1-methyl-4-(1-methyl-1H-imidazole-2-carboxamido)-1H-pyrrole-2-carboxylic acid | 865307-73-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 1-methyl-4-(1-methyl-1H-imidazole-2-carboxamido)-1H-pyrrole-2-carboxylic acid
• 英文别名: 1-methyl-4-(1-methylimidazole-2-carboxamido)pyrrole-2-carboxylic acid；4-(1-methylimidazole-2-carboxamido)-1-methylpyrrole-2-carboxylic acid；1-methyl-4-(1-methylimidazole-2-amido)pyrrole-2-carboxylic acid；1-methyl-4-{[(1-methyl-1H-imidazol-2-yl)carbonyl]amino}-1H-pyrrole-2-carboxylic acid；1-Methyl-4-[(1-methyl-1H-imidazole-2-carbonyl)-amino]-1H-pyrrole-2-carboxylic acid；1-methyl-4-[(1-methylimidazole-2-carbonyl)amino]pyrrole-2-carboxylic acid
• CAS: 865307-73-9
• 化学式: C₁₁H₁₂N₄O₃
• 分子量: 248.241
• InChiKey: UUENVTHPJIDBSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  89.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-methyl-4-(1-methyl-1H-imidazole-2-carboxamido)-1H-pyrrole-2-carboxylic acid 在 4-二甲氨基吡啶 、 sodium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 sodium 1-methyl-4-{4-(1-methylimidazole-2-carboxamido)-1-methylpyrrole-2-carboxamido}imidazole-2-carboxylate
  参考文献：
  名称：

  Use of Ferrocene Scaffolds as Pendant Groups in Hairpin-Type Pyrrole-Imidazole Polyamide Molecules Showing Sequence-Selective Binding to DNA Duplexes

  摘要：

  The synthesis and properties of new cotljugate molecules, Fc-PIA, composed of ferrocene (Fc) and pyrrole-imidazole polyamides (PIA) are reported. As a PIA sequence, we chose Im-Py-Im/Py-Im-Py considering its future application to the SNPs detection of genes having a GCG/CGC sequence. Two types of Fc-containing linkers, i.e., ferrocene-1,1'-dicarboxamide and ferrocenecarboxamide, were designed, and several Fc-PIPA molecules having these linkers were synthesized. Titration studies by use of circular dichroism revealed that the carboxamide-type Fc-PIA could bind to the target DNA with an association constant of 10(7) M-1. In contrast, ferrocene dicarboxamide-type compounds have slightly weaker affinity for the target DNA. However, the affinity could be recovered by replacing one of the pyrrole residues with beta-alanine. We carried out the CV measurement and observed quasi-irreversible oxidation of the ferrocene moieties in the Fc-PIA compounds. These properties of Fc-PIA indicate the potential usefulness of these molecules in electrochemical detection of genes.

  DOI：

  10.1021/jo051247n
• 作为产物：
  描述：

  1-甲基-1H-咪唑-2-羧酸 在 甲醇 、 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 1-methyl-4-(1-methyl-1H-imidazole-2-carboxamido)-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  [EN] METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  [FR] PROCÉDÉS ET COMPOSÉS POUR LE TRAITEMENT D'UNE MALADIE GÉNÉTIQUE

  摘要：

  本公开涉及化合物和方法，用于调节dmpk的表达，并治疗dmpk发挥积极作用的疾病和病况。该化合物可以是一种转录调节分子，具有第一末端、第二末端和寡聚骨架，其中：a）第一末端包括一种DNA结合基团，能够非共价结合到核苷酸重复序列CAG或CTG；b）第二末端包括结合到调节分子的蛋白结合基团，该调节分子调节包含核苷酸重复序列CAG或CTG的基因的表达；c）寡聚骨架包括连接第一末端和第二末端的连接物。

  公开号：

  WO2021158707A1

文献信息

• 4-Methyltrityl-Protected Pyrrole and Imidazole Building Blocks for Solid Phase Synthesis of DNA-Binding Polyamides
  作者：Benedikt Heinrich、Olalla Vázquez

  DOI：10.1021/acs.orglett.9b04288

  日期：2020.1.17

  DNA-binding polyamides are synthetic oligomers of pyrrole/imidazole units with high specificity and affinity for double-stranded DNA. To increase their synthetic diversity, we report a mild methodology based on 4-methyltrityl (Mtt) solid phase peptide synthesis (SPPS), whose building blocks are more accessible than the standard Fmoc and Boc SPPS ones. We demonstrate the robustness of the approach by

  结合DNA的聚酰胺是吡咯/咪唑单元的合成低聚物，对双链DNA具有高特异性和亲和力。为了增加它们的合成多样性，我们报告了一种基于4-甲基三苯甲基（Mtt）固相肽合成（SPPS）的温和方法，该方法的构建基比标准Fmoc和Boc SPPS更为容易。我们通过准备和研究带有所有前体的发夹来证明该方法的鲁棒性。重要的是，我们的策略是正交的并且与敏感分子兼容，并且可以很容易地实现自动化。
• Facile Dimer Synthesis for DNA-Binding Polyamide Ligands
  作者：Modi Wetzler、David E. Wemmer

