N-(5-{[(3-amino-3-iminopropyl)amino]-carbonyl}-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide | 23999-80-6

• 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: N-(5-{[(3-amino-3-iminopropyl)amino]-carbonyl}-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide
• 英文别名: 3-<1-Methyl-4-(1-methyl-4-nitro-pyrrol-(2)-carboxamido)-2-pyrrolcarboxamido>-propionamidin；N-(3-amino-3-iminopropyl)-1-methyl-4-[(1-methyl-4-nitropyrrole-2-carbonyl)amino]pyrrole-2-carboxamide
• CAS: 23999-80-6
• 化学式: C₁₅H₁₉N₇O₄
• 分子量: 361.36
• InChiKey: GPMPQMAABOKVML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  164
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(5-{[(3-amino-3-iminopropyl)amino]-carbonyl}-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide 在 palladium on activated charcoal 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 13.5h， 生成 3-(1-methyl-4-<1-methyl-4<4-(2-<7,10,12-trimethyl-6H-<1,3>oxazolo<5,4-c>pyrido<3,4-g>-carbazole>)butylcarboxamido>pyrrole-2-carboxamido>pyrrole-2-carboxamido)propionamidine bis-(acetate)
  参考文献：
  名称：

  Synthesis, DNA binding and biological activity of oxazolopyridocarbazole-netropsin hybrid molecules

  摘要：

  A series of bifunctional molecules have been synthesized which result from the combination of a DNA sequence-specific ligand (netropsin) coupled to an intercalator moiety (OPC). The binding constants to double-stranded polynucleotides as well as the cytostatic activity against both murine and human tumor cell lines and the in vitro activity against a range of DNA and RNA viruses (including human immunodeficiency virus) have been determined for these novel molecules. All of them retain the DNA binding affinity of netropsin but with a notable decrease of A-T sequence selectivity. They did not show in vitro antiviral activity. On the other hand, these compounds demonstrated enhanced cytostatic activity against both human and murine tumor cell lines.

  DOI：

  10.1016/0223-5234(91)90143-b

文献信息

• Antimicrobial Lexitropsins Containing Amide, Amidine, and Alkene Linking Groups
  作者：Nahoum G. Anthony、David Breen、Joanna Clarke、Gavin Donoghue、Allan J. Drummond、Elizabeth M. Ellis、Curtis G. Gemmell、Jean-Jacques Helesbeux、Iain S. Hunter、Abedawn I. Khalaf、Simon P. Mackay、John A. Parkinson、Colin J. Suckling、Roger D. Waigh

  DOI：10.1021/jm070831g

  日期：2007.11.1

  -resistant strains, in the range of 0.1-5 microg mL-1, which is comparable to many established antibacterial agents. Antifungal activity was also found in the range of 20-50 microg mL-1 MIC against Aspergillus niger and Candida albicans, again comparable with established antifungal drugs. A quinoline derivative was found to protect mice against S. aureus infection for a period of up to six days after a single

  描述了80种与二霉素和噻唑类相关的短小沟结合剂的合成和性能。化合物的设计主要基于小沟结合剂和DNA之间的疏水相互作用而增加的亲和力。疏水性芳族头基（包括喹啉基和苯甲酰基衍生物）的引入以及烯烃作为连接剂的引入，导致几种具有MIC的金黄色葡萄球菌的强活性抗菌化合物（对甲氧西林敏感和耐药的菌株）范围为0.1-5 microg mL -1，与许多已建立的抗菌剂相当。还发现针对黑曲霉和白色念珠菌的抗真菌活性为20-50微克mL-1 MIC，再次与已确立的抗真菌药物相当。
• Novel Minor Groove Binders Cure Animal African Trypanosomiasis in an in Vivo Mouse Model
  作者：Federica Giordani、Abedawn I. Khalaf、Kirsten Gillingwater、Jane C. Munday、Harry P. de Koning、Colin J. Suckling、Michael P. Barrett、Fraser J. Scott

  DOI：10.1021/acs.jmedchem.8b01847

  日期：2019.3.28

  Animal African trypanosomiasis (AAT) is a significant socioeconomic burden for sub-Saharan Africa because of its huge impact on livestock health. Existing therapies including those based on minor groove binders (MGBs), such as the diamidines, which have been used for decades, have now lost efficacy in some places because of the emergence of resistant parasites. Consequently, the need for new chemotherapies

  动物非洲锥虫病 (AAT) 是撒哈拉以南非洲的重大社会经济负担，因为它对牲畜健康产生巨大影响。现有疗法，包括基于小沟结合剂 (MGB) 的疗法，例如已经使用了数十年的二脒，现在由于耐药寄生虫的出现而在某些地方失去了疗效。因此，迫切需要新的化学疗法。在这里，我们描述了结构不同的一类 MGB，Strathclyde MGB (S-MGB)，它们对 AAT 的主要致病生物表现出出色的体外活性：刚果锥虫和间日锥虫。我们还展示了许多这些化合物对 T. congolense 感染小鼠的治疗。特别是，我们通过两次腹腔注射 50 mg/kg 将 S-MGB-234（化合物 7）鉴定为治疗剂。至关重要的是，我们证明 S-MGB 不显示与当前二脒药物的交叉耐药性，并且不会通过二脒使用的转运蛋白内化。这项研究表明，S-MGBs 作为 AAT 的新型治疗剂具有巨大的潜力。
• Synthesis, DNA binding and biological activity of oxazolopyridocarbazole-netropsin hybrid molecules
  作者：D Mrani、G Gosselin、C Auclair、J Balzarini、E De Clercq、C Paoletti、JL Imbach

  DOI：10.1016/0223-5234(91)90143-b

  日期：1991.7

  A series of bifunctional molecules have been synthesized which result from the combination of a DNA sequence-specific ligand (netropsin) coupled to an intercalator moiety (OPC). The binding constants to double-stranded polynucleotides as well as the cytostatic activity against both murine and human tumor cell lines and the in vitro activity against a range of DNA and RNA viruses (including human immunodeficiency virus) have been determined for these novel molecules. All of them retain the DNA binding affinity of netropsin but with a notable decrease of A-T sequence selectivity. They did not show in vitro antiviral activity. On the other hand, these compounds demonstrated enhanced cytostatic activity against both human and murine tumor cell lines.