3-(3-methacrylamidopropanoyl)thiazolidine-2-thione | 920282-31-1

• 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-(3-methacrylamidopropanoyl)thiazolidine-2-thione
• 英文别名: N-methacryloyl-3-aminopropanoic acid thiazolidine-2-thione；2-methyl-N-[3-oxo-3-(2-sulfanylidene-1,3-thiazolidin-3-yl)propyl]prop-2-enamide
• CAS: 920282-31-1
• 化学式: C₁₀H₁₄N₂O₂S₂
• 分子量: 258.365
• InChiKey: QPCKLXWQFRRTAR-UHFFFAOYSA-N

物化性质

• 熔点：
  95-96 °C(Solv: ethyl acetate (141-78-6))
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-methacrylamidopropanoyl)thiazolidine-2-thione 、 炔丙胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.5h， 以69.5%的产率得到2-Methyl-N-[3-oxo-3-(prop-2-ynylamino)propyl]prop-2-enamide
  参考文献：
  名称：

  [EN] STAR POLYMER DRUG CONJUGATES
  [FR] CONJUGUÉS POLYMÈRE EN ÉTOILE-MÉDICAMENT

  摘要：

  一种星形聚合物，化学式为O[D1]-([X]-A(D2)-[Z]-[D3])n，其中O为核心；A为聚合物臂，包括反应性单体、亲水性单体和/或带电单体，并连接到核心；X为连接核心和聚合物臂的连接分子；Z为连接聚合物臂末端和D3的连接分子；D1为连接到核心的药物分子；D2为连接到沿着聚合物臂分布的反应性单体的药物分子；D3为连接到聚合物臂末端的药物分子；n为整数；[ ]表示该组是可选的；D2与沿聚合物臂分布的反应性单体以1 mol%至80 mol%的密度连接。

  公开号：

  WO2022086853A1
• 作为产物：
  描述：

  2-巯基噻唑啉 、 N-methacryloyl-3-aminopropanoic acid 在 4-二甲氨基吡啶 作用下， 生成 3-(3-methacrylamidopropanoyl)thiazolidine-2-thione
  参考文献：
  名称：

  通过重组抗体片段靶向GD2阳性肿瘤细胞的聚合物抗癌剂。

  摘要：

  设计，合成和表征了一种水溶性聚合物抗癌活性药物，该聚合物可有效靶向表达二唾液酸神经节苷脂抗原GD2的癌细胞。使用抗GD2单克隆抗体的重组单链片段（scFv），将抗肿瘤药物阿霉素与基于N-（2-羟丙基）甲基丙烯酰胺的共聚物的聚合物共轭物特异性靶向GD2抗原阳性的肿瘤细胞。靶向蛋白配体通过使用与反应性聚合物前体的传统非特异性氨解反应，通过蛋白质氨基之间的共价键，或通过共价连接至聚合物的Bungarotoxin之间的非共价但高度特异性的相互作用，连接到聚合物-药物偶联物上重组scFv经C端邦加毒素结合肽修饰。

  DOI：

  10.1021/acs.biomac.8b01616

文献信息

• [EN] COMPOSITIONS AND METHODS OF MANUFACTURING STAR POLYMERS FOR LIGAND DISPLAY AND/OR DRUG DELIVERY<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE FABRICATION DE POLYMÈRES EN ÉTOILE POUR L'AFFICHAGE DE LIGAND ET/OU L'ADMINISTRATION DE MÉDICAMENT
  申请人：AVIDEA TECH INC

  公开号：WO2020214858A1

  公开（公告）日：2020-10-22

  A star polymer of formula O[P1]-([X]-A[P2]-[Z]-[P3])n where O is a core; A is a polymer arm attached to the core; X is a linker molecule between the core and the polymer arm; Z is a linker molecule between the end of the polymer arm and P3; P1, P2 and P3 are each independently one or more pharmaceutically active compounds that act extracellularly or intracellularly, n is an integer number; [ ] denotes that the group is optional; and at least one of P1, P2 or P3 is present.

