门冬氨酸鸟氨酸相关杂质异构体3 | 63277-12-3

• 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
• 中文名称: 门冬氨酸鸟氨酸相关杂质异构体3
• 英文名称: H-L-Arg-L-Arg-NH2
• 英文别名: N~5~-(Diaminomethylidene)-L-ornithyl-N~5~-(diaminomethylidene)-L-ornithinamide；(2S)-2-amino-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-5-(diaminomethylideneamino)pentanamide
• CAS: 63277-12-3
• 化学式: C₁₂H₂₇N₉O₂
• 分子量: 329.405
• InChiKey: KQFIWXHYCHBRJW-YUMQZZPRSA-N

物化性质

• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  227
• 氢给体数：
  7
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  sofalcone 、 门冬氨酸鸟氨酸相关杂质异构体3 在 F₆P^(1-)*C₁₅H₂₀N₅O⁽¹⁺⁾ 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以94%的产率得到(S)-N-((S)-1-amino-5-guanidino-1-oxopentan-2-yl)-5-guanidino-2-(2-(5-((3-methylbut-2-en-1-yl)oxy)-2-((E)-3-(4-((3-methylbut-2-en-1-yl)oxy)phenyl)acryloyl)phenoxy)acetamido)pentanamide
  参考文献：
  名称：

  设计，合成和评估作为有效的革兰氏阳性抗菌剂的两亲sofalcone衍生物。

  摘要：

  迫切需要新的抗菌剂来克服耐药细菌感染。在这里，我们描述了作为抗菌肽模拟物的一类新的两亲soficone化合物的设计，合成和评估。具有两个精氨酸残基的最有前途的化合物14表现出较差的溶血活性，低细胞毒性和对革兰氏阳性细菌（包括MRSA）的优异抗菌活性。化合物14在各种盐条件下均具有良好的稳定性，可通过直接破坏细菌细胞膜迅速杀死细菌，并且对细菌的耐药性发展较慢。另外，化合物14在由以下原因引起的细菌性角膜炎的鼠模型中显示出有效的体内功效。金黄色葡萄球菌ATCC29213。我们的研究表明，化合物14具有潜在的潜力，可以用作对抗耐药革兰氏阳性细菌的新型抗菌剂。

  DOI：

  10.1016/j.ejmech.2020.112596

文献信息

• Synthesis and biological evaluation of indole-based peptidomimetics as antibacterial agents against Gram-positive bacteria
  作者：Yongzhi Chen、Hongxia Li、Jiayong Liu、Rongcui Zhong、Haizhou Li、Shanfang Fang、Shouping Liu、Shuimu Lin

  DOI：10.1016/j.ejmech.2021.113813

  日期：2021.12

  multidrug resistance and the lack of new antimicrobial agents urgently demand the discovery and development of novel antibacterials that avoid bacterial resistance. Antimicrobial peptidomimetics represent a promising approach for overcoming antibiotic resistance. Herein we report the synthesis and evaluation of indole-based amphiphilic antimicrobial peptidomimetics, bearing hydrophobic side chains and hydrophilic

  细菌多药耐药性的出现和新型抗菌药物的缺乏迫切需要发现和开发能够避免细菌耐药性的新型抗菌药物。抗菌肽模拟物代表了一种有前景的克服抗生素耐药性的方法。在此，我们报告了基于吲哚的两亲抗菌肽模拟物的合成和评估，该肽模拟物具有疏水侧链和亲水阳离子部分。在这些衍生物中，化合物28表现出对革兰氏阳性菌的有效抗菌活性、对哺乳动物细胞的低溶血活性和低毒性，以及在盐条件下的良好稳定性。此外，化合物28显示通过膜靶向作用快速杀死细菌而不会产生细菌耐药性。更重要的是，化合物28在细菌性角膜炎小鼠模型中显示出对革兰氏阳性细菌的高抗菌效力，并且被发现比万古霉素更有效。因此，化合物28作为治疗革兰氏阳性细菌感染的有前途的先导化合物具有巨大的潜力。
• Vancomycin–Arginine Conjugate Inhibits Growth of Carbapenem-Resistant <i>E. coli</i> and Targets Cell-Wall Synthesis
  作者：Alexandra Antonoplis、Xiaoyu Zang、Tristan Wegner、Paul A. Wender、Lynette Cegelski

