2-(2-(methacryloyloxy)ethylthio)acetic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-(2-(methacryloyloxy)ethylthio)acetic acid
• 英文别名: 2-[(carboxymethyl)thio]ethyl 2-methyl-2-propenoate；2-[2-(2-methylprop-2-enoyloxy)ethylsulfanyl]acetic acid
• 化学式: C₈H₁₂O₄S
• 分子量: 204.247
• InChiKey: BAPREXHHSGFCPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-(methacryloyloxy)ethylthio)acetic acid 在 sodium periodate 作用下， 以 水 、 乙腈 为溶剂， 以81%的产率得到2-(2-(methacryloyloxy)ethylsulfinyl)acetic acid
  参考文献：
  名称：

  具有可定制释放动力学的糖皮质激素负载核心交联聚合物胶束用于类风湿性关节炎的靶向治疗

  摘要：

  可聚合和可水解裂解的地塞米松（DEX，图中红点）衍生物共价包裹在由热敏嵌段共聚物（黄色和灰色结构单元）制备的核心交联聚合物胶束中。通过改变药物接头中硫醚的氧化程度，可以控制 DEX 的释放速率。在两种动物模型中，加载 DEX 的胶束用于有效治疗炎症性关节炎。

  DOI：

  10.1002/anie.201202713
• 作为产物：
  描述：

  2-(2-tert-butoxy-2-oxoethylthio)ethyl methacrylate 在 4-甲氧基苯酚 、 三氟乙酸 作用下， 反应 2.0h， 以63%的产率得到2-(2-(methacryloyloxy)ethylthio)acetic acid
  参考文献：
  名称：

  具有可定制释放动力学的糖皮质激素负载核心交联聚合物胶束用于类风湿性关节炎的靶向治疗

  摘要：

  可聚合和可水解裂解的地塞米松（DEX，图中红点）衍生物共价包裹在由热敏嵌段共聚物（黄色和灰色结构单元）制备的核心交联聚合物胶束中。通过改变药物接头中硫醚的氧化程度，可以控制 DEX 的释放速率。在两种动物模型中，加载 DEX 的胶束用于有效治疗炎症性关节炎。

  DOI：

  10.1002/anie.201202713

文献信息

• [EN] CONTROLLED RELEASE SYSTEM<br/>[FR] SYSTÈME DE LIBÉRATION CONTRÔLÉE
  申请人：CRISTAL DELIVERY B V

  公开号：WO2013002636A1

  公开（公告）日：2013-01-03

  The present invention relates to controlled release systems that may be administered other than intravenously. The controlled release system is directed to active ingredients, entrapped in or otherwise incorporated in or coupled to polymer carriers or polymeric devices, such as micelles, nanoparticles, microspheres and other types of polymer devices for controlled release; the active ingredients are covalently bonded to the polymer carriers or polymeric devices. The controlled release systems may suitably be used to treat diseases.

  本发明涉及除静脉注射外的可控释放系统。该可控释放系统针对活性成分，这些活性成分被包裹在或以其他方式纳入聚合物载体或聚合物设备中，例如胶束、纳米颗粒、微球和其他类型的聚合物设备，以进行可控释放；这些活性成分与聚合物载体或聚合物设备共价结合。该可控释放系统可适用于治疗疾病。
• TUNABLE, BIODEGRADABLE LINKER MOLECULES FOR TRANSIENT CONJUGATION OF COMPONENTS IN DRUG DELIVERY SYSTEMS, AND DRUG DELIVERY SYSTEMS PREPARED THEREWITH
  申请人：Rijcken Cristianne Johanna Ferdinand

  公开号：US20130261094A1

  公开（公告）日：2013-10-03

  The present invention relates to a particular class of biodegradable linkers, ensuring transiently stable conjugation of building blocks and/or bioactive compounds into drug delivery systems (DDS), such as DDS based on polymeric micelles or hydrogels. In addition, the present invention relates to compounds, comprising said linkers, such compounds preferably being prodrugs. Further, the invention is directed to the use of said linkers, and especially said biodegradable linkers, in a drug delivery system. Moreover, the invention relates to controlled release system comprising a polymer matrix, capable of releasing an active ingredient, wherein the active ingredient is covalently linked to the polymer molecules of the polymer matrix through said linkers, as well as to a method of synthesising these linkers and preparing such controlled release systems.

