benzyl 2-isobutylhydrazine-1-carboxylate | 135942-00-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl 2-isobutylhydrazine-1-carboxylate
• 英文别名: Hydrazinecarboxylic acid, 2-(2-methylpropyl)-, phenylmethyl ester；benzyl N-(2-methylpropylamino)carbamate
• CAS: 135942-00-6
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: HHGQBJXUUOIDKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl 2-isobutylhydrazine-1-carboxylate 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 22.5h， 生成 benzyl N-[2,2-dimethoxypropylcarbamoyl(2-methylpropyl)amino]carbamate
  参考文献：
  名称：

  Peptidyl and azapeptidyl methylketones as substrate analog inhibitors of papain and cathepsin B

  摘要：

  Peptidyl methylketones containing Phe, Tyr, Tyr(I) Tyr(I-2), Leu and Ile in P-2 were synthesized and tested as substrate analog reversible inhibitors of papain and bovine spleen cathepsin B. The most effective cathepsin B inhibitor contained Tyr(I-2) and displayed an inhibition constant of 4.7 mu M at pH 6.8 and 25 degrees C, while Leu or lie gave practically inert analogs. Replacement of the amino acids in P-2 with the analogous alpha-azaamino acids, as well as the glycine in P-1 with alpha-azaglycine, led to complete loss of inhibiting activity. Introducing alkoxy substituents at the methyl adjacent to the ketone group generally resulted in more effective inhibitors, with inhibition constants in the micromolar range for both papain and cathepsin B.

  DOI：

  10.1016/0223-5234(96)88312-7
• 作为产物：
  描述：

  肼基甲酸苄酯 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 30.0h， 生成 benzyl 2-isobutylhydrazine-1-carboxylate
  参考文献：
  名称：

  E-64C-酰肼：期不可逆的组织蛋白酶C抑制剂的开发引线结构

  摘要：

  组织蛋白酶C是一种具有二肽基氨基肽酶活性的木瓜蛋白酶样半胱氨酸蛋白酶，被认为可以激活各种颗粒相关的丝氨酸蛋白酶。它的肽外切酶活性在结构上由所谓的排斥结构域解释，该结构域阻止S2位点以外的活性位点裂口，并带有Asp 1残基，为肽和蛋白质底物的N端提供锚定点。此处的（2 S，3 S）-反式-环氧琥珀酰-L-亮氨酰胺基-3-甲基丁烷（E-64c）的酰肼（k 2 / K i = 140±5  M -1  s -1）被证明是开发不可逆组织蛋白酶C抑制剂的先导结构。远端氨基的酰肼部分的地址在S2口袋的通过氢键入口处的酸性天冬氨酸1个残基，同时还占据平面疏水S1'-S2'与它的亮氨酸isoamylamide部分区域。此外，结构与活性之间的关系研究表明，带有烷基残基的远端氨基官能团可用于占据保守的疏水S2口袋。特别地，Ñ丁基衍生物被确定为系列中最有效的抑制剂（ķ 2 / ķ我= 56 000±1700 中号-1 小号-1）。

  DOI：

  10.1002/cmdc.201300093

文献信息

• [EN] INHIBITORS OF NOROVIRUS AND CORONAVIRUS REPLICATION<br/>[FR] INHIBITEURS DE LA RÉPLICATION DE NOROVIRUS ET DE CORONAVIRUS
  申请人：COCRYSTAL PHARMA INC

  公开号：WO2021206876A1

  公开（公告）日：2021-10-14

  Compounds of Formula (I) and methods of inhibiting the replication of viruses in a biological sample or patient, of reducing the amount of viruses in a biological sample or patient, and of treating a virus infection in a patient, comprising administering to said biological sample or patient an effective amount of a compound represented by Formula (I), a compound of Table A or B or a pharmaceutically acceptable salt thereof.

