N,N-diethyl-2-hydroxynicotinamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N,N-diethyl-2-hydroxynicotinamide
• 英文别名: 2-Hydroxy-n,n-diethylnicotinamide；N,N-diethyl-2-oxo-1H-pyridine-3-carboxamide
• 化学式: C₁₀H₁₄N₂O₂
• 分子量: 194.233
• InChiKey: LEQLJLMGZRVDSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N,N-diethyl-2-hydroxynicotinamide 、 4-(氯甲基)苯甲基醇 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 20.0h， 以90.3%的产率得到N,N-diethyl-2-((4-(hydroxymethyl)benzyl)oxy)nicotinamide
  参考文献：
  名称：

  NOVEL POLYMER-BASED HYDROTROPES FOR HYDROPHOBIC DRUG DELIVERY

  摘要：

  聚合物共轭物的特征在于聚合物的主链是阴离子聚合物，疏水基团被共价连接到聚合物主链上，用于制备药物封装的聚合物水热溶剂和组合物。这种材料在将药物输送到细胞中的方法以及用于治疗和缓解癌症等疾病和疾病是有用的。

  公开号：

  US20150283253A1
• 作为产物：
  描述：

  2-羟基烟酸 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 N,N-diethyl-2-hydroxynicotinamide
  参考文献：
  名称：

  摘要：

  Purpose. To identify hydrotropic agents that can increase aqueous paclitaxel (PTX) solubility and to study the chemical structures necessary for hydrotropic properties so that polymeric hydrotropic agents can be synthesized.Methods. More than 60 candidate hydrotropic agents (or hydrotropes) were tested for their ability to increase the aqueous PTX solubility. A number of nicotinamide analogues were synthesized based on the observation that nicotinamide showed a favorable hydrotropic property. The identified hydrotropes for PTX were used to examine the structure-activity relationship.Results. N,N-Diethylnicotinamide (NNDENA) was found to be the most effective hydrotropic agent for PTX. The aqueous PTX solubility was 39 mg/ml and 512 mg/ml at NNDENA concentrations of 3.5 M and 5.95 M, respectively. These values are 5-6 orders of magnitude greater than the intrinsic solubility of 0.30+/-0.02 mug/ml. N-Picolylnicotinamide, N-allylnicotinamide, and sodium salicylate were also excellent hydrotropes for PTX. Solubility data showed that an effective hydrotropic agent should be highly water soluble while maintaining a hydrophobic segment.Conclusions. The present study identified several hydrotropic agents effective for increasing aqueous solubility of PTX and analyzed the structural requirements for this hydrotropic property. This information can be used to find other hydrotropic compounds and to synthesize polymeric hydrotropes that are effective for PTX and other poorly water-soluble drugs.

  DOI：

  10.1023/a:1024458206032

文献信息

• Hydrotropic polymer-based paclitaxel-loaded self-assembled nanoparticles: preparation and biological evaluation
  作者：Lipeng Gao、Liefang Gao、Mingxue Fan、Qilong Li、Jiyu Jin、Jing Wang、Weiyue Lu、Lei Yu、Zhiqiang Yan、Yiting Wang

  DOI：10.1039/c7ra04563h

  日期：——

  The poor compatibility of carrier materials with drugs is one of the main obstacles in the drug encapsulation of nano-drug delivery system (NDDS), hindering the clinical translation of NDDS. In this study, using paclitaxel (PTX) as the insoluble model drug, we conjugated N,N-diethylniacinamide (DENA), a hydrotropic agent of PTX, to the backbone of poly(L-γ-glutamyl-glutamine) (PGG), a water-soluble

