N-methyl-imidazole-2-carboxylic acid lithium salt | 684242-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-methyl-imidazole-2-carboxylic acid lithium salt
• 英文别名: lithium 1-methyl-1H-imidazole-2-carboxylate；1-Methylimidazole-2-carboxylic acid, lithium salt；lithium;1-methylimidazole-2-carboxylate
• CAS: 684242-85-1
• 化学式: C₅H₅N₂O₂*Li
• 分子量: 132.048
• InChiKey: VDDMYAZKEZRYKJ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.21
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  4-[(4-Amino-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-imidazole-2-carboxylic acid (2-dimethylamino-ethyl)-amide 、 N-methyl-imidazole-2-carboxylic acid lithium salt 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以28%的产率得到N-(2-(dimethylamino)ethyl)-1-methyl-4-(1-methyl-4-(1-methyl-1H-imidazole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-imidazole-2-carboxamide
  参考文献：
  名称：

  Modifying the N-terminus of polyamides: PyImPyIm has improved sequence specificity over f-ImPyIm

  摘要：

  Seven N-terminus modified derivatives of a previously published minor-groove binding polyamide (f-ImPyIm, 1) were synthesized and the biochemical and biophysical chemistry evaluated. These compounds were synthesized with the aim of attaining a higher level of sequence selectivity over f-ImPyIm (1), a previously published strong minor-groove binder. Two compounds possessing a furan or a benzofuran moiety at the N-terminus showed a footprint of 0.5 mu M at the cognate ACGCGT site (determined by DNase I footprinting); however, the specificity of these compounds was not improved. In contrast, PyImPyIm (4) produced a footprint of 0.5 mu M but showed a superior specificity using the same technique. When evaluated by thermal melting experiments and circular dichroism using ACGCGT and the non-cognate AAATTT sequence, all compounds were shown to bind in the minor-groove of DNA and stabilize the cognate sequence much better than the non-cognate (except for the non-amido-compound that did not bind either sequence, as expected). PyImPyIm (4) was interesting as the Delta T(m) for this compound was only 4 degrees C but the footprint was very selective. No binding was observed for this compound with a third DNA (non-cognate, ACCGGT). ITC studies on compound 4 showed exothermic binding with ACGCGT and no heat change was observed for titrating the compound to the other two DNA sequences. The heat capacity (Delta C(p)) of the PIPI/ACGCGT complex calculated from the hydrophobic interactions and SASA calculations was comparable to the experimental value obtained from ITC (-146 cal mol(-1) K(-1)). SPR results provided con. firmation of the sequence specificity of PyImPyIm (4), with a K(eq) value determined to be 7.1 x 10(6) M(-1) for the cognate sequence and no observable binding to AAATTT and ACCGGT. Molecular dynamic simulations affirmed that PyImPyIm (4) binds as a dimer in an overlapped conformation, and it fits snugly in the minor-groove of the ACGCGT oligonucleotide. PyImPyIm (4) is an especially interesting molecule, because although the binding affinity is slightly reduced, the specificity with respect to f-ImPyIm (1) is significantly improved. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.03.008

文献信息

• [EN] COMPOUNDS THAT INTERACT WITH THE RAS SUPERFAMILY FOR THE TREATMENT OF CANCERS, INFLAMMATORY DISEASES, RASOPATHIES, AND FIBROTIC DISEASE<br/>[FR] COMPOSÉS INTERAGISSANT AVEC LA SUPERFAMILLE RAS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE CANCERS, DE MALADIES INFLAMMATOIRES, DE RASOPATHIES ET DE MALADIES FIBROTIQUES
  申请人：SHY THERAPEUTICS LLC

  公开号：WO2018237084A1

  公开（公告）日：2018-12-27

  Provided herein are methods and compositions for treating cancers, inflammatory diseases, rasopathies, and fibrotic disease involving aberrant Ras superfamily signaling through the binding of compounds to the GTP binding domain of Ras superfamily proteins including, in certain cases, K-Ras and mutants thereof, and a novel method for assaying such compositions.

  本发明提供了治疗癌症、炎症性疾病、rasopathy症和涉及异常Ras超家族信号传导的纤维化疾病的方法和组合物，这些方法和组合物通过化合物与Ras超家族蛋白（包括在某些情况下K-Ras及其突变体）的GTP结合域的结合来实现。此外，还提供了一种用于检测这些组合物的新方法。
• U-Pin Polyamide Motif for Recognition of the DNA Minor Groove
  作者：Alexander Heckel、Peter B. Dervan

  DOI：10.1002/chem.200304784

  日期：2003.7.21

  DNA-binding hairpin pyrrole-imidazole polyamides with gamma-aminobutyric acid as a turn-forming residue tolerate A.T or T.A base pairs under the turn. U-pins-polyamides with a different turn-have been synthesized and their DNA binding properties were studied. The two turn-forming residues are connected via the ring nitrogens using variable length aliphatic linkers ((CH(2))(n), n=3-6). Through optimization

  DNA结合的发夹式吡咯-咪唑聚酰胺，具有γ-氨基丁酸作为回旋形成残基，可在回旋下耐受AT或TA碱基对。已经合成了具有不同转角的U-pins-聚酰胺，并研究了它们的DNA结合特性。使用可变长度的脂族接头（（CH（2））（n），n = 3-6）经由环氮连接两个形成环的残基。通过优化接头长度和U形转角上吡咯残基2-位的取代基，可以发现具有GC / CG耐受性转角的聚酰胺，该聚酰胺以可预测的方式与DNA结合。