(2S)-1-cyclopropyl-2-isocyanato-3-methylbutan-1-one | 848777-75-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (2S)-1-cyclopropyl-2-isocyanato-3-methylbutan-1-one
• CAS: 848777-75-3
• 化学式: C₉H₁₃NO₂
• 分子量: 167.208
• InChiKey: CCCSNFHITVLMBB-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  46.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,2S,5S)-3-[(2S)-2-amino-3,3-dimethylbutanoyl]-N-[1,2-dioxo-1-(prop-2-enylamino)hexan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide;hydrochloride 、 (2S)-1-cyclopropyl-2-isocyanato-3-methylbutan-1-one 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (1R,5S)-3-[2(S)-[[[[1(S)-(cyclopropylcarbonyl)-2-methylpropyl]amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-N-[1-[1,2-dioxo-2-(propenylamino)ethyl]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2(S)-carboxamide
  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
• 作为产物：
  描述：

  光气 、 (S)-2-amino-1-cyclopropyl-3-methylbutan-1-one hydrochloride 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.5h， 生成 (2S)-1-cyclopropyl-2-isocyanato-3-methylbutan-1-one
  参考文献：
  名称：

  Acylsulfonamide compounds as inhibitors of hepatitis C virus NS3 serine protease

  摘要：

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施例中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。

  公开号：

  US20060046956A1

文献信息

• 3,4-(cyclopentyl)-fused proline compounds as inhibitors of hepatitis C virus NS3 serine protease
  申请人：Njoroge George F.

  公开号：US20050197301A1

  公开（公告）日：2005-09-08

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Discovery and Structure−Activity Relationship of P₁−P₃ Ketoamide Derived Macrocyclic Inhibitors of Hepatitis C Virus NS3 Protease
  作者：Srikanth Venkatraman、Francisco Velazquez、Wanli Wu、Melissa Blackman、Kevin X. Chen、Stephane Bogen、Latha Nair、Xiao Tong、Robert Chase、Andrea Hart、Sony Agrawal、John Pichardo、Andrew Prongay、Kuo-Chi Cheng、Viyyoor Girijavallabhan、John Piwinski、Neng-Yang Shih、F. George Njoroge

  DOI：10.1021/jm800940u

  日期：2009.1.22

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, and affects more than 200 million people worldwide. Although combination therapy of interferon-alpha and ribavirin is reasonably successful in treating 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 a series of ketoamide derived P-1-P-3 macrocyclic inhibitors that are more potent than the first generation clinical candidate, boceprevir (1, Sch 503034), is discussed. The optimization of these macrocyclic inhibitors identified a P-3 imide capped analogue 52 that was 20 times more potent than 1 and demonstrated good oral pharmacokinetics in rats. X-ray structure of 52 bound to NS3 protease and biological data are also discussed.
• 3,4-(CYCLOPENTYL)-FUSED PROLINE COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE
  申请人：Schering Corporation

  公开号：EP1737821B1

  公开（公告）日：2009-08-05
• SUBSTITUTED PROLINES AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE
  申请人：Schering Corporation

  公开号：EP1773868B1

  公开（公告）日：2009-07-15
• Novel inhibitors of Hepatitis C virus NS3 protease
  申请人：Bogen L. Stephane

  公开号：US20070142301A1

  公开（公告）日：2007-06-21

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.