N-(2-羟基丙基)甲基丙烯酰胺 | 40704-75-4

• 物质功能分类: 有机原料 - 氨基化合物 - 酰胺类化合物
• 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
• 中文名称: N-(2-羟基丙基)甲基丙烯酰胺
• 中文别名: N-(2-羟丙基)甲基丙烯酰胺
• 英文名称: N-(2-hydroxypropyl)methacrylamide
• 英文别名: HPMA；N-(2-hydroxypropyl)-2-methylprop-2-enamide
• CAS: 40704-75-4；21442-01-3
• 化学式: C₇H₁₃NO₂
• mdl: MFCD00080531
• 分子量: 143.186
• InChiKey: OKPYIWASQZGASP-UHFFFAOYSA-N

物化性质

• 熔点：
  67.92°C
• 沸点：
  321.2±34.0 °C(Predicted)
• 密度：
  1.002 g/mL ((predicted))
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

制备方法与用途

生物活性

N-(2-羟基丙基)甲基丙烯酰胺用于合成共聚物，并能在内脏利什曼病 (VL) 中靶向性递送抗衰老药物。

体内研究

在5 mg/kg体重的等效药剂量下，所有含有溶酶体可降解侧链的N-(2-羟基丙基)甲基丙烯酰胺共聚物-药物缀合物均表现出显著的体内抗利什曼原虫活性（大于99%抑制）。

反应信息

• 作为反应物：
  描述：

  N-(2-羟基丙基)甲基丙烯酰胺 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Biotinylated HPMA centered polymeric nanoparticles for Bortezomib delivery

  摘要：

  Bortezomib (BTZ) is a proteasome inhibitor as approved by US FDA for the treatment of multiple myeloma. It exhibits significant anti-cancer properties, against solid tumors; but lacks aqueous solubility, chemical stability which hinders its successful formulation development. The present study is an attempt to deliver BTZ using N-(2-hydroxypropyl) methacrylamide (HPMA) based copolymeric conjugates and biotinylated PNPs in an effective manner. Study describes a systematic synthetic pathway to synthesize functional polymeric conjugates such as HPMA-Biotin (HP-BT) HPMA-Polylactic acid (HPLA) and HPMA-PLA-Biotin (HPLA-BT) followed by exhaustive characterization both spectroscopically and microscopically. Our strategy yielded polymeric nanoparticles (PNPs) of narrow size range of 199.7 +/- 1.32 nm. Release studies were performed at pH 7.4 and 5.6. PNPs were 2-folds less hemolytic (p < 0.0001) than pure drug. BTZ loaded PNPs of HPLA-BT demonstrated significant anti-cancer activity against MCF-7 cells. IC50 value of these PNPs was 56.06 +/- 0.12 nM, which was approximately two folds less than BTZ (p < 0.0001). Cellular uptake study confirmed that higher uptake of formulations might be an outcome of biotin surface tethering characteristics that enhanced selectivity and targeting of formulations efficiently. In vivo pharmacokinetics evidenced increased bioavailability (AUC(0 t-infinity)) of DL-HPLA-BT PNPs (drug loaded) than BTZ with an improved half-life. Overall the developed PNPs led to the improved and effective BTZ delivery.

  DOI：

  10.1016/j.ijpharm.2020.119173
• 作为产物：
  描述：

  (S)-2-Hydroxy-propionic acid (S)-1-[1-methyl-2-(2-methyl-acryloylamino)-ethoxycarbonyl]-ethyl ester 在 phosphate buffer saline 作用下， 以 二甲基亚砜 为溶剂， 生成 N-(2-羟基丙基)甲基丙烯酰胺
  参考文献：
  名称：

  Degradation Mechanism and Kinetics of Thermosensitive Polyacrylamides Containing Lactic Acid Side Chains

  摘要：

  Diblock copolymers of poly(N-isopropylacrylamide-co-N-(2-hydroxypropyl)methacrylamide lactate) (poly(NIPAAm-co-HPMAm-lactate)) as a thermosensitive block and poly(ethylene glycol) (PEG) as a hydrophilic block form polymeric micelles above the cloud point (CP) of the temperature-sensitive block. Destabilization of these micelles occurs upon hydrolysis of the lactate side chains. Here we report on the degradation kinetics of the HPMAm-mono(di)lactate monomers and their copolymers with NIPAAm. The degradation of the monomers and polymers in their soluble state (thus below their CP) followed normal ester hydrolysis behavior: the degradation rate increased with temperature, pH (from pH 7.5 to 11), and dielectric constant of the medium. Above the CP, where the polymers are in a precipitated state, a significant retardation of the polymer degradation occurred due to a decrease of dielectric constant of the local environment of the precipitated polymer. This study shows that it is possible to predict the rate of formation of HPMAm in NIPAAm-co-HPAIAm-lactate copolymers which results in an increase of the overall hydrophilicity of the polymers and destabilization of polymeric micelles based on poly(NIPAAm-co-HPMAm-lactate).