  一个星形聚合物的化学式为O[P1]-([X]-A[P2]-[Z]-[P3])n，其中O是一个核心；A是连接到核心的聚合物臂；X是核心和聚合物臂之间的连接分子；Z是连接到聚合物臂末端和P3之间的连接分子；P1、P2和P3分别是一个或多个药物活性化合物，可以在细胞外或细胞内起作用，n是一个整数；[ ]表示该组是可选的；并且至少有一个P1、P2或P3存在。
• Polymeric Conjugates of 9-[2-(Phosphonomethoxy)ethyl]purine with Potential Antiviral and Cytostatic Activity
  作者：Michal Pechar、Alena Braunová、Vladimír Šubr、Karel Ulbrich、Antonín Holý

  DOI：10.1135/cccc20061211

  日期：——

  Syntheses and characterization of polymer conjugates of 9-[2-(phosphonomethoxy)ethyl] (PME) derivatives of adenine (PMEA), 2,6-diaminopurine (PMEDAP) and guanine (PMEG) are described. The phosphonate group of these acyclic nucleotide analogues was activated by reaction with triphenylphosphine and di(2-pyridyl) disulfide (TPP-PDS). The activated phosphonate reacted with a random copolymer containing N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-methacrylamidopropanoyl)ethane-1,2-diamine (Ma-AP-ED) units. The phosphonamide bond between the nucleotide and polymer carrier proved to be relatively stable at physiological pH 7.4 while at pH 5.0 (corresponding to endosomal or lysosomal compartments of cells) underwent slow hydrolysis. The rate of hydrolysis (drug release) was shown to depend on the detailed structure of the heterocyclic base. The polymer-drug conjugates described in the paper represent a new family of antiviral and cytostatic drugs with potentially improved pharmacokinetics, sustained drug release and diminished non-specific toxicity.

  描述了腺嘌呤（PMEA）的9-[2-(磷酸甲氧基)乙基]（PME）、2,6-二氨基嘌呤（PMEDAP）和鸟嘌呤（PMEG）的聚合物共轭物的合成和表征。这些开链核苷类似物的磷酸酯基通过与三苯基膦和二(2-吡啶基)二硫化物（TPP-PDS）反应而被激活。激活的磷酸酯基与含有N-(2-羟基丙基)甲基丙烯酰胺（HPMA）和N-(3-甲基丙烯酰胺基)乙烷-1,2-二胺（Ma-AP-ED）单元的随机共聚物发生反应。核苷和聚合物载体之间的磷酰胺键在生理pH 7.4下被证明相对稳定，而在pH 5.0（对应于细胞内的内体或溶酶体区）时发生缓慢水解。水解速率（药物释放）被证明取决于杂环碱基的详细结构。文章中描述的聚合物-药物共轭物代表了一类新的抗病毒和抗细胞增生药物，具有潜在改进的药代动力学、持续的药物释放和降低的非特异性毒性。
• [EN] GLYCOPOLYMER, METHOD OF PREPARATION THEREOF, USE THEREOF AS MEDICAMENT<br/>[FR] GLYCOPOLYMÈRE, SON PROCÉDÉ DE PRÉPARATION, SON UTILISATION EN TANT QUE MÉDICAMENT
  申请人：USTAV MAKROMOLEKULARNI CHEMIE AV CR V V I

  公开号：WO2021047699A1

  公开（公告）日：2021-03-18

  The invention relates to multivalent glycopolymers based on HPMA polymers (copolymers or homopolymers) with carbohydrate structures containing a terminal monosaccharide in the galacto-configuration, which are effective as galectin inhibitors. These glycopolymers can be used as drugs for the therapy and prevention of oncological diseases associated with overproduction of galectins, especially of human galectin-3 (Gal-3).

  该发明涉及基于HPMA聚合物（共聚物或同聚物）的多价糖聚合物，其含有以半乳糖构型为终端的碳水化合物结构，可作为半乳糖凝集素抑制剂。这些糖聚合物可用作治疗和预防与过度产生凝集素有关的肿瘤性疾病的药物，特别是人类凝集素-3（Gal-3）。
• [EN] COMPOSITIONS AND METHODS OF MANUFACTURING AMPHIPHILIC BLOCK COPOLYMERS THAT FORM NANOPARTICLES IN SITU<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE FABRICATION DE COPOLYMÈRES SÉQUENCÉS AMPHIPHILES QUI FORMENT DES NANOPARTICULES IN SITU
  申请人：AVIDEA TECH INC

  公开号：WO2022066635A1

  公开（公告）日：2022-03-31

  An amphiphilic block copolymer having any one of the formulas D-S-H, S(D)-H, S-H(D), D-S-H-S, D-S-H-S-D, S(D)-H-S, S(D)-H-S(D) or S-H(D)-S is disclosed. S is a hydrophilic block; H is a hydrophobic block; D is a drug molecule; ( ) denotes that the group is bonded directly or indirectly as a side chain or as part of a side chain group to the adjacent group; and the hyphen, "-" (or sometimes "–"), denotes that each of the adjacent S, H or D are linked either directly to one another or indirectly to one another via a linker, additionally wherein the hydrophilic block comprises a first hydrophilic monomer and the hydrophobic block comprises a first hydrophobic monomer and a second hydrophobic monomer.

