3-(N-methacryloylglycylphenylalanylleucylglycyl)thiazolidine-2-thione | 831242-05-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(N-methacryloylglycylphenylalanylleucylglycyl)thiazolidine-2-thione
• 英文别名: N-methacryloylglycylphenylalanylleucylglycyl-thiazolidine-2-thione；MA-GFLG-TT；(2S)-4-methyl-2-[[(2S)-2-[[2-(2-methylprop-2-enoylamino)acetyl]amino]-3-phenylpropanoyl]amino]-N-[2-oxo-2-(2-sulfanylidene-1,3-thiazolidin-3-yl)ethyl]pentanamide
• CAS: 831242-05-8
• 化学式: C₂₆H₃₅N₅O₅S₂
• 分子量: 561.726
• InChiKey: ULSJFVFRBTYDGQ-PMACEKPBSA-N

物化性质

• 熔点：
  156-158 °C
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  194
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(N-methacryloylglycylphenylalanylleucylglycyl)thiazolidine-2-thione 、 盐酸吉西他滨 在 吡啶 作用下， 反应 12.0h， 以66.1%的产率得到N-methacyloylglycylphenylalanylleucylglycyl-gemcitabine
  参考文献：
  名称：

  Polymeric drug delivery conjugates and methods of making and using thereof

  摘要：

  本文描述了一种可降解的药物传递共轭物，用于有效地将生物活性剂传递给受试者。药物传递共轭物包括水溶性高分子量线性可降解聚合物骨架，该骨架包括通过第一（主链）可切割连接子连接在一起的多个线性水溶性聚合物段，其中生物活性剂与至少一个水溶性聚合物段、至少一个可切割连接子或二者的组合共价结合。这些共轭物相对于先前技术的传递共轭物具有许多优点。本文还描述了制备和使用这些共轭物的方法。

  公开号：

  US09289510B2
• 作为产物：
  描述：

  2-巯基噻唑啉 、 MA-GFLG-OH 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80 mg的产率得到3-(N-methacryloylglycylphenylalanylleucylglycyl)thiazolidine-2-thione
  参考文献：
  名称：

  聚合物抗肿瘤药靶向抗体片段通过线圈螺旋母题绑定：对小鼠BCL1白血病的体内治疗功效。

  摘要：

  一种BCL1靶向白血病细胞的高分子药物结合物，分子量分布窄，由N（2-羟丙基）甲基丙烯酰胺共聚物载体和抗癌药吡柔比星是通过受控的自由基共聚反应，然后进行无金属点击化学反应制得的。源自B1单克隆抗体的靶向重组单链抗体片段（scFv）通过两个互补肽之间的卷曲螺旋相互作用非共价附接到聚合物载体上。两对卷曲的螺旋形成肽（缩写为KEK / EKE和KSK / ESE）被用作聚合物-吡柔比星缀合物与靶向蛋白之间的接头。与其他缀合物相比，具有卷曲螺旋接头KSK / ESE的靶向聚合物缀合物在体外表现出4倍更好的细胞结合活性和2倍更高的细胞毒性。

  DOI：

  10.1002/mabi.201700173

文献信息

• POLYMERIC DRUG DELIVERY CONJUGATES AND METHODS OF MAKING AND USING THEREOF
  申请人：Kopecková Pavla

  公开号：US20130156722A1

  公开（公告）日：2013-06-20

  Described herein are biodegradable drug delivery conjugates for effectively delivering bioactive agents to a subject. The drug delivery conjugates comprise a water-soluble high molecular weight linear biodegradable polymer backbone comprising a plurality of linear water-soluble polymeric segments connected to one another by a first (main-chain) cleavable linker, wherein a bioactive agent is covalently bonded to at least one water-soluble polymeric segment, at least one cleavable linker, or a combination thereof. The conjugates possess numerous advantages over prior art delivery conjugates. Also described herein are methods for making and using the conjugates.

