4-(N-[2,4-二氨基-6-喋啶甲基]-氨基)苯酸钠盐 | 36093-85-3

• 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
• 中文名称: 4-(N-[2,4-二氨基-6-喋啶甲基]-氨基)苯酸钠盐
• 中文别名: 4-(N-[2,4-二氨基-6-喋啶甲基]-氨基)苯甲酸
• 英文名称: des-glu-aminopterin
• 英文别名: 4-[(2-amino-4-imino-3,4-dihydro-pteridin-6-yl-methyl)-amino]-benzoic acid；4-(N-((2,4-Diamino-6-pteridinyl)methyl)amino)benzoic acid；4-[(2,4-diaminopteridin-6-yl)methylamino]benzoic acid
• CAS: 36093-85-3
• 化学式: C₁₄H₁₃N₇O₂
• 分子量: 311.303
• InChiKey: OSYSFOFKQDNPGP-UHFFFAOYSA-N

物化性质

• 熔点：
  >226°C (dec.)
• 溶解度：
  DMSO（微溶，加热）、Methaol（微溶，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  9

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R20/21/22
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-(N-[2,4-二氨基-6-喋啶甲基]-氨基)苯酸钠盐 在 次氯酸叔丁酯 作用下， 以 三氟乙酸 为溶剂， 反应 2.0h， 生成 3,5-Dichloro-4-[(2,4-diaminopteridin-6-yl)methylamino]benzoic acid
  参考文献：
  名称：

  氨基蝶呤和3'，5-二氯氨基蝶呤的Nω-半邻苯二甲酰基-α，ω-二氨基链烷酸类似物的合成和生物活性。

  摘要：

  Nα-（4-氨基-4-脱氧蝶酰基）-Nδ-（半邻苯二甲酰基）-L-鸟氨酸（PT523）的类似物，在对氨基苯甲酰基部分具有3'，5'-二氯取代，或具有一个或多个或多个合成了氨基酸部分中的CH2基团，并将其作为二氢叶酸还原酶（DHFR）活性和细胞生长的抑制剂进行了测试。用L-2,4-二氨基丁酸或L-赖氨酸替代PT523中的L-鸟氨酸不会降低与人重组DHFR的结合力，但会导致针对SCC25人和SCC VII鼠鳞状细胞癌以及针对MCF-7的活性丧失人类乳腺癌的文化。PT523的效力比甲氨蝶呤（MTX），氨基蝶呤（AMT）或曲美脲（TMQ）强几倍。3'，5'-二氯取代不会降低DHFR结合或细胞毒性。从2到PT523的新合成路线 研究了4-二氨基-6-（羟甲基）蝶啶和甲基Nα-（4-氨基苯甲酰基）-N-邻苯二甲酰基-L-鸟氨酸盐，但没有发现其优于前述方法。在有关PT523和MTX竞争性抑制（6R）-5

  DOI：

  10.1021/jm00040a008
• 作为产物：
  描述：

  氨基蝶呤 在 sodium hydroxide 、 sodium acetate 、 溶剂黄146 、 zinc(II) chloride 作用下， 反应 24.0h， 以86%的产率得到4-(N-[2,4-二氨基-6-喋啶甲基]-氨基)苯酸钠盐
  参考文献：
  名称：

  Methotrexate analogs. 19. Replacement of the glutamate side-chain in classical antifolates by L-homocysteic acid and L-cysteic acid: effect on enzyme inhibition and antitumor activity

  摘要：

  Methotrexate (MTX) and aminopterin (AMT) analogues containing L-homocysteic acid or L-cysteic acid in place of L-glutamic acid were synthesized and tested as inhibitors of dihydrofolate reductase from L1210 cells and folyl polyglutamate synthetase from mouse liver. The ID50 against dihydrofolate reductase was comparable for the MTX and AMT analogues (0.04-0.07 microM), whereas the ID50 against folyl polyglutamate synthetase was 3- to 4-fold lower for the AMT analogues (40-60 microM) than for the MTX analogues (100-200 microM). Thus, N10-substitution has a greater effect on binding to folyl polyglutamate synthetase than dihydrofolate reductase. The cytotoxicity of these compounds was assayed in vitro against L1210 cells, and the AMT analogues again proved more potent (ID50 = 0.03-0.05 microM) than the MTX analogues (ID50 = 0.1-0.4 microM). A similarly increased potency was observed for the AMT analogues against L1210 leukemia in vivo. Though differential cell uptake cannot be ruled out as the basis of increased potency, it is possible that part of the activity of the AMT analogues involves interference with the intracellular polyglutamation of reduced folate cofactors, i.e., that they are "self-potentiating antifolates". Of the four compounds reported, the most active was N-(4-amino-4- deoxypteroyl )-L-homocysteic acid, which produced a 138% increase in life span (ILS) in L1210 leukemic mice when given on a modified bid X 10 schedule at a dose of 2 mg/kg. A comparable ILS was obtained with AMT itself at 0.24 mg/kg. Thus, replacement of gamma-CO2H by gamma-SO3H in the side chain does not decrease therapeutic effect. However, a higher dose is required, presumably to offset pharmacological differences reflecting the inability of the sulfonate group to be polyglutamated .

