Benzyl 4-[[(4-Amino-1-methylpyrrol-2-yl)carbonyl]amino]-1-methylpyrrole-2-carboxylate | 77716-19-9

• 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: Benzyl 4-[[(4-Amino-1-methylpyrrol-2-yl)carbonyl]amino]-1-methylpyrrole-2-carboxylate
• 英文别名: Benzyl 4-<<(4-Amino-1-methylpyrrol-2-yl)carbonyl>amino>-1-methylpyrrole-2-carboxylate
• CAS: 77716-19-9
• 化学式: C₁₉H₂₀N₄O₃
• 分子量: 352.393
• InChiKey: BBVXJQFRGXTTHB-UHFFFAOYSA-N

物化性质

• 沸点：
  522.8±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  91.28
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  Benzyl 4-[[(4-Amino-1-methylpyrrol-2-yl)carbonyl]amino]-1-methylpyrrole-2-carboxylate 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 40.0 ℃ 、413.69 kPa 条件下， 反应 6.0h， 生成 1-Homodistamycin A
  参考文献：
  名称：

  Synthesis and antiviral activity of distamycin A analogs: substitutions on the different pyrrole nitrogens and in the amidine function

  摘要：

  Several new analogues of the antiviral antibiotic distamycin A were synthesized and assayed for their effects on influenza and herpes simplex virus. The new compounds 5b-j (R1-3 = H, CH3, and C2H5, R4,5 = H and CH3) were obtained via stepwise prepared formylated trimeric benzyl 4-aminopyrrole-2-carboxylates 3a-h, which after catalytic hydrogenolysis were coupled as N-succinimidyl esters directly with the proper beta-aminopropionamidine, unsubstituted or substituted with one or two methyl groups in the amidine function. Most of the new analogues did not exhibit significant effects on the viruses studied, but three compounds (5f-h) displayed activity on herpes virus as demonstrated in plaque formation and virus yield assays. Elevated cytotoxicity was simultaneously observed for 5g and 5h. For compound 5f, a partial separation of antiherpes activity and cytotoxicity was accomplished. The differences in antiherpes activity did not correspond to the differences in the inhibition of herpes virus DNA polymerase.

  DOI：

  10.1021/jm00361a018
• 作为产物：
  描述：

  Benzyl 4-Amino-1-methylpyrrole-2-carboxylate 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 Benzyl 4-[[(4-Amino-1-methylpyrrol-2-yl)carbonyl]amino]-1-methylpyrrole-2-carboxylate
  参考文献：
  名称：

  设计，合成，DNA结合和一系列DNA小沟结合插层药物的生物活性。

  摘要：

  合成了一组假肽，天然抗肿瘤剂双歧霉素或netropsin与苯胺基r啶发色团（与合成的抗白血病药物氨茶碱有关）的分子组合。确定并讨论了它们的DNA结合特性，并讨论了它们的结构差异以及与观察到的碱基依赖性结合。结合数据与模型一致，在模型中the啶核占据一个插入位点，而netropsin或distamycin残基位于DNA小沟中。报道了针对鼠细胞系的细胞抑制活性和细胞毒性活性，以及​​对DNA合成的抑制作用的显着差异。

  DOI：

  10.1002/jps.2600781106

文献信息

• Synthesis and evaluation of a netropsin–proximicin-hybrid library for DNA binding and cytotoxicity
  作者：Falko E. Wolter、Lise Molinari、Elke R. Socher、Kathrin Schneider、Graeme Nicholson、Winfried Beil、Oliver Seitz、Roderich D. Süssmuth

  DOI：10.1016/j.bmcl.2009.04.042

  日期：2009.7

  furan amino acid as a core structure. They show a moderate cytotoxic activity and induce upregulation of cell cycle regulating proteins (p53 and p21) and lead to cell cycle arrest in G0/G1-phase. Hybrid molecules combining structural motifs of the proximicins and of netropsin (4), a structurally related natural product, seem to have similar effects. Herein we describe the synthesis of a netropsin–proximicin-hybrid

