1-methyl-4-(1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylic acid | 67974-03-2

• 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
• 英文名称: 1-methyl-4-(1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylic acid
• 英文别名: 1-methyl-4-[1-methyl-4-(1-methyl-4-nitro-pyrrole-2-carbonylamino)-pyrrole-2-carbonylamino]-pyrrole-2-carboxylic acid；1-methyl-4-[1-methyl-4-[1-methyl-4-nitropyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxylic acid；1-methyl-4-[[1-methyl-4-[(1-methyl-4-nitropyrrole-2-carbonyl)amino]pyrrole-2-carbonyl]amino]pyrrole-2-carboxylic acid
• CAS: 67974-03-2
• 化学式: C₁₈H₁₈N₆O₆
• 分子量: 414.378
• InChiKey: QGBSUPQOOBPONH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-methyl-4-(1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylic acid 在 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、137.9 kPa 条件下， 反应 0.83h， 生成 4-(4-(4-formamido-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  [EN] DNA BINDING AGENTS WITH A MINOR GROOVE BINDING TAIL
  [FR] AGENTS LIANT L'ADN AVEC UNE QUEUE SE LIANT AU SILLON MINEUR

  摘要：

  本文提供的是一些能够插入细胞DNA并能够穿过血脑屏障的化合物。此外，本文还提供了这些化合物的药物组合物以及治疗癌症的方法，例如大脑、肺部或胰腺癌。

  公开号：

  WO2017049091A1
• 作为产物：
  描述：

  1-甲基-4-硝基吡咯-2-羧酸 生成 1-methyl-4-(1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  DNA亲和力裂解：Distamycin-EDTA-Fe（II）和EDTA-distamycin Fe（II）对DNA的序列特异性裂解

  摘要：

  的附接EDTA ·的Fe（II）到偏端霉素改变序列特异性DNA结合的抗生素为序列特异性DNA切割分子。我们报道了具有金属螯合剂EDTA的EDTA -distamycin（ED）的合成，该金属螯合剂被束缚在抗菌素distamycin的N-甲基吡咯三肽部分的羧基末端。EDTA -distamycin-的Fe（II）（ED）· FeII在10 -6 M个浓度有效地切割的pBR322 DNA（10 -5 M在碱基对）在氧和二硫苏糖醇的存在下（DTT）。使用Maxam-Gilbert测序凝胶分析，我们发现ED ·Fe（II）提供了不等强度的DNA裂解模式，覆盖了由腺嘌呤（A）和胸腺嘧啶（T）组成的5个碱基对位点附近的2至4个连续碱基对。每个位点的多次裂解可能是一种可扩散的氧化物质（可能是羟基）的证据。在A + T位点的每一侧的不均等的切割强度允许指定三肽结合单位的主要和次要方向。ED ·Fe（II）与双歧霉素-EDTA

  DOI：

  10.1016/0040-4020(84)85050-4

文献信息

• A Bis(guanidinium)alcohol Attached to a Hairpin Polyamide: Synthesis, DNA Binding, and Plasmid Cleavage
  作者：Daniela Wirth-Hamdoune、Stefan Ullrich、Ute Scheffer、Toni Radanović、Gerd Dürner、Michael W. Göbel

  DOI：10.1002/cbic.201500566

  日期：2016.3.15

  phosphate diesters and to react by nucleophilic displacement has been attached to a DNA‐binding Dervan‐type hairpin polyamide. The resulting conjugate nicks plasmid DNA at concentrations ranging from micromolar to high nanomolar.

  刻薄！设计用于与磷酸二酯形成离子对络合物并通过亲核取代反应的阳离子醇已与结合DNA的Dervan型发夹式聚酰胺连接。所得的缀合物切口质粒DNA的浓度范围为微摩尔至高纳摩尔。
• Facile synthesis of novel fluorescent distamycin analogues
  作者：Santanu Bhattacharya、Mini Thomas

  DOI：10.1016/s0040-4039(01)01040-1

  日期：2001.8

  A facile synthesis of four distamycin analogues that bear the dansyl fluorophore is described. The nature of the linkage between the fluorophore and the sequence recognition element had a dramatic effect on the fluorescence properties of these ligands upon DNA binding.

  描述了一种带有丹磺酰基荧光团的四种间他霉素类似物的简便合成方法。荧光基团和序列识别元件之间的连接性质对DNA结合后的这些配体的荧光性质产生了显着影响。
• Acryloyl derivatives analogous to distamycin, process for preparing them, and their use as antitumor agents
  申请人：Pharmacia & Upjohn S.p.A.

