D-folic acid | 65165-91-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: D-folic acid
• 英文别名: folic acid；N-pteroyl-D-glutamic acid；N-Pteroyl-D-glutaminsaeure；D-Folic Acid；(2R)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid
• CAS: 65165-91-5
• 化学式: C₁₉H₁₉N₇O₆
• 分子量: 441.403
• InChiKey: OVBPIULPVIDEAO-GFCCVEGCSA-N

物化性质

• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  10

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  N-羟基丁二酰亚胺 、 D-folic acid 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二甲基亚砜 为溶剂， 以86.4%的产率得到
  参考文献：
  名称：

  l-Buthionine Sulfoximine Detection and Quantification in Polyurea Dendrimer Nanoformulations

  摘要：

  l-Buthionine sulfoximine（l-BSO）是一种辅助药物，据报道可以增加癌细胞对新生物药物的敏感性。树状分子是优秀的药物传递系统，l-BSO纳米制剂被认为是潜在的化疗药物。低波长下对l-BSO的吸收限制了传统分析工具的检测。现在报道了一种简单而敏感的l-BSO检测和定量方法。在这项研究中，l-BSO被包封在以叶酸为靶向的第四代聚氨酯树状分子（PUREG4-FA2）中，并在pH 7.4和37°C下跟踪其释放曲线24小时。该方案使用原位l-BSO衍生化，通过儿茶酚衍生物的邻二酮形成，随后在503 nm处可见衍生物检测。通过NMR光谱法评估了所研究的l-BSO衍生物的结构。

  DOI：

  10.3390/molecules24173111
• 作为产物：
  描述：

  folate 在 亚硝酸特丁酯 、 1,1,2,3-四甲基胍 、 potassium thioacyanate 、 肼 作用下， 以 四氢呋喃 、 二甲基亚砜 、 三氟乙酸 为溶剂， 反应 29.5h， 生成 D-folic acid
  参考文献：
  名称：

  Efficient Syntheses of Pyrofolic Acid and Pteroyl Azide, Reagents for the Production of Carboxyl-Differentiated Derivatives of Folic Acid

  摘要：

  Reaction of folic acid (1) with excess trifluoroacetic anhydride provides access to both the previously unknown N-10-(trifluoroacetyl)pyrofolic acid (8) and pyrofolic acid (9). Reaction of either of these materials with hydrazine selectively affords pteroyl hydrazide (13), which may be oxidized to pteroyl azide (27) on a large scale (62% overall from 1 without the need for chromatography). Treatment of 27 with differentially protected glutamates provides a convenient and high-yielding synthesis of differentially protected, optically pure folates.

  DOI：

  10.1021/ja971568j

文献信息

• Multi-functional ionic liquid compositions for overcoming polymorphism and imparting improved properties for active pharmaceutical, biological, nutritional, and energetic ingredients
  申请人：Rogers D. Robin

  公开号：US20070093462A1

  公开（公告）日：2007-04-26

  Disclosed are ionic liquids and methods of preparing ionic liquid compositions of active pharmaceutical, biological, nutritional, and energetic ingredients. Also disclosed are methods of using the compositions described herein to overcome polymorphism, overcome solubility and delivery problems, to control release rates, add functionality, enhance efficacy (synergy), and improve ease of use and manufacture.

  揭示了离子液体及制备活性药物、生物、营养和能量成分的离子液体组合物的方法。还揭示了利用本文描述的组合物的方法，以克服多型性、克服溶解度和输送问题、控制释放速率、增加功能性、增强功效（协同作用）以及改善易用性和制造工艺。
• Folate-Decorated Amphiphilic Cyclodextrins as Cell-Targeted Nanophototherapeutics
  作者：Roberto Zagami、Valentina Rapozzi、Anna Piperno、Angela Scala、Claudia Triolo、Mariachiara Trapani、Luigi E. Xodo、Luigi Monsù Scolaro、Antonino Mazzaglia

  DOI：10.1021/acs.biomac.9b00306

  日期：2019.7.8

  Nowadays, active targeting of nanotherapeutics is a challenging issue. Here, we propose a rational design of a ternary nanoassembly (SAP) composed of nonionic amphiphilic β-cyclodextrins (amphiphilic CD) incorporating pheophorbide (Pheo) as a phototherapeutic and an adamantanyl-folic acid conjugate (Ada-FA) to target tumor cells overexpressing α-folate receptor (FR-α(+)). Dynamic light scattering and ζ-potential pointed out the presence of nanoassemblies bearing a negative surface charge (ζ = −51 mV). Morphology of SAP was investigated by atomic force microscopy and microphotoluminescence, indicating the presence of highly emissive near-spherical assemblies of about 280 nm in size. Complementary spectroscopic techniques such as ROESY-NMR, UV/vis and steady-state fluorescence revealed that the folic acid protrudes out of amphiphilic CD rims, prone for recognition with FR-α. Pheo was strongly loaded in the nanoassembly mostly in monomeric form, thus generating singlet oxygen (1O2) and consequentely showing phototherapeutic action. SAP remained stable until 2 weeks in aqueous solutions. Stability studies in biologically relevant media pointed out the ability of SAP to interact with serum proteins by means of the oligoethylenglycole fringe, without destabilization. Release experiments demonstrated the sustained release of Pheo from SAP in environments mimiking physiological conditions (∼20% within 1 week), plausibly suggesting low Pheo leaking and high integrity of the assembly within 24 h, time spent on average to reach the target sites. Cellular uptake of SAP was confirmed by confocal microscopy, pointing out that SAP was internalized into the tumoral cells expressing FR-α more efficiently than SP. SAP showed improved phototoxicity in human breast MCF-7 cancer cells FR-α(+) (IC50 = 270 nM) with respect to human prostate carcinoma PC3 cells (IC50 = 700 nM) that express a low level of that receptor (FR-α(−)). Finally, an improved phototoxicity in FR-α(+) MCF-7 cells (IC50 = 270 nM) was assessed after treatment with SAP vs SP (IC50 = 600 nM) which was designed without Ada-FA as a targeting unit.

