Benzyl 2-isocyanato-2-methylpropanoate | 496057-79-5

• 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-isocyanato-2-methylpropanoate
• CAS: 496057-79-5
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: XLVOMDDRNXDPRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Benzyl 2-isocyanato-2-methylpropanoate 在 palladium on activated charcoal 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (S)-2-(4-(2-((2-(1H-indol-3-yl)ethyl)amino)-2-oxoethyl)-3-(naphthalen-1-ylmethyl)-2,5-dioxoimidazolidin-1-yl)-N-isobutyl-2-methylpropanamide
  参考文献：
  名称：

  基于乙内酰脲的通用肽模拟物的合成和构象分析

  摘要：

  提出了一系列对映体纯的、系统取代的乙内酰脲作为结构优先的通用模拟支架的合成。它依赖于季铵或未取代的 α-氨基酯和N-烷基天冬氨酸二酯的异氰酸酯之间的化学选择性缩合/环化多米诺过程，然后与胺进行标准水解/偶联反应，使用液-液酸/碱萃取方案来纯化中间体。除了异氰酸酯部分上 α 碳的性质（季碳或更灵活的亚甲基）之外，还可以在计算机（分子建模）、溶液中（NMR、圆二色性 (CD)、傅里叶变换红外 (FTIR)）中进行构象研究，并且在固态（X射线）中表明，所提出的基于乙内酰脲的肽模拟物能够将其取代基投射到与常见蛋白质二级结构（例如α-螺旋和β-转角）的侧链重叠的位置，即开放的α根据分子模型，β-螺旋构象稍微有利，而在溶液和固态中优选闭合β-转角构象。

  DOI：

  10.1021/acs.joc.2c01903
• 作为产物：
  描述：

  光气 、 α-氨基异丁酸苄酯 盐酸盐 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 Benzyl 2-isocyanato-2-methylpropanoate
  参考文献：
  名称：

  Toward the Back-Up of Boceprevir (SCH 503034): Discovery of New Extended P₄-Capped Ketoamide Inhibitors of Hepatitis C Virus NS3 Serine Protease with Improved Potency and Pharmacokinetic Profiles

  摘要：

  Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P-4 pocket and optimization of the P-1' capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P-4-capped inhibitors were also found to have improved PK profile.

  DOI：

  10.1021/jm801632a

文献信息

• Toward the Back-Up of Boceprevir (SCH 503034): Discovery of New Extended P₄-Capped Ketoamide Inhibitors of Hepatitis C Virus NS3 Serine Protease with Improved Potency and Pharmacokinetic Profiles
  作者：Stéphane L. Bogen、Weidong Pan、Sumei Ruan、Latha G. Nair、Ashok Arasappan、Frank Bennett、Kevin X. Chen、Edwin Jao、Srikanth Venkatraman、Bancha Vibulbhan、Rong Liu、Kuo-Chi Cheng、Zhuyan Guo、Xiao Tong、Anil K. Saksena、Viyyoor Girijavallabhan、F. George Njoroge

  DOI：10.1021/jm801632a

  日期：2009.6.25

  Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P-4 pocket and optimization of the P-1' capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P-4-capped inhibitors were also found to have improved PK profile.
• Synthesis and Conformational Analysis of Hydantoin-Based Universal Peptidomimetics
  作者：Alessio M. Caramiello、Maria Cristina Bellucci、Gaetano Cristina、Carlo Castellano、Fiorella Meneghetti、Matteo Mori、Francesco Secundo、Fiorenza Viani、Alessandro Sacchetti、Alessandro Volonterio

  DOI：10.1021/acs.joc.2c01903

  日期：——

  The synthesis of a collection of enantiomerically pure, systematically substituted hydantoins as structural privileged universal mimetic scaffolds is presented. It relies on a chemoselective condensation/cyclization domino process between isocyanates of quaternary or unsubstituted α-amino esters and N-alkyl aspartic acid diesters followed by standard hydrolysis/coupling reactions with amines, using

  提出了一系列对映体纯的、系统取代的乙内酰脲作为结构优先的通用模拟支架的合成。它依赖于季铵或未取代的 α-氨基酯和N-烷基天冬氨酸二酯的异氰酸酯之间的化学选择性缩合/环化多米诺过程，然后与胺进行标准水解/偶联反应，使用液-液酸/碱萃取方案来纯化中间体。除了异氰酸酯部分上 α 碳的性质（季碳或更灵活的亚甲基）之外，还可以在计算机（分子建模）、溶液中（NMR、圆二色性 (CD)、傅里叶变换红外 (FTIR)）中进行构象研究，并且在固态（X射线）中表明，所提出的基于乙内酰脲的肽模拟物能够将其取代基投射到与常见蛋白质二级结构（例如α-螺旋和β-转角）的侧链重叠的位置，即开放的α根据分子模型，β-螺旋构象稍微有利，而在溶液和固态中优选闭合β-转角构象。