫化物
• 英文名称: 2-((2-aminoethyl)dithio)-1-ethanol
• 英文别名: 2-[(2-aminoethyl)disulfanyl]ethan-1-ol；2-(2-aminoethyldisulfanyl)ethanol；2-aminoethyl-2-hydroxyethyl disulfide；Aminoethyl-SS-ethylalcohol
• CAS: 15579-01-8
• 化学式: C₄H₁₁NOS₂
• 分子量: 153.269
• InChiKey: OAHFAPXIBISUJB-UHFFFAOYSA-N

物化性质

• 沸点：
  284.1±25.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  8
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  96.8
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

生物活性

Aminoethyl-SS-ethylalcohol 是一种谷胱甘肽可降解的 ADC 链接剂，可用于合成抗体偶联药物（ADC）。

靶点

	Cleavable

体外研究

ADCs 由连接有 ADC 细胞毒物的抗体构成。

反应信息

• 作为反应物：
  描述：

  N-甲氧基羰基顺丁烯二酰亚胺 、 2-((2-aminoethyl)dithio)-1-ethanol 在 碳酸氢钠 作用下， 以 水 为溶剂， 反应 0.83h， 生成 1-{2-[(2-hydroxyethyl)disulfanyl]ethyl}-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  在定制控制释放的碳酸盐/氨基甲酸酯键与还原键敏感的二硫键连接基团之间寻求平衡：原位共价结合白蛋白的吉西他滨前药可促进生物利用度和肿瘤蓄积。

  摘要：

  为了解决快速酶灭活，不良肿瘤靶向以及吉西他滨（GEM）应用中获得的耐药性的挑战，我们报道了两组由马来酰亚胺官能化的GEM前药与血液循环白蛋白的Cys-34共价共价结合，然后产生静脉给药后在大分子前药中的作用。通过链接键的不同组合（相对稳定和不稳定（分别为氨基甲酸酯和碳酸酯）以及带有或不带有二硫键的连接子）可以实现量身定制的精确控制释放。有趣的是，我们发现二硫键带来的总体优缺点随着连接键的稳定性而变化。最后，带有碳酸酯键的基团，尤其是带有缺乏二硫键的连接基的基团，体内抗肿瘤功效。

  DOI：

  10.1021/acs.jmedchem.8b00293
• 作为产物：
  描述：

  巯基乙胺 、 2-巯基乙醇 在 碘 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以37.2%的产率得到2-((2-aminoethyl)dithio)-1-ethanol
  参考文献：
  名称：

  基于GSH响应的诊治一体化有机分子探针及其制备方法

  摘要：

  本发明公开了一种基于GSH响应的诊治一体化有机分子探针及其制备方法，构建一类基于近红外荧光染料和肿瘤微环境的诊治一体化的分子影像探针，GSH可通过氧化还原作用切断该探针中的二硫键，释放出活性药物，达到监测药物的传输与释放的目的。本发明合成过程相对简单快速，活性药物释放快速，作用周期短，对正常细胞副作用小，具有巨大的应用潜力，反应步骤简单、操作流程清晰，并且将分子影像探针与抗癌前药相结合，通过设计合理的结构，既可实现对肿瘤的靶向检测，也能实现靶向治疗肿瘤的效果，同时能监测前药在生物体内的生物分布，以及活性药物的释放及富集过程，对研究药物的作用机制、肿瘤的抗药性机理等具有重大意义。

  公开号：

  CN106188191A

文献信息

• Prodrugs containing novel bio-cleavable linkers
  申请人：Satyam Apparao

  公开号：US20060046967A1

  公开（公告）日：2006-03-02

  The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula I.

  本发明提供了公式(I)的化合物或其药用可接受的盐。本发明还提供了包含一个或多个公式I的化合物或其中间体以及一个或多个药用可接受的载体、车辆或稀释剂的药物组合物。本发明进一步提供了包括制备方法和使用方法在内的前药，包括释放一氧化氮的前药、双前药和相互前药，由公式I的化合物组成。
• [EN] CAMPTOTHECIN DERIVATIVES WITH A DISULFIDE MOIETY AND A PIPERAZINE MOIETY<br/>[FR] DÉRIVÉS DE CAMPTOTHÉCINE AYANT UNE FRACTION DISULFURE ET UNE FRACTION PIPÉRAZINE
  申请人：SUN PHARMA ADVANCED RES CO LTD

  公开号：WO2021005583A1

  公开（公告）日：2021-01-14

  This invention provides a compound of Formula I or a pharmaceutically acceptable salt thereof (wherein X, Y, Z and n are defined herein). These compounds are useful in the treatment of diseases mediated by topoisomerase I enzyme such as cancers. The present invention also provides processes for the preparation of compounds of Formula I. The compounds of the present invention are more water soluble, stable in buffer solution at various pH, and exhibit better anti-tumor activity and rapid release of SN-38 in tumor microenvironments.

