1H-咪唑-2-甲酰胺,N-[5-[[[3-(二甲氨基)丙基]氨基]羰基]-1-甲基-1H-吡咯-3-基]-1-甲基-4-[[(1-甲基-4-硝基-1H-吡咯-2-基)羰基]氨基]- | 163012-91-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1H-咪唑-2-甲酰胺,N-[5-[[[3-(二甲氨基)丙基]氨基]羰基]-1-甲基-1H-吡咯-3-基]-1-甲基-4-[[(1-甲基-4-硝基-1H-吡咯-2-基)羰基]氨基]-
• 英文名称: N-methyl-4-(N-methyl-4-(N-methyl-4-nitropyrrole-2-carboxamido)-imidazole-2-carboxamido)-2-(carboxamidopropyl-3-dimethylamino)pyrrole
• 英文别名: 1-methyl-4-{1-methyl-4-(1-methyl-4-nitropyrrole-2-carboxamido)imidazole-2-carboxamido}-2-(3-dimethyl(aminopropyl)aminocarbonyl)pyrrole；1-methyl-4-{1-methyl-4-(1-methyl-4-nitropyrole-2-carboxamido)imidazole-2-carboxamido}-2-(3-dimethylaminopropylaminocarbonyl)pyrrole；N-[5-[3-(dimethylamino)propylcarbamoyl]-1-methylpyrrol-3-yl]-1-methyl-4-[(1-methyl-4-nitropyrrole-2-carbonyl)amino]imidazole-2-carboxamide
• CAS: 163012-91-7
• 化学式: C₂₂H₂₉N₉O₅
• 分子量: 499.53
• InChiKey: AULGWQDFTKCWJZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  164
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1H-咪唑-2-甲酰胺,N-[5-[[[3-(二甲氨基)丙基]氨基]羰基]-1-甲基-1H-吡咯-3-基]-1-甲基-4-[[(1-甲基-4-硝基-1H-吡咯-2-基)羰基]氨基]- 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 tert-butyl N-[1-[[5-[[2-[[5-[3-(dimethylamino)propylcarbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-4-[[1-methyl-4-[[1-methyl-4-[(1-methylimidazole-2-carbonyl)amino]pyrrole-2-carbonyl]amino]imidazole-2-carbonyl]amino]-1-oxobutan-2-yl]carbamate
  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：

  N-[3-(dimethylamino)propyl]-1-methyl-4-nitro-1H-pyrrole-2-carboxamide 在 10% palladium on active carbon 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 1H-咪唑-2-甲酰胺,N-[5-[[[3-(二甲氨基)丙基]氨基]羰基]-1-甲基-1H-吡咯-3-基]-1-甲基-4-[[(1-甲基-4-硝基-1H-吡咯-2-基)羰基]氨基]-
  参考文献：
  名称：

  吡咯/咪唑 CPI 偶联物的高效序列特异性 DNA 链间交联

  摘要：

  我们通过合成吡咯 (Py)/咪唑 (Im)-二酰胺-CPI 偶联物 ImPyLDu86 (1) 的二聚体，使用七种不同的接头连接，开发了一种新型 DNA 链间交联剂。四亚甲基接头化合物 7b 仅在伴侣三酰胺 ImImPy 存在的情况下有效地在九个碱基对序列 5'-PyGGC(T/A)GCCPu-3' 处产生 DNA 链间交联。为了通过 7b 与 ImImPy 进行有效交联，需要两个识别位点之间的一个 AT 碱基对来容纳接头区域。消除 AT 碱基对和插入额外的 AT 碱基对并用 GC 碱基对替换显着降低了交联程度。在存在各种三酰胺的情况下，还检查了 7b 的链间交联的序列特异性。与 ImImPy 相比，ImImIm 的存在略微减少了交联产物的形成。错配伙伴 ImPyPy 和 PyImPy 不与 7b 产生链间交联产物，而 ImPyPy 和 PyImPy 在其与 7b 的匹配位点诱导有效烷基化。使用变性聚丙烯酰胺凝胶电泳和

  DOI：

  10.1021/ja028459b

文献信息

• Recognition in the Minor Groove of DNA at 5'-(A,T)GCGC(A,T)-3' by a Four Ring Tripeptide Dimer. Reversal of the Specificity of the Natural Product Distamycin
  作者：Milan Mrksich、Peter B. Dervan

  DOI：10.1021/ja00117a002

  日期：1995.3

  The tripeptide ImPImP containing alternating imidazole and pyrrole carboxamides specifically binds the designated six base pair site 5'-d(A,T)GCGC(A,T)-3' in the minor groove of DNA. Quantitative footprint titration experiments demonstrate that ImPImP binds the sites 5'-AGCGCT-3' and 5'-TGCGCA-3' with apparent first order binding affinities of 3.8 x 10^5 M^(-1) and 3.6 x 10^5 M^(-1), respectively (25