  本发明公开了一种具有以下任一公式之一的两亲性嵌段共聚物：D-S-H，S（D）-H，S-H（D），D-S-H-S，D-S-H-S-D，S（D）-H-S，S（D）-H-S（D）或S-H（D）-S。其中，S是亲水性块；H是疏水性块；D是药物分子；（）表示该基团直接或间接地作为侧链或侧链基团之一与相邻基团连接；连字符“-”（有时为“–”）表示相邻的S、H或D之间通过连接基团直接或间接连接在一起。此外，亲水性块包括第一亲水性单体，疏水性块包括第一疏水性单体和第二疏水性单体。
• Polymer-Antimicrobial Peptide Constructs with Tailored Drug-Release Behavior
  作者：Robert Pola、Matěj Vícha、Jiří Trousil、Eliška Grosmanová、Michal Pechar、Anna Rumlerová、Martin Studenovský、Emilie Kučerová、Pavel Ulbrich、Barbora Vokatá、Tomáš Etrych

  DOI：10.3390/pharmaceutics15020406

  日期：——

  Microbial resistance is one of the main problems of modern medicine. Recently, antimicrobial peptides have been recognized as a novel approach to overcome the microbial resistance issue, nevertheless, their low stability, toxicity, and potential immunogenic response in biological systems have limited their clinical application. Herein, we present the design, synthesis, and preliminary biological evaluation of polymer-antibacterial peptide constructs. The antimicrobial GKWMKLLKKILK-NH2 oligopeptide (PEP) derived from halictine, honey bee venom, was bound to a polymer carrier via various biodegradable spacers employing the pH-sensitive or enzymatically-driven release and reactivation of the PEP’s antimicrobial activity. The antibacterial properties of the polymer-PEP constructs were assessed by a determination of the minimum inhibitory concentrations, followed by fluorescence and transmission electron microscopy. The PEP exerted antibacterial activity against both, gram-positive and negative bacteria, via disruption of the bacterial cell wall mechanism. Importantly, PEP partly retained its antibacterial efficacy against Staphylococcus epidermidis, Escherichia coli, and Acinetobacter baumanii even though it was bound to the polymer carrier. Indeed, to observe antibacterial activity similar to the free PEP, the peptide has to be released from the polymer carrier in response to a pH decrease. Enzymatically-driven release and reactivation of the PEP antimicrobial activity were recognized as less effective when compared to the pH-sensitive release of PEP.

  微生物耐药性是现代医学的主要问题之一。最近，抗菌肽被认为是克服微生物耐药性问题的一种新方法，然而，其在生物系统中的低稳定性、毒性和潜在免疫原性反应限制了其临床应用。在此，我们介绍了聚合物抗菌肽构建体的设计、合成和初步生物学评估。抗菌肽 GKWMKLLKKILK-NH2 寡肽（PEP）来源于蜜蜂毒液 halictine，通过各种可生物降解的间隔物与聚合物载体结合，利用 pH 值敏感性或酶驱动释放和重新激活 PEP 的抗菌活性。聚合物-PEP 构建物的抗菌特性是通过测定最低抑菌浓度以及荧光和透射电子显微镜来评估的。PEP 通过破坏细菌细胞壁机制，对革兰氏阳性和阴性细菌都具有抗菌活性。重要的是，即使 PEP 与聚合物载体结合，它对表皮葡萄球菌、大肠杆菌和鲍曼不动杆菌的抗菌效力仍部分保持不变。事实上，要观察到与游离 PEP 类似的抗菌活性，肽必须在 pH 值降低时从聚合物载体中释放出来。与对 pH 值敏感的 PEP 释放相比，酶促释放和重新激活 PEP 抗菌活性的效果较差。