  本文描述了一种可生物降解的药物传递共轭物，用于有效地将生物活性物质传递给受试者。药物传递共轭物包括水溶性高分子量线性可生物降解聚合物骨架，该骨架包括通过第一（主链）可断裂连接剂相互连接的多个线性水溶性聚合物段，其中生物活性物质与至少一个水溶性聚合物段，至少一个可断裂连接剂或其组合共价键合。与先前的传递共轭物相比，这些共轭物具有许多优点。本文还描述了制备和使用这些共轭物的方法。
• Polymer Therapeutics with a Coiled Coil Motif Targeted against Murine BCL1 Leukemia
  作者：Robert Pola、Richard Laga、Karel Ulbrich、Irena Sieglová、Vlastimil Král、Milan Fábry、Martina Kabešová、Marek Kovář、Michal Pechar

  DOI：10.1021/bm3019592

  日期：2013.3.11

  The specificity of polymer conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) bearing cytostatic drugs for cancer cells could be significantly increased by the incorporation of a suitable targeting ligand, such as a monoclonal antibody (mAb). However, direct binding of the protein e polymer carrier could cause considerable problems, such as decreasing the binding capacity of mAb to its target. Here, we introduce a novel strategy of joining a targeting moiety to a polymeric conjugate with cytostatic drug. The scFv of B1 mAb (specific for BCL1 leukemia cells) was tagged with peptide K ((VAALKEK)(4)). Peptide E ((VAALEKE)(4)), which forms a stable coiled coil structure heterodimer with peptide K, was assembled with the HPMA copolymers bearing doxorubicin. Such targeted polymeric conjugates possess very selective and high binding activity toward BCL1 cells. Similarly, targeted polymeric conjugates exert approximately 100 times higher cytostatic activity toward BCL1 cells in comparison to nontargeted conjugates in vitro. At the same time, the conjugates have comparable and rather low cytostatic activity for 38C13 cells, which are used as a negative control, in vitro.
• Synthesis of biodegradable multiblock copolymers by click coupling of RAFT-generated heterotelechelic polyHPMA conjugates
  作者：Jiyuan Yang、Kui Luo、Huaizhong Pan、Pavla Kopečková、Jindřich Kopeček

  DOI：10.1016/j.reactfunctpolym.2010.10.005

  日期：2011.3

  A new strategy for the synthesis of biodegradable high molecular weight N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymeric carriers has been designed. An enzyme-sensitive, alkyne-functionalized, chain transfer agent (CTA-GFLG-alkyne; N-alpha-(4-pentynoyl)-N-delta-(4-cyano-4-(phenylcarbonothioylthio)pentanoyl-glycylphenylalanylleucylglycyl)-lysine) was synthesized and used to mediate the reversible addition-fragmentation chain transfer (RAFT) polymerization and copolymerization of HPMA. Post-polymerization modification with 4,4'-azobis(azidopropyl 4-cyanopentanoate) resulted in the formation of heterotelechelic HPMA copolymers containing terminal alkyne and azide groups. Chain extension via click reaction resulted in high molecular weight multiblock copolymers. Upon exposure to papain, these copolymers degraded into the initial blocks. Similar results were obtained for copolymers of HPMA with N-methacryloylglycylphenylalanylleucylglycyl thiazolidine-2-thione and N-methacryloyl-glycylphenylalanylleucylglycyl-gemcitabine. The new synthetic method presented permits the synthesis of biocompatible, biodegradable high molecular weight HPMA copolymer-anticancer drug conjugates that possess long-circulation times and augmented accumulation in solid tumor tissue due to the enhanced permeability and retention effect. (C) 2010 Elsevier Ltd. All rights reserved.
• HPMA-DRUG CONJUGATES FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA
  申请人：University of Utah Research Foundation

  公开号：US20180214560A1

  公开（公告）日：2018-08-02

  Disclosed are methods are of treating acute myeloid leukemia (AML) comprising administering an effective amount of a first AML therapeutic and an effective amount of a second AML therapeutic. Also disclosed are methods of treating AML comprising administering an effective amount of a first AML therapeutic conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer. Also disclosed are methods of treating AML comprising administering an effective amount of a first AML therapeutic conjugated to HPMA copolymer, wherein the first AML therapeutic conjugated to HPMA copolymer comprises a HPMA copolymer backbone comprising at least two HPMA copolymer segments connected by a degradable peptide sequence.
• US9289510B2
  申请人：——

  公开号：US9289510B2

  公开（公告）日：2016-03-22