  DOI：

  10.1021/jm00371a008

文献信息

• Pharmaceutically active ornithine derivatives, ammonium salts thereof and methods of making same
  申请人：——

  公开号：US20040072837A1

  公开（公告）日：2004-04-15

  The present invention relates to pharmaceutically active ornithine compounds, particularly to pharmaceutically acceptable ammonium salts of N &dgr; -acyl derivatives of N &agr; (4-amino-4-deoxypteroyl)-L-omithine compounds; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such ammonium salts. The ammonium salts provided by the invention exhibit superior chemical stability than corresponding acidic N &dgr; -acyl derivatives of N &dgr; -acyl derivatives of N &agr; (4-amino-4-deoxypteroyl)-L-ornithine compounds.

  本发明涉及药用活性鸟氨酸化合物，特别是药用可接受的N &dgr; -酰基衍生物的铵盐，以及利用或包含这类铵盐的治疗方法和药物组合物。本发明提供的铵盐比相应的N &dgr; -酰基衍生物表现出更优越的化学稳定性，后者是N &agr; (4-氨基-4-脱氧叶酸)-L-鸟氨酸化合物的酸性N &dgr; -酰基衍生物。
• Methods of treating inflammatory diseases with ammonium salts of ornitihine derivatives
  申请人：Rosenwald A. Lindsay

  公开号：US20050032807A1

  公开（公告）日：2005-02-10

  The present invention relates to pharmaceutically active ornithine compounds, particularly to pharmaceutically acceptable ammonium salts of N δ -acyl derivatives of N α (4-amino-4-deoxypteroyl)-L-ornithine compounds; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such ammonium salts. The ammonium salts provided by the invention exhibit superior chemical stability than corresponding acidic N δ -acyl derivatives of N δ -acyl derivatives of N α (4-amino-4-deoxypteroyl)-L-ornithine compounds.

  本发明涉及药用活性鸟氨酸化合物，特别是药用可接受的Nδ-酰基衍生物的Nα(4-氨基-4-脱氧叶酸)-L-鸟氨酸化合物的铵盐；以及利用或包含其中一种或多种这种铵盐的治疗方法和药物组合物。本发明提供的铵盐比相应的Nδ-酰基衍生物的Nδ-酰基衍生物的Nα(4-氨基-4-脱氧叶酸)-L-鸟氨酸化合物表现出更优越的化学稳定性。
• Folate receptor binding conjugates of antifolates
  申请人：Leamon Christopher Paul

  公开号：US09192682B2

  公开（公告）日：2015-11-24

  Conjugates of antifolates, releasable linkers, and drugs, and pharmaceutical compositions containing them are described. The conjugates are useful for treating diseases arising from pathogenic cell populations. Methods for treating such diseases are also described.

  本文描述了抗叶酸类化合物、可释放连接剂和药物的共轭物，以及含有它们的制药组合物。这些共轭物对于治疗源于病原细胞群的疾病是有用的。本文还描述了治疗这种疾病的方法。
• Bioluminescent Antibodies for Point-of-Care Diagnostics
  作者：Lin Xue、Qiuliyang Yu、Rudolf Griss、Alberto Schena、Kai Johnsson

  DOI：10.1002/anie.201702403

  日期：2017.6.12

  We introduce a general method to transform antibodies into ratiometric, bioluminescent sensor proteins for the no-wash quantification of analytes. Our approach is based on the genetic fusion of antibody fragments to NanoLuc luciferase and SNAP-tag, the latter being labeled with a synthetic fluorescent competitor of the antigen. Binding of the antigen, here synthetic drugs, by the sensor displaces the

  我们介绍了一种通用方法，可将抗体转化为比例式生物发光传感器蛋白，以免洗分析物。我们的方法基于抗体片段与NanoLuc荧光素酶和SNAP标签的遗传融合，后者被抗原的合成荧光竞争剂标记。传感器与抗原（此处为合成药物）的结合使抗体的束缚荧光竞争剂发生位移，并破坏了荧光素酶与荧光团之间的生物发光共振能量转移（BRET）。半合成传感器显示出可调的响应范围（亚微摩尔至亚毫摩尔）和大的动态范围（ΔRmax> 500％），它们通过将样品点在纸上，然后用数码相机进行分析，可以对分析物进行定量。
• [EN] VITAMIN RECEPTOR DRUG DELIVERY CONJUGATES FOR TREATING INFLAMMATION<br/>[FR] CONJUGUÉS DE RÉCEPTEURS DE VITAMINE POUR ADMINISTRATION PHARMACOLOGIQUE UTILISÉS DANS LE TRAITEMENT DE L'INFLAMMATION
  申请人：ENDOCYTE INC

  公开号：WO2011079227A1

  公开（公告）日：2011-06-30

  Described herein are compositions, methods, compounds, conjugates, and kits for use in targeted drug delivery using drug delivery conjugates containing hydrophilic spacer linkers for use in treating disease states caused by pathogenic cell populations, such as inflammatory cells.

  本文描述了用于靶向药物传递的组合物、方法、化合物、共轭物和试剂盒，其中包含亲水性间隔连接物的药物传递共轭物，用于治疗由病原细胞群体（如炎性细胞）引起的疾病状态。