  本发明涉及一种特定类别的可生物降解连接剂，确保构建块和/或生物活性化合物短暂稳定地结合成药物传递系统（DDS），例如基于聚合物微粒或水凝胶的DDS。此外，本发明涉及包括所述连接剂的化合物，此类化合物优选为前药。此外，本发明还涉及所述连接剂的使用，特别是所述可生物降解连接剂在药物传递系统中的使用。此外，本发明还涉及控制释放系统，包括聚合物基质，能够释放活性成分，其中所述活性成分通过所述连接剂共价连接到聚合物基质的聚合物分子上，以及一种合成这些连接剂和制备此类控制释放系统的方法。
• Tunable, biodegradable linker molecules for transient conjugation of components in drug delivery systems, and drug delivery systems prepared therewith
  申请人：Rijcken Cristianne Johanna Ferdinand

  公开号：US09339554B2

  公开（公告）日：2016-05-17

  The present invention relates to a particular class of biodegradable linkers, ensuring transiently stable conjugation of building blocks and/or bioactive compounds into drug delivery systems (DDS), such as DDS based on polymeric micelles or hydrogels. In addition, the present invention relates to compounds, comprising said linkers, such compounds preferably being prodrugs. Further, the invention is directed to the use of said linkers, and especially said biodegradable linkers, in a drug delivery system. Moreover, the invention relates to controlled release system comprising a polymer matrix, capable of releasing an active ingredient, wherein the active ingredient is covalently linked to the polymer molecules of the polymer matrix through said linkers, as well as to a method of synthesizing these linkers and preparing such controlled release systems.

  本发明涉及一种特定类别的可生物降解连接剂，确保建筑单元和/或生物活性化合物暂时稳定地结合成药物传递系统（DDS），例如基于聚合物微粒或水凝胶的DDS。此外，本发明涉及包含所述连接剂的化合物，这些化合物最好是前药。此外，本发明还涉及所述连接剂的使用，特别是所述可生物降解连接剂在药物传递系统中的使用。此外，本发明涉及一种控制释放系统，包括聚合物基质，能够释放活性成分，其中活性成分通过所述连接剂共价连接到聚合物基质的聚合物分子上，以及一种合成这些连接剂和准备这种控制释放系统的方法。
• High systemic availability of core-crosslinked polymeric micelles after subcutaneous administration
  作者：Qizhi Hu、Jai Prakash、Cristianne J.F. Rijcken、Wim E. Hennink、Gert Storm

  DOI：10.1016/j.ijpharm.2016.09.030

  日期：2016.11

  Covalent entrapment of drug molecules within core-crosslinked polymeric micelles (CCPM) represents an attractive approach to improve their therapeutic index. As an alternative to the most commonly employed intravenous (i.v.) route, subcutaneous (s.c.) administration offers the possibility of self-administration and thereby may reduce healthcare costs. The aim of this work was to assess the pharmacokinetic profile and systemic availability of drug-containing CCPM following s.c. injection. We here derivatised dexamethasone (DMS) with three different linkers, which enabled covalent attachment of this drug to the core of CCPM. The obtained DMS-containing CCPM exhibited varying drug release kinetics in vitro. Remarkably, a single dose of DMS-containing CCPM resulted in high systemic availability of about 30% following s.c. injection into the flank of healthy mice, as evidenced by an AUC between 26-37% relative to the AUC attained following i.v. injection. Although different linkers resulted in moderate variations in pharmacokinetic parameters, the overall pharmacokinetic profiles of these i.v. or s.c. administered nanomedicines were not substantially different. Next to DMS, we covalently attached paclitaxel (PTX) to the core of CCPM. Similarly, a single s.c. dose of PTX-containing CCPM resulted in high systemic availability of about 40% compared to i.v. injection and PTX (entrapped plus released) was detected in the blood for at least 3 days. Importantly, the systemic availability of s.c. administered drug-containing CCPM is substantially higher than that of other nanoformulations as reported in the literature (e.g. 3% in rodents). These results demonstrate that s.c. administration is a promising route to attain high systemic availability of CCPM, enabling a potentially more patient-friendly and cost-effective treatment approach than the i.v. route. (C) 2016 Elsevier B.V. All rights reserved.
• NANOPARTICLES WITH ACTIVE TARGETING
  申请人：Cristal Delivery B.V.

  公开号：EP3377047A1

  公开（公告）日：2018-09-26