  DOI：10.1021/ol1013262

  日期：2010.8.6

  Pyrrole-imidazole polyamide ligands are highly sequence specific synthetic DNA-binding ligands that bind with high affinity. To counter the synthetic difficulties associated with coupling the electron-rich heterocyclic acids to the electron-deficient nucleophilic imidazole amine, a novel approach is described for synthesis of Fmoc-protected dimers for solid-phase peptide synthesis (SPPS). This method produces

  吡咯-咪唑聚酰胺配体是具有高亲和力的高度序列特异性合成DNA结合配体。为了解决与将富电子杂环酸偶联至缺电子亲核咪唑胺相关的合成难题，描述了一种用于固相肽合成（SPPS）的Fmoc保护的二聚体合成新方法。该方法以高收率生产二聚体，广泛适用于其他含杂环的聚酰胺，并提高了配体收率和合成时间。
• DNA Interstrand Crosslinks by H-pin Polyamide (<i>S</i> )<i>-seco</i> -CBI Conjugates
  作者：Chuanxin Guo、Sefan Asamitsu、Gengo Kashiwazaki、Shinsuke Sato、Toshikazu Bando、Hiroshi Sugiyama

  DOI：10.1002/cbic.201600425

  日期：2017.1.17

  Conjugates and crosslinks: H‐pin imidazole‐pyrrole polyamide seco‐CBI conjugates that can be used to form sequence‐specific DNA interstrand crosslinks (ICLs) have been synthesized. One conjugate, which contained a chiral (S)‐seco‐CBI moiety, exhibited the highest sequence‐specific ICL activity toward the target DNA sequence and was cytotoxic to a cancer cell line.

  缀合物和交联：已合成了可用于形成序列特异性DNA链间交联（ICL）的H-pin咪唑-吡咯聚酰胺seco - CBI缀合物。一种包含手性（S）-seco- CBI部分的缀合物，对目标DNA序列表现出最高的序列特异性ICL活性，并对癌细胞系具有细胞毒性。
• Electrochemically active ligand for sequence-specific detection of double-stranded nucleic acid molecule
  申请人：Sekine Mitsuo

  公开号：US20070172826A1

  公开（公告）日：2007-07-26

  The purpose of the present invention is to provide a compound that specifically binds to the base sequence of a double-stranded nucleic acid molecule. The compound can reduce the electrochemical signal/noise ratio (S/N) in electrochemical detection, and as a result, the detection sensitivity (precision) will be greatly improved so as to enable the determination of an ultratrace amount of nucleic acid molecule. The present invention relates to a ferrocene compound represented by the following general formula (I): wherein “A” represents a divalent ferrocene-containing linker or ferrocene-1,1′-yl, R 2 represents a hydrogen atom or alkyl; “n” and “m” represent any natural numbers; and “V” and “X” represent the pyrrole-imidazole-polyamide (PIPA); to a ligand consisting of said ferrocene compound for sequence-specific detection of double-stranded nucleic acid molecules; to a method for electrochemical detection of double-stranded nucleic acid molecules 8 with the use of said ligand; and to an apparatus or device for the electrochemical detection with the use of said ligand.

  本发明的目的是提供一种能够特异性结合双链核酸分子碱基序列的化合物。该化合物可降低电化学检测中的信号/噪声比（S/N），从而大大提高检测灵敏度（精度），使得能够确定极微量的核酸分子。本发明涉及一种由下述通式（I）表示的二茂铁化合物：其中“A”表示含二茂铁的二价连接基或二茂铁-1,1'-基，R2表示氢原子或烷基；“n”和“m”表示任意自然数；“V”和“X”表示吡咯-咪唑-多肽（PIPA）；以及利用该化合物制备的配体，用于序列特异性检测双链核酸分子、利用该配体进行电化学检测双链核酸分子的方法，以及利用该配体进行电化学检测的装置或设备。
• [EN] METHODS AND COMPOUNDS FOR MODULATING MYOTONIC DYSTROPHY 1<br/>[FR] PROCÉDÉS ET COMPOSÉS POUR MODULER UNE DYSTROPHIE MYOTONIQUE DE TYPE 1
  申请人：DESIGN THERAPEUTICS INC

  公开号：WO2022126000A1

  公开（公告）日：2022-06-16

  The present disclosure relates to transcription modulator molecule compounds and methods for modulating the expression of dmpk, and treating diseases and conditions in which dmpk plays an active role. The transcription modulator comprising a) the first terminus comprising a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) a second terminus comprising a protein-binding moiety capable of binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) an oligomeric backbone comprising a linker between the first terminus and the second terminus.

  本公开涉及转录调节分子化合物和调节dmpk表达的方法，以及治疗dmpk发挥积极作用的疾病和病症的方法。所述转录调节剂包括a）第一端包括DNA结合基团，能够非共价地结合到核苷酸重复序列CAG或CTG上；b）第二端包括蛋白结合基团，能够结合到调节分子上，该调节分子调节包括核苷酸重复序列CAG或CTG的基因的表达；以及c）寡聚骨架，包括连接第一端和第二端的连接物。