N-isobutyloxycarbonyl(D/L)-tert-leucine | 928758-18-3

• 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: N-isobutyloxycarbonyl(D/L)-tert-leucine
• 英文别名: (2S)-3,3-dimethyl-2-(2-methylpropoxycarbonylamino)butanoic acid
• CAS: 928758-18-3
• 化学式: C₁₁H₂₁NO₄
• 分子量: 231.292
• InChiKey: ITWGKLPBZLSHPT-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-isobutyloxycarbonyl(D/L)-tert-leucine 在 lithium hydroxide 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (3aR,4S,6aR)-5-((S)-2-Isobutoxycarbonylamino-3,3-dimethyl-butyryl)-2,2-dimethyl-hexahydro-furo[2,3-c]pyrrole-4-carboxylic acid
  参考文献：
  名称：

  Discovery of SCH446211 (SCH6):  A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication

  摘要：

  Introduction of various modified prolines at P-2 and optimization of the P-1 side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K-i* = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC50 and IC90 of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

  DOI：

  10.1021/jm060077j

文献信息

• Hepatitis C Inhibitor Compounds
  申请人：LLINAS-BRUNET Montse

  公开号：US20070243166A1

  公开（公告）日：2007-10-18

  Compounds of formula (I): wherein B, X, R 3 , L 0 , L 1 , L 2 , R 2 , R 1 and R C are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  式(I)的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如下。该化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• Discovery of (1<i>R</i>,5<i>S</i>)-<i>N</i>-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(<i>S</i>)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(<i>S</i>)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor:  A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection
  作者：Srikanth Venkatraman、Stéphane L. Bogen、Ashok Arasappan、Frank Bennett、Kevin Chen、Edwin Jao、Yi-Tsung Liu、Raymond Lovey、Siska Hendrata、Yuhua Huang、Weidong Pan、Tejal Parekh、Patrick Pinto、Veljko Popov、Russel Pike、Sumei Ruan、Bama Santhanam、Bancha Vibulbhan、Wanli Wu、Weiying Yang、Jianshe Kong、Xiang Liang、Jesse Wong、Rong Liu、Nancy Butkiewicz、Robert Chase、Andrea Hart、Sony Agrawal、Paul Ingravallo、John Pichardo、Rong Kong、Bahige Baroudy、Bruce Malcolm、Zhuyan Guo、Andrew Prongay、Vincent Madison、Lisa Broske、Xiaoming Cui、Kuo-Chi Cheng、Yunsheng Hsieh、Jean-Marc Brisson、Danial Prelusky、Walter Korfmacher、Ronald White、Susan Bogdanowich-Knipp、Anastasia Pavlovsky、Prudence Bradley、Anil K. Saksena、Ashit Ganguly、John Piwinski、Viyyoor Girijavallabhan、F. George Njoroge

  DOI：10.1021/jm060325b

  日期：2006.10.1

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.
• SAR and pharmacokinetic studies on phenethylamide inhibitors of the hepatitis C virus NS3/NS4A serine protease
  作者：Savina Malancona、Stefania Colarusso、Jesus M Ontoria、Antonella Marchetti、Marco Poma、Ian Stansfield、Ralph Laufer、Annalise Di Marco、Marina Taliani、Maria Verdirame、Odalys Gonzalez-Paz、Victor G Matassa、Frank Narjes

  DOI：10.1016/j.bmcl.2004.05.093

  日期：2004.9

  SAR on the phenethylamide I (K-i 1.2 muM) in the P2- and the V-position led to potent inhibitors, one of which showed good exposure and low clearance when administered intramuscularly to rat. (C) 2004 Elsevier Ltd. All rights reserved.
• US7585845B2
  申请人：——

  公开号：US7585845B2

  公开（公告）日：2009-09-08
• US7939667B2
  申请人：——

  公开号：US7939667B2

  公开（公告）日：2011-05-10