tert-butyl 2-{[(1-methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-1H-pyrrol-2-yl)carbonyl]amino}ethylcarbamate | 197705-42-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 2-{[(1-methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-1H-pyrrol-2-yl)carbonyl]amino}ethylcarbamate
• 英文别名: [2-({1-methyl-4-[(1-methyl-4-nitro-1H-pyrrole-2-carbonyl)-amino]-1H-pyrrole-2-carbonyl}-amino)-ethyl]-carbamic acid tert-butyl ester；tert-butyl N-[2-[[1-methyl-4-[(1-methyl-4-nitropyrrole-2-carbonyl)amino]pyrrole-2-carbonyl]amino]ethyl]carbamate
• CAS: 197705-42-3
• 化学式: C₁₉H₂₆N₆O₆
• 分子量: 434.452
• InChiKey: XHZQRQGYFAMGBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-{[(1-methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-1H-pyrrol-2-yl)carbonyl]amino}ethylcarbamate 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成
  参考文献：
  名称：

  Design, synthesis and antibacterial activity of minor groove binders: The role of non-cationic tail groups

  摘要：

  The design and synthesis of a new class of minor groove binder (MGBs) in which, the cationic tail group has been replaced by a neutral, polar variant including cyanoguanidine, nitroalkene, and trifluoroacetamide groups. Antibacterial activity (against Gram positive bacteria) was found for both the nitroalkene and trifluoroacetamide groups. For the case of the nitroalkene tail group, strong binding of a minor groove binder containing this tail group was demonstrated by both DNA footprinting and melting temperature measurements, showing a correlation between DNA binding and antibacterial activity. The compounds have also been evaluated for binding to the hERG ion channel to determine whether non-cationic but polar substituents might have an advantage compared with conventional cationic tail groups in avoiding hERG binding. In this series of compounds, it was found that whilst non-cationic compounds generally had lower affinity to the hERG ion channel, all of the compounds studied bound weakly to the hERG ion channel, probably associated with the hydrophobic head groups. (c) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.013
• 作为产物：
  描述：

  1-甲基-4-硝基吡咯-2-羧酸 在 吡啶 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 3.67h， 生成 tert-butyl 2-{[(1-methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-1H-pyrrol-2-yl)carbonyl]amino}ethylcarbamate
  参考文献：
  名称：

  Structure-activity relationship of a series of C-terminus modified aminoalkyl, diaminoalkyl- and anilino-containing analogues of the benzoic acid mustard distamycin derivative tallimustine: Synthesis, DNA binding and cytotoxicity studies

  摘要：

  As part of our investigations into the design of more cytotoxic analogues of the experimental anticancer drug tallimustine, 1, C-terminus modified aminoalkyl-, 2a-c, diaminoalkyl-, 3, and anilino-containing, 4, derivatives have been synthesized. Compounds 2a-c differ by 2, 3, or 4 methylene units in the C-terminus, respectively. Results from an ethidium displacement study on poly(dA-dT), poly(dG-dC), calf thymus DNA and T4 coliphage DNA showed that compounds 2-4 interact in the minor groove of the polynucleotides with a preference for poly(dA-dT) over poly(dG-dC). Compound 4 bound more weakly to the DNAs than 2a-c and 3. Using a CD dilution assay compounds 2a-c and 3 were demonstrated to bind irreversibly to calf thymus DNA. The sequence selectivity by which compounds 2-4 alkylate DNA was demonstrated using a Tag polymerase stop assay. All the compounds alkylated preferentially at the 3'-purine residue in a 5'-TTTTGPu-3' sequence (Pu = A or G). This observed sequence specificity is similar to that of tallimustine and a related compound 5. At an equimolar concentration the aminoalkyl compounds 2a-c (2b > 2a > 2c), and diaminoalkyl compound 3 were more efficient at alkylating these sequences than the anilino compound 4. Following a one hour exposure of human chronic myeloid leukemia K562 cells, compounds 2b and 3 have lower IC50 values (1.64 mu M and 3.03 mu M, respectively) than tallimustine (5 mu M) and similar Values to a related compound 5 (2.2 mu M). The order of cytotoxicity for all the compounds is 2b > 5 > 3 > 2a > 1 > 2c = 4. These results indicate that the cytotoxicities of these compounds are related to their relative ability to alkylate the consensus DNA binding sequence. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00096-5

