β-Nitrovaline | 170454-20-3

• 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: β-Nitrovaline
• 英文别名: (+/-)-nitrovaline；2-amino-3-methyl-3-nitrobutanoic acid；(D,L)-3-nitrovaline；3-Nitro-valine
• CAS: 170454-20-3
• 化学式: C₅H₁₀N₂O₄
• 分子量: 162.145
• InChiKey: SVQLBNMIYIBLOU-UHFFFAOYSA-N

物化性质

• 沸点：
  299.5±35.0 °C(Predicted)
• 密度：
  1.322±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  β-Nitrovaline 在 氯化亚砜 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 锌 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 216.67h， 生成
  参考文献：
  名称：

  Design, Synthesis, and Properties of a Potent Inhibitor of Pseudomonas aeruginosa Deacetylase LpxC

  摘要：

  Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.

  DOI：

  10.1021/acs.jmedchem.7b00377
• 作为产物：
  描述：

  (+/-)-3-nitrovaline hydrochloride 在 苯胺 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以46%的产率得到β-Nitrovaline
  参考文献：
  名称：

  Synthesis of side-chain functionalized amino acid derivatives through reaction of alkyl nitronates with α-bromoglycine derivatives

  摘要：

  Reactions of alkyl nitronates with alpha-bromoglycine derivatives provide access to a variety of halo-, beta-nitro- and alpha,beta-dehydro-alpha-amino acid derivatives, including beta-functionalized alpha,beta-dehydroamino acid derivatives. The hydrochloride salts of free beta-nitro-alpha-amino acids can also be prepared using this approach.

  DOI：

  10.1016/0040-4020(95)00398-r

文献信息

• [EN] ORGANIC COMPOUNDS FOR APPLICATIONS IN BACTERIAL INFECTIONS TREATMENT<br/>[FR] COMPOSÉS ORGANIQUES DESTINÉS À ÊTRE APPLIQUÉS DANS LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：NOVARTIS AG

  公开号：WO2010031750A1

  公开（公告）日：2010-03-25

  The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of human diseases.

  本申请描述了对治疗、预防及/or改善人类疾病的有机化合物。
• [EN] UREA DERIVATIVES AS ANTIBACTERIAL AGENTS<br/>[FR] DÉRIVÉS D'URÉE EN TANT QU'AGENTS ANTIBACTÉRIENS
  申请人：SCHERING CORP

  公开号：WO2010017060A1

  公开（公告）日：2010-02-11

  This invention relates to compounds of the Formula (I):or a pharmaceutically acceptable salt, solvate, ester or isomer thereof, which is useful for the treatment of diseases or conditions mediated by LpxC.

  这项发明涉及以下化合物的结构（I）：或其药用盐、溶剂合物、酯或异构体，用于治疗由LpxC介导的疾病或症状。
• A one-pot three-component synthesis of β-nitro-α-amino acids and their N-alkyl derivatives
  作者：Phillip A. Coghlan、Christopher J. Easton

  DOI：10.1039/a906223h

  日期：——

  A water-based condensation of glyoxylic acid, nitroalkanes and amines is described, offering a straightforward synthesis of β-nitro-α-amino acids and their N-alkyl derivatives.

  介绍了一种乙醛酸、硝基烷烃和胺的水基缩合物，可直接合成 δ-硝基-δ-氨基酸及其 N-烷基衍生物。
• ANTIBACTERIAL AGENTS
  申请人：Moser Heinz E.

  公开号：US20100190766A1

  公开（公告）日：2010-07-29

  Antibacterial compounds of formula (I) are provided: as well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.

  提供化学式(I)的抗菌化合物：以及其立体异构体，药学上可接受的盐，酯和前药；包含这些化合物的制药组合物；通过给予这些化合物的途径治疗细菌感染的方法；以及制备这些化合物的过程。
• The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition
  作者：Timm O. Koller、Ullrich Scheid、Teresa Kösel、Jennifer Herrmann、Daniel Krug、Helena I. M. Boshoff、Bertrand Beckert、Joanna C. Evans、Jan Schlemmer、Becky Sloan、Danielle M. Weiner、Laura E. Via、Atica Moosa、Thomas R. Ioerger、Michael Graf、Boris Zinshteyn、Maha Abdelshahid、Fabian Nguyen、Stefan Arenz、Franziska Gille、Maik Siebke、Tim Seedorf、Oliver Plettenburg、Rachel Green、Anna-Luisa Warnke、Joachim Ullrich、Ralf Warrass、Clifton E. Barry、Digby F. Warner、Valerie Mizrahi、Andreas Kirschning、Daniel N. Wilson、Rolf Müller

  DOI：10.1021/jacs.2c08816

  日期：2023.1.18

  bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against Mycobacterium tuberculosis. To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production

  细菌病原体对抗生素的耐药性被世界卫生组织宣布为全球主要健康威胁。由于迫切需要新型抗菌剂，我们重新评估了广谱粘细菌抗生素 myxovalargin，发现它对结核分枝杆菌非常有效. 为了确保进一步开发的化合物供应，我们详细研究了 myxovalargin 生物合成，从而能够通过本地生产者的发酵进行生产。喂养实验和功能基因组学分析提出了结构修正，最终通过简明全合成的发展得到证实。基于抗性突变测序，核糖体被确定为分子靶标，冷冻电镜结构显示 myxovalargin 在出口隧道内结合并完全封闭出口隧道，这与在翻译起始后期阻止翻译的作用模式一致。这些研究为基于结构的支架改进开发抗菌剂开辟了道路。