sulfadimethoxine methacrylamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: sulfadimethoxine methacrylamide
• 英文别名: methacryloyl sulfadimethoxine；N-[4-[(2,6-dimethoxypyrimidin-4-yl)sulfamoyl]phenyl]-2-methylprop-2-enamide
• 化学式: C₁₆H₁₈N₄O₅S
• 分子量: 378.409
• InChiKey: VCNRCBDLBHKVML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  磺胺二甲氧嗪 、 甲基丙烯酰氯 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 以85%的产率得到sulfadimethoxine methacrylamide
  参考文献：
  名称：

  Drug pH-Sensitive Release in Vitro and Targeting Ability of Polyamidoamine Dendrimer Complexes for Tumor Cells

  摘要：

  最近，树枝状聚合物被广泛应用于药物输送和基因转染等医疗领域。本研究合成了一种对 pH 值敏感的聚甲基丙烯酰磺基二甲氧基（PSD）和乳糖修饰的聚乙二醇（PEG）二嵌段共聚物（LA-PEG-b-PSD）。还测量了 LA-PEG-b-PSD 的 pKa 值。然后，通过静电作用制备了 PAMAM (G4.0) 和 LA-PEG-b-PSD 的聚氨基胺 (PAMAM) 复合物。为了研究药物在体外对 pH 值敏感的释放，在 PAMAM 中添加了多柔比星（DOX）。在 pH 值为 6.5 的磷酸盐缓冲盐水（PBS）中，LA-PEG-b-PSD/PAMAM 复合物的药物累积释放率高于 pH 值为 7.4 的情况。通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MTT）测定法和共聚焦显微镜研究了 PAMAM 复合物的细胞毒性和细胞吸收情况。在 pH 值为 7.4 的条件下，LA-PEG-b-PSD/PAMAM/DOX 复合物能够增强 DOX 对 HepG2 细胞的细胞毒性。共聚焦显微镜显示，在 pH 值为 6.5 时，PEG-b-PSD/PAMAM 复合物的细胞吸收率更高。在 pH 值为 7.4 时，经乳糖修饰的 PAMAM 复合物对肝癌细胞的亲和力高于不含乳糖的复合物。这些结果表明，LA-PEG-b-PSD/PAMAM 复合物对 HepG2 细胞具有选择性靶向和细胞毒性。体内抗肿瘤研究表明，与非靶向 PAMAM/DOX 和 DOX 溶液相比，LA-PEG-b-PSD/PAMAM/DOX 复合物具有更高的抗肿瘤效力。这些结果表明，这种策略可用于治疗肝癌。

  DOI：

  10.1248/cpb.59.63

文献信息

• Synthesis of a PEGylated Polymeric pH Sensor and Its pH Sensitivity by Fluorescence Resonance Energy Transfer
  作者：Sung Woo Hong、Cheol-Hee Ahn、June Huh、Won Ho Jo

  DOI：10.1021/ma061175h

  日期：2006.10.1

  A new pH-sensitive polymeric sensor with dispersion stability and biocompatibility is synthesized, and its pH sensitivity is examined on the basis of the fluorescence resonance energy transfer (FRET) efficiency. The polymeric pH sensor has a FRET donor and a FRET acceptor attached to both ends of a pH-sensitive polymeric linker and is also PEGylated to enhance the dispersion stability in aqueous media and biocompatibility. The pH sensor emits the blue color corresponding to the emission of the FRET donor at pHs higher than 7.6, but the pH sensor emits the green color corresponding to the emission of the FRET acceptor at pHs lower than 6.8 when both samples are irradiated at 330 nm, indicating that lowering the pH from 7.6 to 6.8 induces the FRET due to the conformational change of polymeric linker from coil to globule.
• pH-responsive lipid core micelles for tumour targeting
  作者：Elena Ravazzolo、Stefano Salmaso、Francesca Mastrotto、Sara Bersani、Elena Gallon、Paolo Caliceti

  DOI：10.1016/j.ejpb.2012.11.002

  日期：2013.4

  A new acid-sensitive drug-delivery nanocarrier has been developed for tumour targeting. The self-assembling co-polymer stearoyl-PEG-poly-sulfadimethoxine methacrylate (stearoyl-PEG-polySDM) was prepared to obtain micelles with responsive behaviour in the physiopathologic pH range. Stearoyl-PEG-polySDM was synthesised using a multi-step procedure that includes pH-sensitive sulfadimethoxine methacrylate polymerisation by AGET-ATRP at the amino terminal side of stearoyl-PEG-NH2. Chemical analysis showed that the stearoyl-PEG-polySDM co-polymer contained a mean of seven methacryloyl sulfadimethoxines per molecule. Potentiometric and turbidimetric analyses showed that stearoyl-PEG-polySDM has an apparent pK(a) of 7.2 and a cloud point at pH 7.0. In water at pH 7.4, the co-polymer assembled spontaneously into 13.2 +/- 3.1 nm micelles with a critical micelle concentration (CMC) of 36 mu M. Cell-culture studies showed that the material was more biocompatible with respect to the control Brij-700 (R). The paclitaxel loading capacity of the micelles was 3.25 +/- 0.25% (w/w, %). The colloidal formulations were stable at pH 7.4 for several hours, while at pH 6.5, they rapidly rearranged and aggregated. Fluorescence spectroscopic and cytofluorimetric studies showed that the incubation of MCF-7 tumour cells with fluorescein-labelled stearoyl-PEG-polySDM at pH 6.5 resulted in massive time-dependent cell association, while the incubation at pH 7.4 showed significantly lower cell interaction. Confocal microscopy confirmed that at pH 6.5, the micelles are taken up by cells and that the fluorescein-labelled stearoyl-PEG-polySDM is distributed into the cytosol. At pH 6.5, paclitaxel-loaded stearoyl-PEG-polySDM micelles had a higher cytotoxic effect than the micelles incubated at pH 7.4. The former displayed similar cytotoxic activity to free paclitaxel. (C) 2012 Elsevier B.V. All rights reserved.
• Tunable pH- and CO₂-Responsive Sulfonamide-Containing Polymers by RAFT Polymerization
  作者：Brooks A. Abel、Michael B. Sims、Charles L. McCormick

  DOI：10.1021/acs.macromol.5b01453

  日期：2015.8.25

  The controlled RAFT polymerization of a library of pH- and CO2-responsive methacryloyl sulfonamides (MSAs) that possess pK(a) values in the biologically relevant regime (pH = 4.5-7.4) is reported. Initial polymerizations were conducted at 70 degrees C in DMF with 4-cyano-4-(ethylsulfanylthiocarbonylsulfanyl)pentanoic acid (CEP) or 4-cyanopentanoic acid dithiobenzoate (CTP), resulting in polymers of broad molecular weight distributions (K-w/M-n > 1.20). As well, chain extension of a poly(methacryloyl sulfacetamide) (pSAC) macro-CTA at 70 degrees C was unsuccessful, indicating a loss of "living" chain ends during polymerization. However, by conducting the RAFT polymerization of MSAs at 30 degrees C with 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile), polymers with narrow molecular weight distributions (M-w/M-n < 1.15) and improved chain end retention were obtained. Homopolymers of each MSA derivative were synthesized, and the influence of the sulfonamide R group on monomer pK(a) and pH-dependent polymer solubility was determined during these studies. The facility by which these controlled poly(MSAs) can be prepared via low-temperature RAFT without the need for functional group protection and the resulting pK(a)-dependent pH- and CO2-responsive properties point to significant potential in areas including drug and gene delivery and environmental remediation.