文献信息

• [EN] SEQUENCE SELECTIVE PYRROLE AND IMIDAZOLE POLYAMIDE METALLOCOMPLEXES<br/>[FR] MÉTALLOCOMPLEXES POLYAMIDES DE PYRROLE ET IMIDAZOLE SELECTIFS VIS-A-VIS DE SEQUENCES
  申请人：UNIV WESTERN SYDNEY

  公开号：WO2005033077A1

  公开（公告）日：2005-04-14

  The present invention relates to sequence selective compounds for targeting therapeutic or diagnostic groups to polynucleotides. More particularly, the present invention relates to sequence selective targeting of metallocomplexes, such as metallodrugs and metallodiagnostics, to polynucleotides.

  本发明涉及用于将治疗或诊断组靶向到多核苷酸的序列选择性化合物。更具体地说，本发明涉及将金属配合物（如金属药物和金属诊断试剂）的序列选择性靶向到多核苷酸。
• Cytotoxic α-Halogenoacrylic Derivatives of Distamycin A and Congeners
  作者：Italo Beria、Pier Giovanni Baraldi、Paolo Cozzi、Marina Caldarelli、Cristina Geroni、Sergio Marchini、Nicola Mongelli、Romeo Romagnoli

  DOI：10.1021/jm031051k

  日期：2004.5.1

  action of many antitumor agents involves DNA damage, either by direct binding of the drug to DNA or to DNA-binding proteins. However, most of the DNA-interacting agents have only a limited degree of sequence specificity, which implies that they may hit all the cellular genes. DNA minor groove binders, among which the derivatives of distamycin A play an important role, could provide significant improvement

  许多抗肿瘤药的作用机制都涉及DNA损伤，这可能是由于药物与DNA或与DNA结合蛋白的直接结合而引起的。但是，大多数DNA相互作用剂仅具有有限程度的序列特异性，这意味着它们可能击中所有细胞基因。DNA小沟结合剂（其中双霉素A的衍生物起着重要作用）由于与富含胸腺嘧啶-腺嘌呤（TA）的序列具有很高的选择性，可以显着改善癌症的治疗，增加基因特异性。我们现在报告和讨论合成的，体外和体内活性以及二霉素A的α-卤代丙烯酰胺基衍生物的一些机理特征。这项工作的最终结果是选择brosTAllicin 17（PNU-166196）。BrosTAllicin，目前处于II期临床试验中，与广谱霉素衍生物塔木斯汀相比，它具有广谱的抗肿瘤活性和更高的凋亡作用。与临床测试的DNA小沟结合剂相比，brosTAllicin的重要体外毒理学特征是对人类造血祖细胞的骨髓毒性与对肿瘤细胞的细胞毒性之间的比率非常高。brosTAll
• Sequence Selective Pyrrole and Imidazole Polyamide Metallocomplexes
  申请人：Jaramillo David

  公开号：US20070265240A1

  公开（公告）日：2007-11-15

  The present invention relates to sequence selective compounds for targeting therapeutic or diagnostic groups to polynucleotides. More particularly, the present invention relates to sequence selective targeting of metallocomplexes, such as metallodrugs and metallodiagnostics, to polynucleotides.

  本发明涉及用于将治疗或诊断药物组选择性地定向到多核苷酸的序列选择性化合物。更具体地，本发明涉及将金属配合物（如金属药物和金属诊断剂）的序列选择性定向到多核苷酸。
• SEQUENCE SELECTIVE PYRROLE AND IMIDAZOLE POLYAMIDE METALLOCOMPLEXES
  申请人：University of Western Sydney

  公开号：EP1678133A1

  公开（公告）日：2006-07-12
• EP1678133A4
  申请人：——

  公开号：EP1678133A4

  公开（公告）日：2008-06-18