  载体材料与药物的相容性差是纳米药物递送系统（NDDS）的药物封装中的主要障碍之一，从而阻碍了NDDS的临床翻译。在这项研究中，使用紫杉醇（PTX）作为不溶性模型药物，我们将PTX的亲水剂N，N-二乙基烟酰胺（DENA）与聚（L -γ-谷氨酰胺-谷氨酰胺）（PGG）的骨架缀合，水溶性聚合物，以制备“水溶聚合物” PGG-DENA，以提高其与PTX的相容性。凭借DENA基团的水溶作用，PTX被PGG-DENA封装，从而得到水溶聚合物纳米颗粒（PGG-DENA / PTX NPs）。PTX共轭聚（L先前报道的-γ-谷氨酰胺-谷氨酰胺酸（PGG-PTX）NP被用作研究的对照。PGG–DENA / PTX NPs的z平均流体动力学直径约为70 nm，并且在PBS溶液中4°C时具有良好的长期稳定性。PGG-DENA / PTX NPs在96 h时PTX的累积释放率为79.10％，而PGG-PTX NPs的PTX累积释放率为22
• Polymer-based hydrotropes for hydrophobic drug delivery
  申请人：Nitto Denko Corporation

  公开号：US10080737B2

  公开（公告）日：2018-09-25

  Polymer conjugates characterized in that the backbone of the polymer is an anionic polymer and hydrophobic moieties are covalently attached to the polymer backbone are useful for preparing drug encapsulated polymer hydrotropes and compositions. Such materials are useful in methods for delivering the drug into cells, and for the treatment and alleviation of diseases and disorders such as cancer.

  聚合物共轭物的特点是聚合物的骨架是阴离子聚合物，疏水分子共价连接到聚合物骨架上，这种共轭物可用于制备药物包封聚合物水托品和组合物。这种材料适用于将药物输送到细胞中的方法，也适用于治疗和缓解癌症等疾病。
• POLYMER-BASED HYDROTROPES FOR HYDROPHOBIC DRUG DELIVERY
  申请人：Nitto Denko Corporation

  公开号：EP3129425B1

  公开（公告）日：2019-04-10
• Pharmaceutical applications of hydrotropic polymer micelles
  申请人：Lee Cheon Sang

  公开号：US20050158271A1

  公开（公告）日：2005-07-21

  Hydrotropic polymer micelles effective for increasing the water solubility of poorly soluble drugs are described. Such hydrotropic polymer micelles have the combined properties of polymer micelles and hydrotropic agents, which display a synergistic effect for increasing the solubility of such drugs. Hydrotropic polymer micelles are formed in solution from amphiphilic copolymers that comprise a hydrophilic polymer and a hydrophobic polymer having pendant hydrotropic agents. A preferred copolymer is a di-, tri- or multi-block copolymer composed of hydrophilic and hydrophobic polymer chains. A particularly preferred hydrophilic chain comprises polyethyleneoxide (PEG) and a preferred hydrophobic chain comprises hydrotropic monomer units derived from nicotinamide. The micelles are found to be much more effective in solubilizing poorly soluble drugs and exhibit an excellent long-term stability even at high loading of drugs. A hydrotropic polymer micelle has nanometer scale size, by which they can deliver poorly soluble drugs to the body through diverse routes of administration.
• [EN] PHARMACEUTICAL APPLICATIONS OF HYDROTROPIC AGENTS, POLYMERS THEREOF, AND HYDROGELS THEREOF<br/>[FR] APPLICATIONS PHARMACEUTIQUES D'AGENTS HYDROTROPES, POLYMERES ET HYDROGELS DE CES DERNIERS
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2002030466A2

  公开（公告）日：2002-04-18

  The present invention is directed to compounds effective for increasing the water solubility of poorly soluble drugs. Hydrotropic agents are identified, such as for increasing the solubility of paclitaxel. Polymerizable monomers of the hydrotropic agents are prepared and hydrotropic polymers formed from such monomers are generated. Both the monomers and resulting polymers increase the solubility of poorly soluble drugs. In some cases, the hydrotropic polymers are more effective at increasing solubility at low concentrations relative to a corresponding amount of the hydrotropic agent precursor. Additionally, the hydrotropic polymers (hytrops) can be crosslinked to yield hydrotropic hydrogels (hytrogels) capable of solubilizing a drug. The hytrogels can further be employed to generate micro-and nano-particle suspensions of a poorly soluble drug. The water solubility of paclitaxel can be increased by four orders of magnitude using compounds of the invention. Large molecular weight compounds, such as the hytrops and hytrogels, are expected to have low levels of absorption in the gastrointestinal tract, thereby making them particularly preferred for oral delivery of poorly soluble drugs.