  DOI：10.1021/acschembio.9b00565

  日期：2019.9.20

  The emergence of multi-drug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae, is a major health problem that necessitates the development of new antibiotics. Vancomycin inhibits cell-wall synthesis in Gram-positive bacteria but is generally ineffective against Gram-negative bacteria and is unable to penetrate the outer membrane barrier. In an effort to determine whether vancomycin and other antibiotics effective against Gram-positive bacteria could, through modification, be rendered effective against Gram-negative bacteria, we discovered that the covalent attachment of a single arginine to vancomycin yielded conjugates with order-of-magnitude improvements in activity against Gram-negative bacteria, including pathogenic E. coli. The vancomycin-arginine conjugate (V-R) exhibited efficacy against actively growing bacteria, induced the loss of rod cellular morphology, and resulted in the intracellular accumulation of peptidoglycan precursors, all consistent with cell-wall synthesis disruption as its mechanism of action. Membrane permeabilization studies demonstrated an enhanced outer membrane permeability of V-R as compared with vancomycin. The conjugate exhibited no mammalian cell toxicity or hemolytic activity in MTT and hemolysis assays. Our study introduces a new vancomycin derivative effective against Gram-negative bacteria and underscores the broader potential of generating new antibiotics through combined mode-of-action and synthesis-informed design studies.
• THIOCYCLOHEPTYNE DERIVATIVES AND THEIR USE
  申请人：Cristal Delivery B.V.

  公开号：US20210395216A1

  公开（公告）日：2021-12-23

  The present invention pertains to novel thiocycloheptyne derivatives of general formula (I): and in particular to thiacycloalkynesulfoimine derivatives and their synthesis. The invention also relates to the use of the novel thiocycloheptyne derivatives in coupling reactions with linkers and drugs. The invention further relates to the use of the novel thiocycloheptynes in bioorthogonal (copper-free) click reactions. The invention further pertains to the use of the novel thiocycloheptyne derivatives in the generation of advanced multifunctional drug delivery systems (drug-loaded) nanoparticles.
• Design, synthesis, and evaluation of amphiphilic sofalcone derivatives as potent Gram-positive antibacterial agents
  作者：Shuimu Lin、Yongzhi Chen、Hongxia Li、Jiayong Liu、Shouping Liu

  DOI：10.1016/j.ejmech.2020.112596

  日期：2020.9

  New antimicrobial agents are urgently needed to overcome drug-resistant bacterial infections. Here we describe the design, synthesis and evaluation of a new class of amphiphilic sofalcone compounds as antimicrobial peptidomimetics. The most promising compound 14, bearing two arginine residues, showed poor hemolytic activity, low cytotoxicity, and excellent antimicrobial activity against Gram-positive

  迫切需要新的抗菌剂来克服耐药细菌感染。在这里，我们描述了作为抗菌肽模拟物的一类新的两亲soficone化合物的设计，合成和评估。具有两个精氨酸残基的最有前途的化合物14表现出较差的溶血活性，低细胞毒性和对革兰氏阳性细菌（包括MRSA）的优异抗菌活性。化合物14在各种盐条件下均具有良好的稳定性，可通过直接破坏细菌细胞膜迅速杀死细菌，并且对细菌的耐药性发展较慢。另外，化合物14在由以下原因引起的细菌性角膜炎的鼠模型中显示出有效的体内功效。金黄色葡萄球菌ATCC29213。我们的研究表明，化合物14具有潜在的潜力，可以用作对抗耐药革兰氏阳性细菌的新型抗菌剂。