肼羧酸,2-(3-甲基丁基)-,1,1-二甲基乙基酯(9CI) | 180462-81-1

• 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: 肼羧酸,2-(3-甲基丁基)-,1,1-二甲基乙基酯(9CI)
• 中文别名: 2-甲基-2-丙基2-(3-甲基丁基)肼羧酸酯
• 英文名称: N'-(3-methylbutyl)hydrazinecarboxylic acid tert-butyl ester
• 英文别名: tert-Butyl 2-isopentylhydrazinecarboxylate；tert-butyl N-(3-methylbutylamino)carbamate
• CAS: 180462-81-1
• 化学式: C₁₀H₂₂N₂O₂
• 分子量: 202.297
• InChiKey: MLNIZGCXZSQUCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	tert-butyl 2-isobutylhydrazinecarboxylate	57699-53-3	C9H20N2O2	188.27
  肼基甲酸叔丁酯	t-butoxycarbonylhydrazine	870-46-2	C5H12N2O2	132.162

反应信息

• 作为反应物：
  描述：

  肼羧酸,2-(3-甲基丁基)-,1,1-二甲基乙基酯(9CI) 在 1,4-二氧六环 、 盐酸 作用下， 以 甲醇 为溶剂， 反应 22.0h， 生成 (2S,3S)-3-Amino-1-[N-(3-methyl-butyl)-hydrazino]-4-phenyl-butan-2-ol; hydrochloride
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p
• 作为产物：
  描述：

  N'-(3-methylbutylidene)hydrazinecarboxylic acid tert-butyl ester 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 以52%的产率得到肼羧酸,2-(3-甲基丁基)-,1,1-二甲基乙基酯(9CI)
  参考文献：
  名称：

  丙型肝炎病毒丝氨酸蛋白酶的新型氮杂肽抑制剂。

  摘要：

  氮杂肽是几种丝氨酸和半胱氨酸蛋白酶的已知抑制剂。在寻找HCV丝氨酸蛋白酶的不同类别的抑制剂时，研究了一系列新的基于氮杂肽的抑制剂，它们掺入了不可裂解的P1 / P1'氮杂-氨基酰基残基。围绕P1 / P1'氮杂氨基酰基片段的SAR研究广泛，导致了有效抑制剂和选择性抑制剂的鉴定。使用NMR研究，我们显示了这一系列抑制剂以非共价竞争方式与NS3蛋白酶活性位点结合。使用转移NOE技术确定了这些新的基于氮杂肽的抑制剂之一的结合构象。这些新的氮杂-氨基酰基官能团在P1位置的掺入为探查酶S'区的新相互作用提供了一个方便的方法。

  DOI：

  10.1021/jm049864b

文献信息

• Falcipain Inhibitors: Optimization Studies of the 2-Pyrimidinecarbonitrile Lead Series
  作者：Jose M. Coterón、David Catterick、Julia Castro、María J. Chaparro、Beatriz Díaz、Esther Fernández、Santiago Ferrer、Francisco J. Gamo、Mariola Gordo、Jiri Gut、Laura de las Heras、Jennifer Legac、Maria Marco、Juan Miguel、Vicente Muñoz、Esther Porras、Juan C. de la Rosa、Jose R. Ruiz、Elena Sandoval、Pilar Ventosa、Philip J. Rosenthal、Jose M. Fiandor

  DOI：10.1021/jm100556b

  日期：2010.8.26

  were studied as potential falcipain inhibitors and therefore potential antiparasitic lead compounds, with the 5-substituted-2-cyanopyrimidine chemical class emerging as the most potent and promising lead series. Through a sequential lead optimization process considering the different positions present in the initial scaffold, nanomolar and subnanomolar inhibitors at falcipains 2 and 3 were identified

  Falcipain-2和falcipain-3是疟原虫恶性疟原虫的木瓜蛋白酶家族半胱氨酸蛋白酶负责宿主血红蛋白水解以提供用于寄生虫蛋白质合成的氨基酸。研究了不同的杂芳基腈衍生物作为潜在的falcipain抑制剂，因此潜在的抗寄生虫铅化合物，其中5-取代的2-氰基嘧啶化学类别成为最有效和有前途的铅系列。考虑到初始支架中存在的不同位置，通过顺序的前导优化过程，鉴定出了在恶性激素2和3处的纳摩尔和亚纳摩尔抑制剂，并具有在微摩尔范围内对抗培养的寄生虫的活性。在铅分子中引入质子化胺后，对培养的寄生虫的活性显着提高了1000倍，而其他SAR趋势没有明显改变。
• Combinatorial Aid for Underprivileged Scaffolds: Solution and Solid-phase Strategies for a Rapid and Efficient Access To Novel Aza-diketopiperazines (Aza-DKP)
  作者：Dominique Bonnet、Jean-François Margathe、Sally Radford、Elsa Pflimlin、Stéphanie Riché、Pete Doman、Marcel Hibert、A. Ganesan

  DOI：10.1021/co300015k

  日期：2012.5.14

  An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP, triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly-Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4-triazine-3,6-diones has been synthesized starting from Fmoc-L-Pro-OH and various Fmoc-L-amino acids. To extend the practical value of this class of dipeptidomimetics, a general solid-phase synthesis approach amenable to library production was developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the resins in TFA/water mixture at room temperature enabled the rapid and quantitative cyclization/release highly pure triazinediones. The conformational preferences and the spatial organization of the three substituents of a representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by X-ray diffraction and H-1 NMR spectroscopy.
• Petasis boronic acid–Mannich reactions of substituted hydrazines: synthesis of α-hydrazinocarboxylic acids
  作者：David E. Portlock、Dinabandhu Naskar、Laura West、Min Li

  DOI：10.1016/s0040-4039(02)01511-3

  日期：2002.9

  N-1-(Carbamate protected)-N-2-(alkyl or aryl substituted) hydrazines can serve as amine substrates for the Petasis boronic acid-Mannich reaction, providing a practical synthetic route for the preparation of alpha-hydrazinocarboxylic acids. The scope and limitations of this method have been examined. (C) 2002 Published by Elsevier Science Ltd.
• QUINONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
  申请人：Indiana University Research and Technology Corporation

  公开号：EP2203161B1

  公开（公告）日：2018-05-09
• PHOSPHADIAZINE HCV POLYMERASE INHIBITORS III AND VI
  申请人：Dousson Cyril

  公开号：US20090060867A1

  公开（公告）日：2009-03-05

  Provided herein are phosphadiazine polymerase inhibitor, for example, of Formula III, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.