  含有交替咪唑和吡咯甲酰胺的三肽 ImPImP 特异性结合 DNA 小沟中指定的六碱基对位点 5'-d(A,T)GCGC(A,T)-3'。定量足迹滴定实验表明 ImPImP 以 3.8 x 10^5 M^(-1) 和 3.6 x 10^5 M 的明显一级结合亲和力结合位点 5'-AGCGCT-3' 和 5'-TGCGCA-3' ^(-1)，分别为（25 mM tris 醋酸盐，10 mM NaCl，pH 7.0 和 22 °C）。ImPImP-EDTA 的亲和裂解实验。Fe 显示 5'-(A,T)GCGC(A,T)-3' 位点两侧的切割相等，与小沟中四个环肽的并排反平行排列一致，这种逆转倾向于结合纯 A、T 序列的天然产物远霉素的特异性强调了 2 的效用：1 肽-DNA 模型，用于设计用于 DNA 小沟中序列特异性识别的配体。通过将这些肽扩展到四个环系统，定义了 2:1 肽-DNA 复合物结合
• 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。
• ELECTROCHEMICALLY ACTIVE LIGAND FOR SEQUENCE-SPECIFIC DETECTION OF DOUBLE-STRANDED NUCLEIC ACID MOLECULE
  申请人：Japan Science and Technology Agency

  公开号：EP1719777A1

  公开（公告）日：2006-11-08

  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, R2 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与双链核酸分子的碱基序列特异性结合的化合物。该化合物可以降低电化学检测中的电化学信噪比（S/N），从而大大提高检测灵敏度（精度），从而可以测定超微量的核酸分子。本发明涉及由以下通式（I）代表的二茂铁化合物： 其中 "A "代表含二茂铁的二价连接体或二茂铁-1，1'-基，R2代表氢原子或烷基；"n "和 "m "代表任何自然数；"V "和 "X "代表吡咯-咪唑-聚酰胺（PIPA）；由所述二茂铁化合物组成的用于序列特异性检测双链核酸分子的配体；使用所述配体对双链核酸分子进行电化学检测的方法；以及使用所述配体进行电化学检测的装置或设备。
• EP1719777
  申请人：——

  公开号：——

  公开（公告）日：——
• Hx, a Novel Fluorescent, Minor Groove and Sequence Specific Recognition Element: Design, Synthesis, and DNA Binding Properties of <i>p</i>-Anisylbenzimidazole-imidazole/pyrrole-Containing Polyamides
  作者：Sameer Chavda、Yang Liu、Balaji Babu、Ryan Davis、Alan Sielaff、Jennifer Ruprich、Laura Westrate、Christopher Tronrud、Amanda Ferguson、Andrew Franks、Samuel Tzou、Chandler Adkins、Toni Rice、Hilary Mackay、Jerome Kluza、Sharjeel A Tahir、Shicai Lin、Konstantinos Kiakos、Chrystal D. Bruce、W. David Wilson、John A. Hartley、Moses Lee

  DOI：10.1021/bi102028a

  日期：2011.4.19

  With the aim of incorporating a recognition element that acts as a fluorescent probe upon binding to DNA, three novel pyrrole (P) and imidazole (I)-containing polyamides were synthesized. The compounds contain a p-anisylbenzimidazolecarboxamido (Hx) moiety attached to a PP, IP, or PI unit, giving compounds HxPP (2), HxIP (3), and HxPI (4), respectively. These fluorescent hybrids were tested against their complementary nonfluorescent, non-formamido tetraamide counterparts, namely, PPPP (5), PPIP (6), and PPPI (7) (cognate sequences 5'-AAATTT-3', 5'-ATCGAT-3', and 5'-ACATGT-3', respectively). The binding affinities for both series of polyamides for their cognate and noncognate sequences were ascertained by surface plasmon resonance (SPR) studies, which revealed that the Fix-containing polyamides gave binding constants in the 10(6) M-1 range while little binding was observed for the noncognates. The binding data were further compared to the corresponding and previously reported formainido-triamides f-PPP (8), f-PIP (9), and f-PPI (10). DNase I footprinting studies provided additional evidence that the Fix moiety behaved similarly to two consecutive pyrroles (PP found in 5-7), which also behaved like a formamido-pyrrole (f-P) unit found in distamycin and many formamido-triamides, including 8-10. The biophysical characterization of polyamides 2-7 on their binding to the abovementioned DNA sequences was determined using thermal melts (Delta T-M), circular dichroism (CD), and isothermal titration calorimetry (ITC) studies. Density functional calculations (B3LYP) provided a theoretical framework that explains the similarity between PP and Hx on the basis of molecular electrostatic surfaces and dipole moments. Furthermore, emission studies on polyamides 2 and 3 showed that upon excitation at 322 nm binding to their respective cognate sequences resulted in an increase in fluorescence at 370 nm. These low molecular weight polyamides show promise for use as probes for monitoring DNA recognition processes in cells.