4-甲酰胺基-1-甲基咪唑-2-羧酸 | 128293-68-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-甲酰胺基-1-甲基咪唑-2-羧酸
• 英文名称: 4-formylamino-1-methylimidazole-2-carboxylic acid
• 英文别名: 4-formamido-1-methylimidazole-2-carboxamide；4-Formamido-1-methyl-1H-imidazole-2-carboxylic acid；4-formamido-1-methylimidazole-2-carboxylic acid
• CAS: 128293-68-5
• 化学式: C₆H₇N₃O₃
• 分子量: 169.14
• InChiKey: OVFKMTVVSGRRCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  84.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  4-甲酰胺基-1-甲基咪唑-2-羧酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  新型交联双Lexitropsins的合成

  摘要：

  共价交联的双lexitropsins的合成14，15和16设计成结合在双螺旋DNA的小沟中的特异性核苷酸序列进行说明。

  DOI：

  10.1016/s0040-4039(00)78347-x
• 作为产物：
  描述：

  1-甲基-4-硝基-2-(三氟乙酰)-1H-咪唑 在 palladium on activated charcoal 正丁基锂 、 四丁基氟化铵 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-甲酰胺基-1-甲基咪唑-2-羧酸
  参考文献：
  名称：

  新型交联双Lexitropsins的合成

  摘要：

  共价交联的双lexitropsins的合成14，15和16设计成结合在双螺旋DNA的小沟中的特异性核苷酸序列进行说明。

  DOI：

  10.1016/s0040-4039(00)78347-x

文献信息

• A Convenient Synthesis of Cross-Linked Homodimeric BIS-Lexitropsins
  作者：Naim H. Al-Said、J. William Lown

  DOI：10.1080/00397919508012668

  日期：1995.4

  A general synthetic route to cross-linked homodimeric bis-lexitropsins connected through the nitrogens of the central pyrrole ring with polymethylene chains (19a-c, 20a and 21a) is described. These compounds were designed for efficient DNA minor groove binding
• Grehn, Leif; Ding, Lu; Ragnarsson, Ulf, Acta Chemica Scandinavica, 1990, vol. 44, # 1, p. 67 - 74
  作者：Grehn, Leif、Ding, Lu、Ragnarsson, Ulf

  DOI：——

  日期：——
• <i>N</i><b>‐Formamido‐Containing Mono‐ and Diheterocyclic Pyrrole‐and Imidazole‐2‐carboxylic Acids as Building Blocks for Polyamide Synthesis</b>
  作者：Keith Mulder、Jim Sexton、Zarmeen Taherbhai、Justin Jones、Peter Uthe、Toni Brown、Moses Lee

  DOI：10.1080/00397910701648785

  日期：2007.12.1

  Four N-formamido-containing mono-and diheterocyclic pyrrole- and imidazole-2-containing acids 1-4 were synthesized as intermediates for the preparation of polyamide molecules. The N-formamido-moiety forces the compounds to bind strongly as a stacked dimer, and in a staggered fashion, at specific sequences in the minor-groove of DNA. The acid moiety at the C-terminus of compounds enables these molecules to be coupled to amine-containing intermediates to form the amide linkages of the target polyamide. This convergent approach increases the synthetic diversity in polyamide chemistry by enabling one acid to be used with a variety of different C-terminus-functionalized intermediates.
• Synthesis and biophysical evaluation of minor-groove binding C-terminus modified pyrrole and imidazole triamide analogs of distamycin
  作者：Toni Brown、Zarmeen Taherbhai、Jim Sexton、Arden Sutterfield、Mark Turlington、Justin Jones、Lindsay Stallings、Michelle Stewart、Karen Buchmueller、Hilary Mackay

