N-[4-(甲基氨基)苯甲酰基]-L-谷氨酸 | 52980-68-4

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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-[4-(甲基氨基)苯甲酰基]-L-谷氨酸
• 英文名称: p-(N-methylamino)benzoyl-L-glutamic acid
• 英文别名: N-Me-pAB-Glu；N-(4-methylamino-benzoyl)-L-glutamic acid；N-(4-Methylamino-benzoyl)-L-glutaminsaeure；N-[4-(methylamino)-benzoyl]-L-glutamic acid；p-(N-methyl)-aminobenzoyl-L-glutamic acid；L-(4-N-Methylaminobenzoyl)-glutaminsaeure；N-(p-(Methylamino)benzoyl)glutamic acid；(2S)-2-[[4-(methylamino)benzoyl]amino]pentanedioic acid
• CAS: 52980-68-4
• 化学式: C₁₃H₁₆N₂O₅
• 分子量: 280.28
• InChiKey: UFBUCKLNZUNJHS-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  N-[4-(甲基氨基)苯甲酰基]-L-谷氨酸 在 sodium hydroxide 、 碘 、 溶剂黄146 、 potassium iodide 作用下， 生成 2-[[4-[(2-氨基-4-氧代-1H-蝶啶-6-基)甲基-甲基氨基]苯甲酰基]氨基]戊烷二酸
  参考文献：
  名称：

  Analogs of Pteroylglutamic Acid. III. 4-Amino Derivatives

  摘要：

  DOI：

  10.1021/ja01173a061
• 作为产物：
  描述：

  3-[3-((allyloxy)carbonyl)-5-oxo-1,3-oxazolan-4-yl]propanoic acid 在 四(三苯基膦)钯 1,1,2,3-四甲基胍 、 sodium 、 二乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 N-[4-(甲基氨基)苯甲酰基]-L-谷氨酸
  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

• Photohydrolysis of Methotrexate Produces Pteridine, Which Induces Poly-G–specific DNA Damage Through Photoinduced Electron Transfer¶
  作者：Kazutaka Hirakawa、Masahiro Aoshima、Yusuke Hiraku、Shosuke Kawanishi

  DOI：10.1562/0031-8655(2002)076<0467:pomppw>2.0.co;2

  日期：——

  32P-labeled DNA fragments obtained from a human gene. Photoirradiated MTX caused DNA cleavage specifically at the underlined G in 5′-\underlineGG and 5′-G\underlineGG sequences in double-stranded DNA only when the DNA fragments were treated with piperidine, which suggests that DNA cleavage was caused by base modification with little or no strand breakage. With denatured single-stranded DNA the damage

  摘要 甲氨蝶呤 (MTX) 是一种抗肿瘤剂，具有光毒性。使用从人类基因获得的 32P 标记的 DNA 片段检查了光照射 MTX 对生物大分子的损伤机制。只有当 DNA 片段用哌啶处理时，光照射的 MTX 才会在双链 DNA 中的 5'-\underlineGG 和 5'-G\underlineGG 序列中的下划线 G 处引起 DNA 切割，这表明 DNA 切割是由碱基修饰引起的很少或没有断线。对于变性的单链 DNA，大多数鸟嘌呤残基都会发生损伤。双链DNA中2'-脱氧鸟苷的氧化产物8-羟基-2'-脱氧鸟苷（8-oxodGuo）的形成量超过单链DNA。这些结果表明光照射的 MTX 通过电子转移参与了双链 DNA 中 5'-\underlineGG 和 5'-G\underlineGG 序列中下划线 G 处的 8-oxodGuo 形成，然后 8-oxodGuo 进一步氧化成哌啶-不稳定的产品。
• Drug evolution: drug design at hot spots
  申请人：Konishi Yasuo

  公开号：US20060110743A1

  公开（公告）日：2006-05-25

  A new method of designing and generating compounds having an increased probability of being drugs, drug candidates, or biologically active compounds, in particular having a therapeutic utility, is disclosed. The method consists of identifying a group of bioactive compounds, preferably of diverse therapeutic uses or biological activities and built on a common building block. In this group of compounds, side chains modifying the building block are identified and used to generate a second set of compounds according to the proposed methods of hybridization”, “single substitution” or “incorporation of frequently used side chains”. If the compounds in the second set built on the same building block contain an unusually large number of drugs, preferably with diverse therapeutic uses or biological activities, they constitute a “hot spot”. A focused combinatorial library of the “hot spot” is then generated, preferably by methods of combinatorial chemistry, and compounds of this library are screened for a variety of therapeutic uses or biological activities. The method generates drugs, drug candidates, or biologically active compounds with a high probability, without requiring any prior knowledge of biological targets.

