(3-nitro)-L-phenylalanine methyl ester hydrochloride | 20299-36-9

• 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: (3-nitro)-L-phenylalanine methyl ester hydrochloride
• 英文别名: methyl (S)-2-amino-3-(3-nitrophenyl)propanoate hydrochloride；H-Phe(3-NO₂)-OMe*HCl；3-Nitro-L-phenylalanine methyl ester HCl；methyl (2S)-2-amino-3-(3-nitrophenyl)propanoate;hydrochloride
• CAS: 20299-36-9
• 化学式: C₁₀H₁₂N₂O₄*ClH
• 分子量: 260.677
• InChiKey: HQZBPSISFPOYIS-FVGYRXGTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.06
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  98.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-nitro)-L-phenylalanine methyl ester hydrochloride 在 溶剂黄146 、 sodium hydroxide 、 锌 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.34h， 生成
  参考文献：
  名称：

  Development of New Cyclic Plasmin Inhibitors with Excellent Potency and Selectivity

  摘要：

  The trypsin-like serine protease plasmin is a target for the development of antifibrinolytic drugs for use in cardiac surgery with cardiopulmonary bypass or organ transplantations to reduce excessive blood loss. The optimization of our recently described substrate-analogue plasmin inhibitors, which were cyclized between their P3 and P2 side chains, provided a new series with improved efficacy and excellent selectivity. The most potent inhibitor 8 binds to plasmin with an inhibition constant of 0.2 nM, whereas K-i values >1 mu M were determined for nearly all other tested trypsin-like serine proteases, with the exception of trypsin, which is also inhibited in the nanomolar range. Docking studies revealed a potential binding mode in the widely open active site of plasmin that explains the strong potency and selectivity profile of these inhibitors. The dialkylated piperazine-linker segment contributes to an excellent solubility of all analogues. Based on their overall profile the presented inhibitors are well suited for further development as injectable antifibrinolytic drugs.

  DOI：

  10.1021/jm3012917
• 作为产物：
  描述：

  甲醇 、 3-硝基-L-苯丙氨酸 在 氯化亚砜 作用下， 反应 4.0h， 以100%的产率得到(3-nitro)-L-phenylalanine methyl ester hydrochloride
  参考文献：
  名称：

  苯丙氨酸和苯甘氨酸类似物作为登革热蛋白酶抑制剂中的精氨酸模拟物

  摘要：

  登革热病毒是一种日益全球性的病原体。针对登革热和相关黄病毒（例如西尼罗河病毒）的抗病毒药物发现的有希望的目标之一是病毒丝氨酸蛋白酶NS2B-NS3。我们在这里报告了登革热病毒蛋白酶的强肽抑制剂的合成和体外表征，该抑制剂结合了苯丙氨酸和苯甘氨酸衍生物作为具有调节碱性的精氨酸模拟基团。最有前途的化合物是（4-脒基） -升-含苯丙氨酸的抑制剂，对登革热病毒蛋白酶达到纳摩尔亲和力。苯基甘氨酸和苯丙氨酸侧链上的取代基的类型和位置对针对登革热病毒蛋白酶的抑制活性和对其他蛋白酶的选择性具有显着影响。另外，本文所述的非天然碱性氨基酸可能与其他肽类和拟肽类药物的开发有关，例如凝血级联的抑制剂。

  DOI：

  10.1021/acs.jmedchem.5b00612

文献信息

• Peptide–Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology
  作者：Christoph Nitsche、Linlin Zhang、Lena F. Weigel、Jonas Schilz、Dominik Graf、Ralf Bartenschlager、Rolf Hilgenfeld、Christian D. Klein

  DOI：10.1021/acs.jmedchem.6b01021

  日期：2017.1.12

  A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Structure–activity relationships and a high resolution X-ray cocrystal structure with West Nile virus protease

  通过将C末端硼酸部分引入Zika，West Nile和登革热病毒蛋白酶的二肽抑制剂中，可以实现千倍的亲和力提高。所得化合物的K i值在两位数纳摩尔范围内，无细胞毒性，并抑制病毒复制。与西尼罗河病毒蛋白酶的结构活性关系和高分辨率X射线共晶体结构为针对新兴黄病毒病原体的优化共价可逆抑制剂的设计提供了基础。
• [EN] PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉASE
  申请人：[en]PROTINHI B.V.

  公开号：WO2023052636A1

  公开（公告）日：2023-04-06

  The present invention relates to a new class of compounds based on alkylated oligopeptides featuring distinct head and tail modifications at their termini. The compounds are useful as inhibitors of viral proteases, particularly of flaviviral proteases, and can therefore be used for treatment of viral infections.