  DOI：10.1016/j.bmc.2006.09.037

  日期：2007.1.1

  Five polyamide derivatives with rationally modified C-terminus moieties were synthesized and their DNA binding specificity and affinity determined. A convergent approach was employed to synthesize polyamides containing an alkylaminopiperazine (4 and 5), a truncated piperazine (6), or an alkyldiamino-C-terminus moiety (7 and 8) with two specific objectives: to investigate the effects of number of potential cationic centers and steric bulk at the C-terminus. CD studies confirmed that compounds 4, 5, 7, and 8 bind in the minor groove of DNA. The alkylpiperazine containing compounds (4 and 5) showed only moderate binding to DNA with AT values of 2.8 and 8.3 degrees C with their cognate sequence, respectively. The alkyldiamino compounds (7 and 8) were more impressive producing a Delta T-m of > 17 and > 22 degrees C, respectively. Compound 6 (truncated piperazine) did not stabilize its cognate DNA sequence. Footprints were observed for all compounds (except compound 6) with their cognate DNA sequence using DNase I footprinting, with compound 7 producing a footprint of 0.1 mu M at the expected 5'-ACGCGT-3' site. SPR analysis of compound 7 bindiy to 5'-ACGCGT-3', 5'-ACCGGT-3', and 5'-AAATTT-3' produced binding affinities of 2.2 x 10(6), 3.3 x 10(5), and 1 x 10(5) M-1, respectively, indicating a preference for its cognate sequence of 5'-ACGCGT-3'. These results are in good agreement with the footprinting data. The results indicate that steric crowding at the C-terminus is important with respect to binding. However, the number of cationic centers within the molecule may also play a role. The alkyldiamino-containing compounds (7 and 8) warrant further investigation in the field of polyamide research. (c) 2006 Elsevier Ltd. All rights reserved.
• Sequence specific and high affinity recognition of 5′-ACGCGT-3′ by rationally designed pyrrole-imidazole H-pin polyamides: Thermodynamic and structural studies
  作者：Hilary Mackay、Toni Brown、Peter B. Uthe、Laura Westrate、Alan Sielaff、Justin Jones、James P. Lajiness、Jerome Kluza、Caroline O’Hare、Binh Nguyen、Zach Davis、Chrystal Bruce、W. David Wilson、John A. Hartley、Moses Lee

  DOI：10.1016/j.bmc.2008.09.034

  日期：2008.10

  Imidazole (Im) and Pyrrole (Py)-containing polyamides that can form stacked dimers can be programmed to target specific sequences in the minor groove of DNA and control gene expression. Even though various designs of polyamides have been thoroughly investigated for DNA sequence recognition, the use of H-pin polyamides (covalently cross-linked polyamides) has not received as much attention. Therefore, experiments were designed to systematically investigate the DNA recognition properties of two symmetrical H-pin polyamides composed of PyImPyIm (5) or f-ImPyIm (3e, f = formamido) tethered with an ethylene glycol linker. These compounds were created to recognize the cognate 5 '-ACGCGT-3 ' through an overlapped and staggered binding motif, respectively. Results from DNaseI footprinting, thermal denaturation, circular dichroism, surface plasmon resonance and isothermal titration microcalorimetry studies demonstrated that both H-pin polyamides bound with higher afinity than their respective monomers. The binding afinity of formamido-containing H-pin 3e was more than a hundred times greater than that for the tetraamide H-pin 5, demonstrating the importance of having a formamido group and the staggered motif in enhancing affinity. However, compared to H-pin 3e, tetraamide H-pin 5 demonstrated superior binding preference for the cognate sequence over its non-cognates, ACCGGT and AAATTT. Data from SPR experiments yielded binding constants of 1.6 x 10(8) M (1) and 2.0 x 10(10) M (1) for PyImPyIm H-pin 5 and f-ImPyIm H-pin 3e, respectively. Both H-pins bound with significantly higher affinity (ca. 100-fold) than their corresponding unlinked PyImPyIm 4 and f-ImPyIm 2 counterparts. ITC analyses revealed modest enthalpies of reactions at 298 K (Delta H of -3.3 and -1.0 kcal mol (1) for 5 and 3e, respectively), indicating these were entropic-driven interactions. The heat capacities (Delta C(p)) were determined to be -116 and -499 cal mol (1) K (1), respectively. These results are in general agreement with Delta C(p) values determined from changes in the solvent accessible surface areas using complexes of the H-pins bound to (5 ' CCACGCGTGG)(2) . According to the models, the H-pins fit snugly in the minor groove and the linker comfortably holds both polyamide portions in place, with the oxygen atoms pointing into the solvent. In summary, the H-pin polyamide provides an important molecular design motif for the discovery of future generations of programmable small molecules capable of binding to target DNA sequences with high affinity and selectivity. 2008 Elsevier Ltd. All rights reserved.