3-amino-2-hydroxy-N-prop-2-enylheptanamide;hydrochloride | 856707-52-3

• 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: 3-amino-2-hydroxy-N-prop-2-enylheptanamide;hydrochloride
• CAS: 856707-52-3
• 化学式: C₁₀H₂₀N₂O₂*ClH
• 分子量: 236.742
• InChiKey: UYZOUDAFFFIMEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.59
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  75.4
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-2-hydroxy-N-prop-2-enylheptanamide;hydrochloride 、 (1R,2S,5S)-3-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyridine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid 在 N-甲基吗啉 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 DMF (N,N-dimethyl-formamide) 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  [EN] INHIBITORS OF HEPATITIS C VIRUS NS3/NS4A SERINE PROTEASE
  [FR] INHIBITEURS DE LA PROTEASE SERINE NS3/NS4A DU VIRUS DE L'HEPATITE C (HCV)

  摘要：

  本发明披露了具有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。在另一实施方案中，本发明披露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：

  WO2005058821A1

文献信息

• [EN] SULFUR COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE<br/>[FR] COMPOSES SOUFRES EN TANT QU'INHIBITEURS DE LA PROTEASE SERINE NS3 DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005087731A1

  公开（公告）日：2005-09-22

  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.

  本发明揭示了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一实施例中，本发明揭示了包含这些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。
• 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。
• Toward Second Generation Hepatitis C Virus NS3 Serine Protease Inhibitors: Discovery of Novel P4 Modified Analogues with Improved Potency and Pharmacokinetic Profile
  作者：Ashok Arasappan、Angela I. Padilla、Edwin Jao、Frank Bennett、Stephane L. Bogen、Kevin X. Chen、Russell E. Pike、Mousumi Sannigrahi、Joana Soares、Srikanth Venkatraman、Bancha Vibulbhan、Anil K. Saksena、Viyyoor Girijavallabhan、Xiao Tong、Kuo-Chi Cheng、F. George Njoroge

  DOI：10.1021/jm801616e

  日期：2009.5.14

  Hepatitis C virus (HCV) infection is a global health crisis leading to liver cirrhosis, hepatocellular carcinoma, and liver failure in humans. Recently, we disclosed the discovery of Boceprevir, SCH 503034 (1), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that is currently undergoing phase III clinical trials. Our efforts toward a second generation HCV NS3 serine protease inhibitor were directed at improving the overall profile of the inhibitor. This article will elaborate on our studies leading to the discovery of new P4 modified inhibitors with enhanced potency and improved oral bioavailability. Thus, introduction of ether and carbamate-derived P4 moieties resulted in improving the replicon potency significantly. Incorporation of the P' secondary amide residue afforded significant improvement in pharmacokinetic properties. Combining the preferred moieties, identified from comprehensive SAR studies, resulted in inhibitors that displayed superior potency and very good oral as well as target organ exposure in rats.
• Towards the second generation of Boceprevir: Dithianes as an alternative P2 substituent for 2,2-dimethyl cycloproyl proline in HCV NS3 protease inhibitors
  作者：Latha G. Nair、Stephane Bogen、Sumei Ruan、Weidong Pan、Russel Pike、Xiao Tong、Kuo-Chi Cheng、Zhuyan Guo、Ronald J. Doll、F. George Njoroge

  DOI：10.1016/j.bmcl.2010.01.037

  日期：2010.3

  Hepatitis C (HCV) infection is a global health crisis leading to chronic liver disease. In our efforts towards a second generation HCV NS3 serine protease inhibitor with improved profile, we have undertaken SAR studies in various regions of Boceprevir including P2. Herein, we report the synthesis and structure-activity relationship studies of inhibitors with (S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid 2 as P2 substituent replacing the (1R,2S,5S)-6,6-dimethyl 3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The systematic investigation led to the discovery of highly potent inhibitor 25 (K-i* = 7 nM, EC90 = 30 nM) with improved rat exposure of 2.56 mu M h. (C) 2010 Published by Elsevier Ltd.
• Synthesis of sterically hindered 3,5,5-trimethyl 2,6-dioxo tetrahydro pyrimidine as HCV protease inhibitors
  作者：Latha G. Nair、Stephane Bogen、Ronald J. Doll、N.-Y. Shih、F. George Njoroge

  DOI：10.1016/j.tetlet.2009.12.129

  日期：2010.3

  An efficient route for the synthesis of sterically hindered substituted and unsubstituted 2,6-dioxo tetra-hydropyrimidines from amine 1 is described. These analogs are active against HCV NS3 serine protease. The biological data for some of the representative examples are also reported. (C) 2009 Elsevier Ltd All rights reserved.