  公开号：US06753316B1

  公开（公告）日：2004-06-22

  Compounds which are acryloyl substituted distamycin derivatives of formula (I) wherein: n is 2, 3 or 4; m is 1 or 2; X and Y are the same or different and are selected, independently for each heterocyclic ring of the polyetherocyclic chain, from N and CH; R1 and R2, which are the same or different, are selected from hydrogen, halogen, and C1-C4 alkyl; R3 is hydrogen or halogen; B is selected from (a), (b), (c), (d), (e), (f), (g) and —C≡N; wherein R4, R5, R6, R7, R8, R10, R11, and R12 are, independently from each other, hydrogen or C1-C4 alkyl; and R9 is hydrogen or hydroxy, or pharmaceutically acceptable salt thereof; provided that a) at least one of R4, R5 and R6 is alkyl b) at least one of the heterocyclic rings within the polyheterocyclic chain is other than pyrole; and c) X and Y are not both N for the same heterocyclic ring; are useful as antitumor agents.

  化合物是acryloyl取代的formula（I）的distamycin衍生物，其中：n为2、3或4；m为1或2；X和Y相同或不同，分别选自N和CH，为聚醚杂环链的每个杂环环；R1和R2相同或不同，选自氢、卤素和C1-C4烷基；R3为氢或卤素；B选自（a）、（b）、（c）、（d）、（e）、（f）、（g）和—C≡N；其中R4、R5、R6、R7、R8、R10、R11和R12独立地选自氢或C1-C4烷基；R9为氢或羟基，或其药用可接受的盐；条件是a）R4、R5和R6中至少有一个是烷基；b）聚杂环链内至少有一个杂环环不是吡咯；和c）X和Y对于相同的杂环环不同时为N；这些化合物可用作抗肿瘤剂。
• Acryloyl substituted distamycin derivatives, process for preparing them, and their use as antitumor and antiviral agents
  申请人：Pharmacia & Upjohn S.p.A.

  公开号：US20030023031A1

  公开（公告）日：2003-01-30

  According to the invention, there is provided a method of manufacturing a medicament for use in the treatment of cancer or viral infections which comprises obtaining a cancer treating effective amount of a compound of formula (I), 1 and combining the compound of formula (I) with at least one pharmaceutically acceptable excipient, and wherein the cancer treating effective amount of a compound of formula I is an acryloyl substituted distamycin derivative in which n, R 1 and R 2 , R 3 , B, are defined herein or a pharmaceutically acceptable salt thereof to produce a medicament for use in the treatment of cancer or viral infections.

  根据本发明，提供了一种制造治疗癌症或病毒感染的药物的方法，该方法包括获取公式（I）化合物的治疗癌症有效量，1并将公式（I）化合物与至少一种药用可接受的赋形剂结合，其中公式I化合物的治疗癌症有效量是一种丙烯酰基取代的二氨基链霉素衍生物，其中n，R1和R2，R3，B在此定义，或其药用可接受盐，以制备用于治疗癌症或病毒感染的药物。
• Benzoheterocyclic distamycin derivatives, process for preparing them, and their use as antitumor agents
  申请人：Pharmacia & Upjohn, S.p.A.

  公开号：US06458768B1

  公开（公告）日：2002-10-01

  Compounds which are benzoheterocyclic distamycin derivatives of formula (I), wherein n is 2, 3 or 4; A is a heteroatom selected from O and S or is a group NR, wherein R is hydrogen or C1-C4 alkyl; B is CH or N; R1 is hydrogen or C1-C4 alkyl; G is selected from the group consisting of (a, b, c, d, e, f, g, h, i, j), and —C≡N; wherein R5, R6, R7, R8, R9, R10, R11 and R12 are, independently from each other, hydrogen or C1-C4 alkyl; T is a group of formula (II) or (III) as defined above, wherein p is 0 or 1; R2 and R3 are, independently from each other, hydrogen, C1-C4 alkyl optionally substituted by one or more fluorine atoms, or C1-C4 alkoxy; R4 is C1-C4 alkyl or C1-C3 haloalkyl; X1 and X2 are halogen atoms or pharmaceutically acceptable salts thereof; provided that at least one of R5, R6 and R7 is alkyl; are useful as antitumor agents.

  式（I）的苯并杂环二聚霉素衍生物化合物，其中n为2、3或4；A为从O和S中选择的杂原子或为NR基团，其中R为氢或C1-C4烷基；B为CH或N；R1为氢或C1-C4烷基；G从（a，b，c，d，e，f，g，h，i，j）和—C≡N的群中选择；其中R5、R6、R7、R8、R9、R10、R11和R12各自独立地是氢或C1-C4烷基；T为如上所定义的式（II）或（III）的基团，其中p为0或1；R2和R3各自独立地是氢、C1-C4烷基，可选地取代一个或多个氟原子，或C1-C4烷氧基；R4为C1-C4烷基或C1-C3卤代烷基；X1和X2为卤素原子或其药学上可接受的盐；前提是R5、R6和R7中至少有一个为烷基；这些化合物作为抗肿瘤剂是有用的。