3-amino-2-hydroxylhexanoic acid hydrochloride | 875628-48-1

• 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
• 英文名称: 3-amino-2-hydroxylhexanoic acid hydrochloride
• 英文别名: (25,35)-3-amino-2-hydroxy-hexanoic acid hydrochloride；3-Amino-2-hydroxyhexanoic acid;hydrochloride
• CAS: 875628-48-1
• 化学式: C₆H₁₃NO₃*ClH
• 分子量: 183.635
• InChiKey: JZKMQEUGSKZJOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.02
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  83.6
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-2-hydroxylhexanoic acid hydrochloride 、 (1R,2S,5S)-3-((S)-2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid 在 N-甲基吗啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-{[(1R,2S,5S)-3-((S)-2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carbonyl]-amino}-2-hydroxy-hexanoic acid
  参考文献：
  名称：

  Discovery of (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-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

  摘要：

  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.

  DOI：

  10.1021/jm060325b
• 作为产物：
  描述：

  2-methyl-4-propyl-4,5-dihydrooxazole-5-carboxylic acid methyl ester 在 盐酸 、 水 作用下， 反应 10.0h， 以100%的产率得到3-amino-2-hydroxylhexanoic acid hydrochloride
  参考文献：
  名称：

  [EN] A METHOD FOR THE PREPARATION OF 3-AMINO-N-CYCLOPROPYL-2-HYDROXYL-HEXANAMIDE
  [FR] PROCÉDÉ DE PRÉPARATION DE 3-AMINO-N-CYCLOPROPYL-2-HYDROXYL-HEXANAMIDE

  摘要：

  本发明公开了一种制备3-氨基-N-环丙基-2-羟基-己酰胺的方法。该发明涉及制药中间体制备技术领域。该方法以反-2-己烯酸为起始原料，通过环氧化、腈的环开、酰胺化等步骤，得到最终产品3-氨基-N-环丙基-2-羟基-己酰胺。该方法使用易得材料，需要温和的反应条件，并采用稳定的工艺。因此适用于大规模工业生产。

  公开号：

  WO2013186248A1

文献信息

• A METHOD FOR THE PREPARATION OF 3-AMINO-N-CYCLOPROPYL-2-HYDROXYL-HEXANAMIDE
  申请人：Janssen Pharmaceutica, N.V.

  公开号：EP2861557A1

  公开（公告）日：2015-04-22
• [EN] A METHOD FOR THE PREPARATION OF 3-AMINO-N-CYCLOPROPYL-2-HYDROXYL-HEXANAMIDE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 3-AMINO-N-CYCLOPROPYL-2-HYDROXYL-HEXANAMIDE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2013186248A1

  公开（公告）日：2013-12-19

  The present invention discloses a method for preparing 3-amino-N-cyclopropyl-2-hydroxyl-hexanamide. The invention relates to the technical field of the preparation of pharmaceutical intermediates. The method uses trans-2-hexenoic acid as the starting material, through the steps of epoxidation, ring-opening by nitrile, amidation, etc., to obtain the final product 3-amino-N-cyclopropyl-2-hydroxyl-hexanamide. The method uses easily-obtainable materials, requires mild reactive conditions, and adopts stable processes. Therefore it is suitable for large scale industrial production.

  本发明公开了一种制备3-氨基-N-环丙基-2-羟基-己酰胺的方法。该发明涉及制药中间体制备技术领域。该方法以反-2-己烯酸为起始原料，通过环氧化、腈的环开、酰胺化等步骤，得到最终产品3-氨基-N-环丙基-2-羟基-己酰胺。该方法使用易得材料，需要温和的反应条件，并采用稳定的工艺。因此适用于大规模工业生产。
• 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.