  所述proximicins A-C（1 - 3）是新的天然存在的γ-肽具有迄今未知的2,4-二取代的呋喃氨基酸作为核心的结构。它们显示出中等的细胞毒活性，并诱导细胞周期调节蛋白（p53和p21）的上调，并导致细胞周期停滞在G0 / G1期。结合proximicin和netropsin（4）（一种与结构相关的天然产物）的结构基序的杂合分子似乎具有相似的作用。在这里，我们描述了netropsin-proximicin杂交文库的合成及其对细胞毒性和小沟结合活性的评估。
• Novel heterocyclic Tröger's base derivatives containing N-methylpyrrole units
  作者：Martin Valı&#x;k、Bohumil Dolensky、Hana Petřı&#x;čková、Petr Vašek、Vladimı&#x;r Král

  DOI：10.1016/s0040-4039(03)00177-1

  日期：2003.3

  preparation of Tröger's base derivatives of natural antibiotics via an amide protocol. The novel heterocyclic Tröger's bases were characterized by a variety of spectroscopic techniques and compound 2b by X-ray crystallography. Incorporation of guanidine as the terminal group in the N-methylpyrrole Tröger's base skeleton opens the possibility for preparation of water soluble derivatives.

  从4-氨基-N-甲基吡咯羧酸盐区域选择性地制备Tröger碱的新型类似物，收率很高。二苄基-4,9-甲醇-1,6-二甲基-4,5,9,10-四氢-1 H，6 H-二吡咯并-[3,2- b：3'，2'- f ]的催化加氢[1,5]二唑-2,7-二羧酸盐2b导致4,9-甲醇-1,6-二甲基-4,5,9,10-四氢-1 H，6 H-二吡咯并-[3,2- b：3'，2'- f ] [1,5]二唑-2,7-二羧酸3它通过酰胺方案用于制备Tröger天然抗生素的基础衍生物。通过多种光谱技术和化合物2b通过X射线晶体学表征了新型的Tröger杂环碱基。在N-甲基吡咯Tröger的基本骨架中引入胍作为末端基团，为制备水溶性衍生物提供了可能。
• Synthesis and Antiviral Activity of Three Pyrazole Analogues of Distamycin A.
  作者：Lu Ding、Leif Grehn、Erik De Clercq、Graciela Andrei、Robert Snoeck、Jan Balzarini、Bengt Fransson、Ulf Ragnarsson、George W. Francis

  DOI：10.3891/acta.chem.scand.48-0498

  日期：——

  The synthesis of three new monopyrazole analogues of the antiviral compound distamycin A is reported. Suitably protected 4-amino-1-methylpyrrole-2-carboxylic acid and 3-amino-1-methylpyrazole-5-carboxylic acid derivatives were chosen as starting materials. The construction of the trimeric polyamide framework was accomplished by assembly of the monomeric precursors under condensing conditions by analogy with our previous methodology, although with significant improvements in some pivotal steps. After chromatographic purification and spectroscopic characterisation, the analogues were assayed for antiviral activity. Compounds 7a-c inhibited vaccinia virus at a concentration similar to or lower than distamycin A and the related antibiotic netropsin. Analogues 7b and 7c exhibited an antiviral effect comparable to those of distamycin A and netropsin against HSV-1 and HSV-2, whereas their antiviral activity against several other viruses including HIV-1 and HIV-2 was somewhat lower. The cellular toxicity of 7a-c toward different host cell types proved to be of similar magnitude or lower than those of distamycin A and netropsin.
• Nishiwaki, Eiji; Nakagawa, Hirofumi; Takasaki, Michika, Heterocycles, 1990, vol. 31, # 10, p. 1763 - 1767
  作者：Nishiwaki, Eiji、Nakagawa, Hirofumi、Takasaki, Michika、Matsumoto, Toyomi、Sakurai, Hiromu、Shibuya, Masayuki

  DOI：——

  日期：——
• Novel efficient total synthesis of antiviral antibiotic distamycin A
  作者：Leif Grehn、Ulf Ragnarsson

  DOI：10.1021/jo00330a022

  日期：1981.8