{(1S)-1-[N'-(4-bromobenzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}carbamic acid methyl ester | 872703-59-8

• 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: {(1S)-1-[N'-(4-bromobenzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}carbamic acid methyl ester
• 英文别名: {(S)-1-[N'-(4-bromobenzyl)hydrazinocarbonyl]-2,2-dimethylpropyl}carbamic acid methyl ester；{(1S)-1-[N'-(4-Bromo-benzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}-carbamic acid methyl ester；methyl N-[(2S)-1-[2-[(4-bromophenyl)methyl]hydrazinyl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
• CAS: 872703-59-8
• 化学式: C₁₅H₂₂BrN₃O₃
• 分子量: 372.262
• InChiKey: TVCUUTJYZFEWEU-GFCCVEGCSA-N

物化性质

• 沸点：
  467.1±45.0 °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：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {(1S)-1-[N'-(4-bromobenzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}carbamic acid methyl ester 在 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 3.25h， 以45%的产率得到[(S)-1-(N'-(4-bromobenzyl)-N'-{(R)-4-(tert-butyldimethylsilanyloxy)-4-[(1S,2R)-2-(tert-butyldimethylsilanyloxy)indan-1-ylcarbamoyl]-5-phenylpentyl}hydrazinocarbonyl)-2,2-dimethylpropyl]carbamic acid methyl ester
  参考文献：
  名称：

  WO2006/84688

  摘要：

  公开号：
• 作为产物：
  描述：

  4-溴苄肼 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 以54%的产率得到{(1S)-1-[N'-(4-bromobenzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}carbamic acid methyl ester
  参考文献：
  名称：

  WO2006/84688

  摘要：

  公开号：

文献信息

• Synthesis of P1′-Functionalized Macrocyclic Transition-State Mimicking HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol
  作者：Maria De Rosa、Johan Unge、Hitesh V. Motwani、Åsa Rosenquist、Lotta Vrang、Hans Wallberg、Mats Larhed

  DOI：10.1021/jm500434q

  日期：2014.8.14

  Seven novel tertiary alcohol containing linear HIV-1 protease inhibitors (PIs), decorated at the para position of the benzyl group in the P1′ side with (hetero)aromatic moieties, were synthesized and biologically evaluated. To study the inhibition and antiviral activity effect of P1–P3 macrocyclization, 14- and 15-membered macrocyclic PIs were prepared by ring-closing metathesis of the corresponding

  合成了七种新颖的含线性HIV-1蛋白酶抑制剂（PIs）的叔醇，它们在P1'侧的苄基对位装饰有（杂）芳族部分，并对其进行了生物学评估。为了研究P1-P3大环化的抑制作用和抗病毒活性，通过相应线性PI的闭环复分解反应制备了14和15元大环PI。大环化合物比线性前体更具活性，化合物10f（在P1'位置带有2-噻唑基）是该新系列中最有效的PI（K i 2.2 nM，EC 50 0.2μM）。制备并分析了线性和大环PI与HIV-1蛋白酶的共结晶复合物。
• Two-Carbon-Elongated HIV-1 Protease Inhibitors with a Tertiary-Alcohol-Containing Transition-State Mimic
  作者：Xiongyu Wu、Per Öhrngren、Jenny K. Ekegren、Johan Unge、Torsten Unge、Hans Wallberg、Bertil Samuelsson、Anders Hallberg、Mats Larhed

  DOI：10.1021/jm070680h

  日期：2008.2.1

  A new generation of HIV-1 protease inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with two carbon atoms and by varying the P1' group of the compounds, efficient inhibitors were obtained with Ki down to 2.3 nM and EC50 down to 0.17 microM. Two inhibitor-enzyme X-ray structures are reported

  已经开发了包含基于叔醇的过渡态模拟物的新一代HIV-1蛋白酶抑制剂。通过延长最近报道的具有两个碳原子的抑制剂的核心结构，并通过改变化合物的P1'基团，可获得有效的抑制剂，其中Ki降至2.3 nM，EC50降至0.17 microM。报道了两种抑制剂-酶的X射线结构。
• Design and Synthesis of P1–P3 Macrocyclic Tertiary-Alcohol-Comprising HIV-1 Protease Inhibitors
  作者：Advait Joshi、Jean-Baptiste Véron、Johan Unge、Åsa Rosenquist、Hans Wallberg、Bertil Samuelsson、Anders Hallberg、Mats Larhed

  DOI：10.1021/jm400811d

  日期：2013.11.27

  tertiary-alcohol-comprising HIV-1 protease inhibitors (PIs), three new 14- and 15-member macrocyclic PIs were designed, synthesized by ring-closing metathesis, and evaluated alongside with 10 novel linear PIs. Cocrystallized complexes of the macrocyclic PIs and the HIV-1 protease are presented, analyzed, and discussed. The macrocyclic structures exhibited higher activities than the linear precursors with

  为了研究先前报道的含叔醇的HIV-1蛋白酶抑制剂（PI）的P1-P3大环化，设计了三个新的14和15元大环PI，通过闭环复分解合成，并与10个新的线性效绩指标。提出，分析和讨论了大环PI和HIV-1蛋白酶的共结晶复合物。大环结构表现出比线性前体更高的活性，K i和EC 50值分别低至3.1 nM和0.37μM。
• Microwave-Accelerated Synthesis of P1‘-Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold
  作者：Jenny K. Ekegren、Nina Ginman、Åsa Johansson、Hans Wallberg、Mats Larhed、Bertil Samuelsson、Torsten Unge、Anders Hallberg

  DOI：10.1021/jm051239z

  日期：2006.3.1

  Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl

  合成了两个系列的P1'延伸的HIV-1蛋白酶抑制剂，它们在过渡态模拟物中包含叔醇，其Ki值在2.1到93 nM之间。微波加速钯催化的交叉偶联用于快速优化P1'侧链。当P1'苄基被3-或4-吡啶基取代基延长时，会遇到高细胞抗病毒效力（EC50 = 0.18-0.22 microM）。获得了与该酶共结晶的三种抑制剂的X射线晶体学数据。
• A New Class of HIV-1 Protease Inhibitors Containing a Tertiary Alcohol in the Transition-State Mimicking Scaffold
  作者：Jenny K. Ekegren、Torsten Unge、Mayada Zreik Safa、Hans Wallberg、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm050790t

  日期：2005.12.1

  Novel HIV-1 protease inhibitors encompassing a tertiary alcohol as part of the transition-state mimicking unit have been synthesized. Variation of the P1'-P3' residues and alteration of the tertiary alcohol absolute stereochemistry afforded 10 inhibitors. High potencies for the compounds with (S)-configuration at the carbon carrying the tertiary hydroxyl group were achieved with Ki values down to 2

  已经合成了包含叔醇作为过渡态模拟单元一部分的新型HIV-1蛋白酶抑制剂。P1'-P3'残基的变化和叔醇绝对立体化学的变化提供了10种抑制剂。在带有叔羟基的碳原子上，具有（S）-构型的化合物具有很高的效能，Ki值低至2.4 nM。给出了与HIV-1蛋白酶复合的代表性化合物的X射线晶体学数据。