(2R,4S,7S,14E)-7-cyclohexyl-23-methoxy-4-(methoxycarbonyl)-6-oxo-20-phenyl-3,4,6,7,8,9,10,11,12,13-decahydro-2H-16,18-etheno-2,5-methanopyrido[3,4-r][1,5,8]oxadiazacyclononadecin-8-ium trifluoroacetate | 1000063-84-2

• 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: (2R,4S,7S,14E)-7-cyclohexyl-23-methoxy-4-(methoxycarbonyl)-6-oxo-20-phenyl-3,4,6,7,8,9,10,11,12,13-decahydro-2H-16,18-etheno-2,5-methanopyrido[3,4-r][1,5,8]oxadiazacyclononadecin-8-ium trifluoroacetate
• 英文别名: methyl (3R,5S,8S,15E)-8-cyclohexyl-18-methoxy-7-oxo-22-phenyl-2-oxa-6,9,21-triazatetracyclo[15.6.2.13,6.020,24]hexacosa-1(23),15,17(25),18,20(24),21-hexaene-5-carboxylate;2,2,2-trifluoroacetic acid
• CAS: 1000063-84-2
• 化学式: C₂HF₃O₂*C₃₇H₄₅N₃O₅
• 分子量: 725.805
• InChiKey: KUYZVZDSHAPYCA-UQUDRZPHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.19
• 重原子数：
  52
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (2R,4S,7S,14E)-7-cyclohexyl-23-methoxy-4-(methoxycarbonyl)-6-oxo-20-phenyl-3,4,6,7,8,9,10,11,12,13-decahydro-2H-16,18-etheno-2,5-methanopyrido[3,4-r][1,5,8]oxadiazacyclononadecin-8-ium trifluoroacetate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 (3R,5S,8S,15E)-8-cyclohexyl-18-methoxy-7-oxo-22-phenyl-2-oxa-6,9,21-triazatetracyclo[15.6.2.13,6.020,24]hexacosa-1(23),15,17(25),18,20(24),21-hexaene-5-carboxylic acid
  参考文献：
  名称：

  Inhibitors of the Hepatitis C Virus NS3 Protease with Basic Amine Functionality at the P3-Amino Acid N-Terminus: Discovery and Optimization of a New Series of P2−P4 Macrocycles

  摘要：

  In a follow-Lip to our recent disclosure of P2-P4 macrocyclic inhibitors of the hepatitis C virus (HCV) NS3 protease (e.g., 1, Chart 1), we report a new but related compound series featuring a basic amine at the N-terminus of the P3-amino acid residue. Replacement of the electroneutral P3-amino acid capping group (which is a feature of almost all tripeptide-like inhibitors of NS3 reported to date) with a basic group is not only tolerated but can result in advantageous cell based potency. Optimization of this new class of P3-amine based inhibitors gave compounds such as 25 and 26 that combine excellent cell based activity with pharmacokinetic properties that are attractive for an antiviral targeting HCV.

  DOI：

  10.1021/jm900372w
• 作为产物：
  描述：

  methyl (4R)-1-[(2S)-2-cyclohexyl-2-(hept-6-en-1-ylamino)acetyl]-4-[(7-methoxy-2-phenyl-6-vinylquinolin-4-yl)oxy]-L-prolinate 、 三氟乙酸 在 詹氏钌催化剂-1 作用下， 以 二氯甲烷 为溶剂， 生成 (2R,4S,7S,14E)-7-cyclohexyl-23-methoxy-4-(methoxycarbonyl)-6-oxo-20-phenyl-3,4,6,7,8,9,10,11,12,13-decahydro-2H-16,18-etheno-2,5-methanopyrido[3,4-r][1,5,8]oxadiazacyclononadecin-8-ium trifluoroacetate
  参考文献：
  名称：

  Inhibitors of the Hepatitis C Virus NS3 Protease with Basic Amine Functionality at the P3-Amino Acid N-Terminus: Discovery and Optimization of a New Series of P2−P4 Macrocycles

  摘要：

  In a follow-Lip to our recent disclosure of P2-P4 macrocyclic inhibitors of the hepatitis C virus (HCV) NS3 protease (e.g., 1, Chart 1), we report a new but related compound series featuring a basic amine at the N-terminus of the P3-amino acid residue. Replacement of the electroneutral P3-amino acid capping group (which is a feature of almost all tripeptide-like inhibitors of NS3 reported to date) with a basic group is not only tolerated but can result in advantageous cell based potency. Optimization of this new class of P3-amine based inhibitors gave compounds such as 25 and 26 that combine excellent cell based activity with pharmacokinetic properties that are attractive for an antiviral targeting HCV.

  DOI：

  10.1021/jm900372w

文献信息

• Inhibitors of the Hepatitis C Virus NS3 Protease with Basic Amine Functionality at the P3-Amino Acid N-Terminus: Discovery and Optimization of a New Series of P2−P4 Macrocycles
  作者：Steven Harper、Marco Ferrara、Benedetta Crescenzi、Marco Pompei、Maria Cecilia Palumbi、Jillian M. DiMuzio、Monica Donghi、Fabrizio Fiore、Uwe Koch、Nigel J. Liverton、Silvia Pesci、Alessia Petrocchi、Michael Rowley、Vincenzo Summa、Cristina Gardelli

  DOI：10.1021/jm900372w

  日期：2009.8.13

  In a follow-Lip to our recent disclosure of P2-P4 macrocyclic inhibitors of the hepatitis C virus (HCV) NS3 protease (e.g., 1, Chart 1), we report a new but related compound series featuring a basic amine at the N-terminus of the P3-amino acid residue. Replacement of the electroneutral P3-amino acid capping group (which is a feature of almost all tripeptide-like inhibitors of NS3 reported to date) with a basic group is not only tolerated but can result in advantageous cell based potency. Optimization of this new class of P3-amine based inhibitors gave compounds such as 25 and 26 that combine excellent cell based activity with pharmacokinetic properties that are attractive for an antiviral targeting HCV.