  如今，主动靶向纳米治疗药物是一个具有挑战性的问题。在这里，我们提出了一个合理设计的由非离子型双亲性β-环糊精（双亲性CD）组成的三分子纳米组装体（SAP），其中包含了pheophorbide（Pheo）作为光治疗剂和adamantanyl-叶酸偶联物（Ada-FA），旨在靶向过度表达α-叶酸受体（FR-α(+)）的肿瘤细胞。动态光散射和ζ电位指出存在具有负表面电荷的纳米组装体（ζ = −51 mV）。通过原子力显微镜和微光致发光研究，表明存在大约280 nm大小的近球形高发光组装体。互补光谱技术如ROESY-NMR、紫外/可见光谱和稳态荧光揭示了叶酸突出于双亲性CD边缘，易于与FR-α识别。Pheo在纳米组装体中强烈负载，主要以单体形式存在，因此产生单线态氧（1O2），从而显示出光治疗作用。SAP在水溶液中保持稳定直至两周。在生物相关介质中的稳定性研究表明，SAP能够通过聚乙二醇边缘与血清蛋白相互作用，但不会导致不稳定。释放实验表明，在模拟生理条件的介质中，Pheo从SAP中持续释放（一周内约20%），可能暗示在24小时内Pheo泄漏较少，组装体完整性较高，这是到达目标位点的平均时间。通过共聚焦显微镜确认了SAP的细胞摄取，指出SAP在表达FR-α的肿瘤细胞中比SP更有效地被内化。与表达该受体水平较低的人前列腺癌PC3细胞（IC50 = 700 nM）相比，SAP在人乳腺癌MCF-7细胞FR-α(+)中显示出增强的光毒性（IC50 = 270 nM）。最后，在FR-α(+) MCF-7细胞中评估了SAP与SP相比在光毒性方面的改善（IC50 = 270 nM vs IC50 = 600 nM），后者设计时未包含Ada-FA作为靶向单元。
• METFORMIN FOLATE AND PREPARATION OF THE SAME
  申请人：Yie Hongping

  公开号：US20100105691A1

  公开（公告）日：2010-04-29

  The present invention discloses a novel biguanidine compound, i.e. folacin-metformin, and its manufacture with inorganic salt of metformin as raw material. Compared with metformin, the compound has the same clinic curative effect, such as lowering blood sugar, curing poly-cystic ovary syndrome (PCOS), losing weight and so on, without resulting in the increase of homocysteine concentration, even with a little decrease of homocysteine concentration in some cases.

  本发明揭示了一种新型双胍类化合物，即叶酸-二甲双胍，并以二甲双胍的无机盐为原料进行制备。与二甲双胍相比，该化合物具有相同的临床治疗效果，如降低血糖、治疗多囊卵巢综合症（PCOS）、减轻体重等，而不会导致同型半胱氨酸浓度的增加，甚至在某些情况下会略微降低同型半胱氨酸浓度。
• CONJUGATES OF NOSCAPINE AND FOLIC ACID AND THEIR USE IN TREATING CANCER
  申请人：Joshi Harish C.

  公开号：US20110286919A1

  公开（公告）日：2011-11-24

  The present invention is directed to compounds which are conjugates of two non-toxic natural products, noscapine (and various noscapine analogs) and folic acid (and various folic acid analogs), where the folic acid is conjugated to noscapine or the noscapine analog at the 9-position on the isoquinoline ring on the noscapine framework. Pharmaceutical compositions including the compounds, and methods of treating various tumors using the compounds and compositions, are also disclosed. The conjugates are particularly useful for treating cancers which overexpress the Folate Receptor α (FRa) receptor.

  本发明涉及两种非毒性天然产物，诺斯卡平（及各种诺斯卡平类似物）和叶酸（及各种叶酸类似物）的结合物，其中叶酸与诺斯卡平或诺斯卡平类似物在诺斯卡平框架上的异喹啉环的9位结合。还公开了包括该化合物的制药组合物以及使用该化合物和组合物治疗各种肿瘤的方法。这些结合物特别适用于治疗过度表达叶酸受体α（FRa）受体的癌症。
• Multi-Functional Ionic Liquid Compositions for Overcoming Polymorphism and Imparting Improved Properties for Active Pharmaceutical, Biological, Nutritional, and Energetic Ingredients
  申请人：Rogers Robin D.

  公开号：US20120264605A1

  公开（公告）日：2012-10-18

  Disclosed are ionic liquids and methods of preparing ionic liquid compositions of active pharmaceutical, biological, nutritional, and energetic ingredients. Also disclosed are methods of using the compositions described herein to overcome polymorphism, overcome solubility and delivery problems, to control release rates, add functionality, enhance efficacy (synergy), and improve ease of use and manufacture.

  本发明涉及离子液体和制备含有活性制药、生物、营养和能量成分的离子液体组合物的方法。同时，本发明还涉及使用所述组合物的方法，以克服多晶性、克服溶解度和输送问题、控制释放速率、增加功能、增强功效（协同作用）和改善使用和制造的便利性。