  DOI：

  10.1021/ma034381n
• 作为试剂：
  描述：

  2-methyl-4-(4-(trifluoromethoxy)phenyl)oxazole 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 偶氮二异丁腈 、 N-(2-羟基丙基)甲基丙烯酰胺 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 thiazol-5-yl
  参考文献：
  名称：

  Design, synthesis and structure–activity relationships of substituted oxazole–benzamide antibacterial inhibitors of FtsZ

  摘要：

  The design, synthesis and structure-activity relationships of a series of oxazole-benzamide inhibitors of the essential bacterial cell division protein FtsZ are described. Compounds had potent anti-staphylococcal activity and inhibited the cytokinesis of the clinically-significant bacterial pathogen Staphylococcus aureus. Selected analogues possessing a 5-halo oxazole also inhibited a strain of S. aureus harbouring the glycine-to-alanine amino acid substitution at residue 196 of FtsZ which conferred resistance to previously reported inhibitors in the series. Substitutions to the pseudo-benzylic carbon of the scaffold improved the pharmacokinetic properties by increasing metabolic stability and provided a mechanism for creating pro-drugs. Combining multiple substitutions based on the findings reported in this study has provided small-molecule inhibitors of FtsZ with enhanced in vitro and in vivo antibacterial efficacy. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.002

文献信息

• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• HPMA POLYMER PLATINUM CHELATES
  申请人：Sood Paul

  公开号：US20110286958A1

  公开（公告）日：2011-11-24

  Polymeric platinum amidomalonate complexes, where the platinum is in +2 or +4 oxidation state, and where the complexes optionally contain tumor seeking groups, are useful in the treatment of cancer.

  聚合物铂胺基丙二酸盐络合物，其中铂处于+2或+4氧化态，且这些络合物可选择性地含有寻找肿瘤的基团，在癌症治疗中是有用的。
• Enzymatically Catalyzed Generation of Electronically Excited States in a Synthetic Copolymer with a Schiff Base in Pendant Groups
  作者：Robert Zoulík、Zdeněk Pavlíček、Jiří Vohlídal、Vladimír Šubr

  DOI：10.1135/cccc19950095

  日期：——

  The copolymer of N-(2-hydroxypropyl)methacrylamide and N-[N-(N-methacryloylglycyl)glycyl]hexane- 1,6-diamine (17.6 mole %) was prepared as a model compound for investigation of the mechanism of enzymatically catalyzed generation of electronically excited states in proteins. The amino end groups of the copolymer side chains were transformed into a Schiff base by reaction with glycolaldehyde. The modified copolymer was characterized by its ultraviolet, visible and fluorescence spectra. The enzymatically catalyzed oxidation of the modified copolymer was carried out in a phosphate buffer at pH 7 using horseradish peroxidase as the enzyme. The generation of electronically excited states was demonstrated by chemiluminescence measurement and by a spectroscopic procedure based on transfer of the excitation energy to bilirubin.

  N-(2-羟丙基)甲基丙烯酰胺和N-[N-(N-甲基丙烯酰基甘氨酰)甘氨酰]己烷-1,6-二胺（17.6摩尔%）的共聚物被制备为研究酶催化蛋白质中电子激发态生成机制的模型化合物。 共聚物侧链的氨基末端通过与甘醛反应转化为席夫碱。 经过改性的共聚物通过其紫外、可见和荧光光谱进行表征。 在pH 7的磷酸盐缓冲液中，使用辣根过氧化物酶作为酶，对改性共聚物进行酶催化氧化。 通过化学发光测量和基于将激发能量转移到胆红素的光谱程序，证明了电子激发态的生成。
• 一种基于N-(2-羟丙基)甲基丙烯酰胺聚合物 的纳米粒及其制备方法
  申请人：四川大学

  公开号：CN105412935B

  公开（公告）日：2019-02-19

  本发明公开了一种基于N‑(2‑羟丙基)甲基丙烯酰胺（HPMA）聚合物的可克服粘液屏障的纳米粒及其制备方法，该纳米粒由核壳两部分组成，其中，内核为生物相容性载体材料与活性成分所形成的纳米复合物，外壳则为HPMA聚合物及其衍生物。
• [EN] HALOGENATED HETEROALKENYL- AND HETEROALKYL-FUNCTIONALIZED ORGANIC COMPOUNDS AND METHODS FOR PREPARING SUCH COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES HALOGÉNÉS À FONCTION HÉTÉROALCÉNYLE ET HÉTÉROALKYLE ET LEURS PROCÉDÉS DE PRÉPARATION
  申请人：ARKEMA INC

  公开号：WO2019067394A1

  公开（公告）日：2019-04-04

  A method for synthesizing halogenated organic compounds, such as halogenated alkenyl group-containing and halogenated alkyl group-containing compounds having a heteroatom (e.g., O,N.S) coupled to a carbon atom of a halogenated alkenyl or halogenated alkyl group, involves reacting a halogenated olefin such as a chloro-substituted trifluoropropenyl compound with an active hydrogen-containing organic compound such as an alcohol (e.g., an aliphatic monoalcohol, aliphatic polyalcohol, or a phenolic compound), a primary amine, a secondary amine or a thiol.

  合成卤代有机化合物的方法，例如含卤代烯基基团和含卤代烷基基团的化合物，其中含有一个杂原子（例如，O，N，S）与卤代烯基或卤代烷基基团的碳原子偶联，涉及将卤代烯烃（例如氯代三氟丙烯基化合物）与含有活性氢的有机化合物（例如醇（例如脂肪族单醇，脂肪族多醇或酚类化合物），一级胺，二级胺或硫醇）反应。