  公式（I）化合物及抑制生物样本或患者中病毒复制、减少生物样本或患者中病毒数量、以及治疗患者病毒感染的方法，包括向所述生物样本或患者投与由公式（I）表示的化合物、表A或B中的化合物或其药用可接受盐的有效量。
• Photocatalytic C–O Bond Cleavage of Alcohols Using Xanthate Salts
  作者：Takeshi Nanjo、Tatsuki Matsugasako、Yuri Maruo、Yoshiji Takemoto

  DOI：10.1021/acs.orglett.1c04029

  日期：2022.1.14

  alkyl radicals is an attractive yet challenging transformation in organic synthesis. Herein we describe a photocatalyzed deoxygenative C–C coupling reaction of xanthate salts, which can be easily prepared from the corresponding alcohols. The key to the success of this strategy is the low oxidation potential of the xanthate salt and the use of an appropriate phosphine to accelerate the desulfurative release

  C-O 键的均裂裂解以提供烷基自由基是有机合成中有吸引力但具有挑战性的转变。在这里，我们描述了黄原酸盐的光催化脱氧 C-C 偶联反应，该反应可以很容易地从相应的醇中制备。该策略成功的关键是黄原酸盐的低氧化电位和使用合适的磷化氢来加速羰基硫的脱硫释放。
• Proteolytically Stable Diaza-Peptide Foldamers Mimic Helical Hot Spots of Protein–Protein Interactions and Act as Natural Chaperones
  作者：Chenghui Shi、Julia Kaffy、Tâp Ha-Duong、Jean-François Gallard、Alain Pruvost、Aloise Mabondzo、Lidia Ciccone、Sandrine Ongeri、Nicolo Tonali

  DOI：10.1021/acs.jmedchem.3c00611

  日期：2023.9.14

  these foldamers to resist proteolysis, to mimic the small helical hot spot of transthyretin-amyloid β (Aβ) cross-interaction, and to decrease pathological Aβ aggregation demonstrates that the introduction of diaza-peptide units is a valid approach for designing mimics or inhibitors of protein–protein interaction and other therapeutic peptidomimetics. This study also reveals that small peptide foldamers

  报道了一类基于二氮杂肽单元的新型肽模拟折叠体。圆二色性、衰减全反射 - 傅里叶变换红外、核磁共振和分子动力学研究表明，与天然母体九肽不同，在 N 末端特异性掺入一个二氮杂肽单元可以在水中进行螺旋折叠，这进一步得到了增强在C端引入第二个单元。这些折叠体能够抵抗蛋白水解、模拟运甲状腺素蛋白-淀粉样蛋白 β (Aβ) 交叉相互作用的小螺旋热点以及减少病理性 Aβ 聚集，这表明引入二氮杂肽单元是设计模拟物的有效方法或蛋白质-蛋白质相互作用抑制剂和其他治疗性肽模拟物。这项研究还揭示了小肽折叠体可以起到与生理伴侣蛋白相同的作用，并开辟了设计淀粉样蛋白聚集抑制剂的新方法，淀粉样蛋白聚集是阿尔茨海默氏病等 20 多种严重人类疾病的标志。
• Retro Hydrazino-azapeptoids as Peptidomimetics of Proteasome Inhibitors
  作者：Sandrine Aubin、Bénédicte Martin、Jean-Guy Delcros、Yannick Arlot-Bonnemains、Michèle Baudy-Floc'h

  DOI：10.1021/jm049455f

  日期：2005.1.1

  Several groups of proteasome inhibitors are widely used to study the role of the ubiquin proteasome pathway in various cellular processes or as anticancer drugs. Peptidomimetics have been developed to circumvent problems inherent in peptides such as poor bioavailability and protease-mediated degradation, while retaining biological activity. In this study, we introduce new pseudopeptides, the retro hydrazino-azapeptoids, designed as proteasome inhibitor peptidomimetics. Their proteasome inhibitory activity and antiproliferative properties are reported here.
• Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2‘ Ligands in Pseudosymmetric Dipeptide Isosteres
  作者：G. S. Kiran Kumar Reddy、Akbar Ali、Madhavi N. L. Nalam、Saima Ghafoor Anjum、Hong Cao、Robin S. Nathans、Celia A. Schiffer、Tariq M. Rana

  DOI：10.1021/jm070284z

  日期：2007.9.1

  A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure -activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.