(2R,4S,7S)-7-cyclopentyl-4-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-6-oxo-3,4,6,7,8,9,10,11,12,13,14,15-dodecahydro-2H-16,18-etheno-2,5-methanopyrido[3,2-r][1,5,8]oxadiazacyclononadecin-8-ium trifluoroacetate | 1179842-44-4

• 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)-7-cyclopentyl-4-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-6-oxo-3,4,6,7,8,9,10,11,12,13,14,15-dodecahydro-2H-16,18-etheno-2,5-methanopyrido[3,2-r][1,5,8]oxadiazacyclononadecin-8-ium trifluoroacetate
• 英文别名: (3R,5S,8S)-8-cyclopentyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-7-oxo-2-oxa-6,9,23-triazatetracyclo[15.6.2.13,6.020,24]hexacosa-1(23),17(25),18,20(24),21-pentaene-5-carboxamide;2,2,2-trifluoroacetic acid
• CAS: 1179842-44-4
• 化学式: C₂HF₃O₂*C₃₇H₄₉N₅O₆S
• 分子量: 805.916
• InChiKey: JIPNTOBQJHEFBS-NQWJEEMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  56
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  193
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  (3R,5S,8S)-8-cyclopentyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-7-oxo-2-oxa-6,9,23-triazatetracyclo[15.6.2.13,6.020,24]hexacosa-1(23),17(25),18,20(24),21-pentaene-5-carboxamide 、 三氟乙酸 以 水 、 乙腈 为溶剂， 以140 mg的产率得到(2R,4S,7S)-7-cyclopentyl-4-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-6-oxo-3,4,6,7,8,9,10,11,12,13,14,15-dodecahydro-2H-16,18-etheno-2,5-methanopyrido[3,2-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