  这项发明提供了一种式I化合物或其药用可接受盐（其中X、Y、Z和n在此处定义）。这些化合物在治疗由拓扑异构酶I介导的疾病，如癌症方面具有用处。本发明还提供了制备式I化合物的方法。本发明的化合物在水溶液中更稳定，在各种pH缓冲溶液中更稳定，并且在肿瘤微环境中表现出更好的抗肿瘤活性和SN-38的快速释放。
• NO-NSAIDs: Gastric-sparing nitric oxide-releasable prodrugs of non-steroidal anti-inflammatory drugs
  作者：Kumar V.S. Nemmani、Sunil V. Mali、Namdev Borhade、Asif R. Pathan、Manoj Karwa、Venu Pamidiboina、S.P. Senthilkumar、Machhindra Gund、Arun K. Jain、Naveen K. Mangu、Nauzer P. Dubash、Dattatraya C. Desai、Somesh Sharma、Apparao Satyam

  DOI：10.1016/j.bmcl.2009.07.142

  日期：2009.9

  Recently, a new class of nitric-oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) is being studied as 'Safe NSAIDs' because of their gastric-sparing properties. As an extension of our novel disulfide linker technology, we have designed, synthesized and evaluated novel NO-releasing NSAID prodrugs such as NO-Aspirin (1b-d) and NO-Diclofenac (2b-c). Although the amide-containing derivative 1d did not show any bioavailability, the remaining compounds have shown fair to excellent pharmacokinetic. anti-inflammatory and gastric-sparing properties. Among them, however, the NO-Diclofenac (2b) has shown the most promising pharmacokinetic, anti-inflammatory and NO-releasing properties and protected rats from NSAID-induced gastric damage which could be attributable to the beneficial effects of NO released from these prodrugs. (C) 2009 Elsevier Ltd. All rights reserved.
• 5-(2-Aminoethyl)dithio-2-nitrobenzoate as a More Base-Stable Alternative to Ellman's Reagent
  作者：Jinge Zhu、Ilirian Dhimitruka、Dehua Pei

  DOI：10.1021/ol048404+

  日期：2004.10.1

  (GRAPHICS)5-(2-Aminoethyl)dithio-2-nitrobenzoate (ADNB) reacts with free thiols with kinetics similar to those of Ellman's reagent but has dramatically improved stability under alkaline conditions, making it an excellent alternative to Ellman's reagent for the quantitation of thiol contents and enzymatic assays under basic pH conditions.
• A Kinetic Approach to Characterize the Electrostatic Environments of Thiol Groups in Proteins
  作者：Hao Zhang、Min Le、Gary E. Means

  DOI：10.1006/bioo.1998.1112

  日期：1998.12

  In this study, we synthesized a zwitterionic DTNB derivative, 5-(2-aminoethyl)-dithio-2-nitrobenzoate (ADNB), and characterized its reactions with several cationic, anionic, and neutral thiols. Reactions with ADNB, unlike those with DTNB, are relatively insensitive to electrostatic environments and ionic strengths. At relatively low ionic strength, rate ratios, k(ADNB)/k(DTNB), varied from 0.22 for reactions with low-molecular-weight cationic thiols to 3.0 for those with low-molecular-weight anionic thiols. A k(ADNB)/k(DTNB) ratio of similar to 200 for Cys-34 of BSA appears to reflect a very anionic environment. k(ADNB)/k(DTNB) ratios of similar to 6 and similar to 1, respectively, for canine and equine serum albumins, which have Glu-82 -->, Asp and Glu-82 -->, Ala substitutions suggest Glu-82 is the most important anionic residues affecting the reactivity of Cys-34 in BSA. k(ADNB)/k(DTNB) ratios appear to be useful for characterizing electrostatic environments of thiol groups in proteins. (C) 1998 Academic Press.