4-Amino-1-methyl-1H-imidazole-2-carboxylic acid [5-(3-dimethylamino-propylcarbamoyl)-1-methyl-1H-pyrrol-3-yl]-amide | 373362-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-Amino-1-methyl-1H-imidazole-2-carboxylic acid [5-(3-dimethylamino-propylcarbamoyl)-1-methyl-1H-pyrrol-3-yl]-amide
• 英文别名: 4-amino-N-[5-[3-(dimethylamino)propylcarbamoyl]-1-methylpyrrol-3-yl]-1-methylimidazole-2-carboxamide
• CAS: 373362-34-6
• 化学式: C₁₆H₂₅N₇O₂
• 分子量: 347.42
• InChiKey: RFXPWHGTZLFYCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-Amino-1-methyl-1H-imidazole-2-carboxylic acid [5-(3-dimethylamino-propylcarbamoyl)-1-methyl-1H-pyrrol-3-yl]-amide 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 、 N,N-二甲基甲酰胺 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 4-Amino-1-methyl-1H-imidazole-2-carboxylic acid [5-(3-dimethylamino-propylcarbamoyl)-1-methyl-1H-pyrrol-3-yl]-amide
  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
• Design, synthesis, and DNA binding characteristics of a group of orthogonally positioned diamino, N-formamido, pyrrole- and imidazole-containing polyamides
  作者：Sameer Chavda、Balaji Babu、Pravin Patil、Adam Plaunt、Amanda Ferguson、Megan Lee、Samuel Tzou、Robert Sjoholm、Toni Rice、Hilary Mackay、Joseph Ramos、Shuo Wang、Shicai Lin、Konstantinos Kiakos、W. David Wilson、John A. Hartley、Moses Lee

  DOI：10.1016/j.bmc.2013.04.001

  日期：2013.7

  solubility and enhanced binding affinity, whilst retaining DNA minor groove and sequence specificity compared to their monoamino/monocationic counterparts. The synthesis and DNA binding properties of the following diamino PAs: f-IPI (3a), f-IPP (4), f-PIP (5), and f-PPP (6) are described. P denotes the site where a 1-propylamino group is attached to the N1-position of the heterocycle. Binding of the diamino

  与单氨基/单阳离子对应物相比，正交定位的二氨基/双阳离子聚酰胺 (PA) 具有良好的水溶性和增强的结合亲和力，同时保留了 DNA 小沟和序列特异性。描述了以下二氨基 PA 的合成和 DNA 结合特性：fI P I ( 3a )、fI P P ( 4 )、f -P IP ( 5 ) 和 fP P P ( 6 )。磷表示1-丙基氨基连接到杂环的N1-位的位点。通过 DNase I 足迹、热变性、圆二色滴定、生物传感器表面等离子体共振 (SPR) 和等温滴定量热法 (ITC) 研究评估二氨基 PA 与 DNA 的结合。根据 SPR 研究，与单氨基类似物 f- 相比，fI P I ( 3a ) 结合更强烈 ( K eq  = 2.4 × 10 8  M -1 ) 并且与其同源序列 5'-ACGCGT-3' 具有相当的序列选择性IPI ( 1 )。fI P I ( 3a的结合) 到 5'-ACGCGT-3'
• Effects of N-terminus modified Hx-amides on DNA binding affinity, sequence specificity, cellular uptake, and gene expression
  作者：Konstantinos Kiakos、Vijay Satam、Pravin C. Patil、Jeffrey Sweers、Michael Bowerman、Sam Tzou、Kevin Olsen、Megan Lee、Helmut Schaschl、Bernhard K. Keppler、Daniel Hochhauser、Moses Lee、John A. Hartley、Luke Pett

  DOI：10.1016/j.bmcl.2021.128158

  日期：2021.9

  gene promoter, and inhibit protein complex binding. Interestingly, the 4-pyridyl analog 6a exhibits greater binding affinity for the target DNA sequence and abolishes the protein:ICB2 interaction in vitro, at a lower concentration, compared to the prototypical compound HxIP 3. Analogues 6b-e, display improved DNA sequence specificity, but reduced binding affinity for the cognate sequence, relative

  设计并合成了五个 X-HxIP（Hx-酰胺）6a-e，其中N端对茴香基部分进行了修饰，目的是优化 DNA 结合、提高细胞摄取/核渗透和增强对拓扑异构酶 IIα ( TOP2A ) 基因表达。修饰包括氟苯基和其他具有不同分子形状、大小和极性的杂环。像他们的母体化合物HxIP 3，所有五个X HxIP类似物优先结合到它们的同源序列5'-TACGAT-3'，其被发现嵌入在5'侧翼反转CCAAT盒-2（ICB2）站点中TOP2A基因启动子，并抑制蛋白质复合物结合。有趣的是，与原型化合物 HxIP 3相比，4-吡啶基类似物6a对目标 DNA 序列表现出更大的结合亲和力，并在体外以较低的浓度消除蛋白质：ICB2 相互作用。与未修饰的 HxIP 3 相比，类似物6b-e显示出改进的 DNA 序列特异性，但降低了对同源序列的结合亲和力，其中聚酰胺6b和6e是最具序列选择性的。然而，与3和6b不同，6a无法
• 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.