  本文揭示了一种设计和生成化合物的新方法，这些化合物具有成为药物、药物候选物或生物活性化合物的概率增加，特别是具有治疗效用。该方法包括识别一组生物活性化合物，最好是具有不同治疗用途或生物活性，并建立在共同的基础上。在这组化合物中，识别修改基础结构的侧链，并使用“杂交”、“单一替换”或“纳入常用侧链”的建议方法生成第二组化合物。如果第二组化合物建立在相同的基础结构上，包含异常数量的药物，最好是具有不同治疗用途或生物活性，它们构成一个“热点”。然后通过组合化学的方法生成一个专注的组合式库，其中包括“热点”的化合物，并对该库中的化合物进行各种治疗用途或生物活性的筛选。该方法生成的药物、药物候选物或生物活性化合物具有高概率，无需任何先前的生物靶标知识。
• 4(3H)-Oxo-5,6,7,8,-Tetrahydropyrido-(2,3-d)Pyrimidine derivatives
  申请人：THE TRUSTEES OF PRINCETON UNIVERSITY

  公开号：EP0255228A1

  公开（公告）日：1988-02-03

  The invention pertains to derivatives of N-[4-(N-[2-amino-4(3H)-oxo-5,6,7,8-tetrahydropyrido­[2,3-d]pyrimidin-6-ylmethyl]amino)benzoyl]-L-glutamic acid of the formula: wherein       R¹ is hydrogen, methyl, ethyl, or R⁵CO-;       R2ʹ and R3ʹ are hydrogen or a carboxylic acid protecting group;       R4ʹ is hydrogen or an amino protecting group; and       R⁵ is hydrogen or alkyl and the configuration about the carbon atom designated * is L, which derivatives are antineoplastic agents, to their preparation and use, and to intermediates useful in their preparation.

  本发明涉及 N-[4-(N-[2-氨基-4(3H)-氧代-5,6,7,8-四氢吡啶并[2,3-d]嘧啶-6-基甲基]氨基)苯甲酰基]-L-谷氨酸的衍生物，其式如下： 其中 R¹是氢、甲基、乙基或R⁵CO-； R2ʹ和 R3ʹ是氢或羧酸保护基团； R4ʹ 是氢或氨基保护基；以及 R⁵是氢或烷基，围绕碳原子的构型 * 是 L，这些衍生物是抗肿瘤剂，它们的制备和使用，以及制备过程中有用的中间体。
• 5-Amino-4-imidazolecarboxamide riboside and its nucleobase as potentiators of antifolate transport and metabolism
  申请人：McGuire J. John

  公开号：US20060160751A1

  公开（公告）日：2006-07-20

  The present invention provides a method for increasing the efficacy of antifolates which act via inhibition of dihydrofolate reductase (DHFR). The method comprises the steps of administration of 5-amino-4-imidazolecarboxamide riboside (Z) or its base with the antifolate such that the targeted cells are exposed to both the antifolate and Z simultaneously. This results in increased influx of the antifolate. For MTX, accumulation of the more biologically active polyglutamate forms is also potentiated. This potentiation appears to be mediated by an effect on the RFC.

  本发明提供了一种提高通过抑制二氢叶酸还原酶（DHFR）起作用的抗叶酸盐疗效的方法。该方法包括以下步骤：将 5-氨基-4-咪唑甲酰胺核苷（Z）或其碱基与抗叶酸盐一起给药，使靶细胞同时暴露于抗叶酸盐和 Z。这将增加抗叶酸的流入。对于 MTX 来说，生物活性更强的多谷氨酸形式的积累也会得到加强。这种增效作用似乎是由对 RFC 的影响介导的。
• Anti-tumor agents
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0239362B1

  公开（公告）日：1991-12-04