methyl N-[oct-7-en-2-yl]-L-valyl-(4R)-4-{[(4-ethenyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinate | 1000063-47-7

• 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: methyl N-[oct-7-en-2-yl]-L-valyl-(4R)-4-{[(4-ethenyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinate
• 英文别名: [(3R,5S)-5-methoxycarbonyl-1-[(2S)-3-methyl-2-(oct-7-en-2-ylamino)butanoyl]pyrrolidin-3-yl] 4-ethenyl-1,3-dihydroisoindole-2-carboxylate
• CAS: 1000063-47-7
• 化学式: C₃₀H₄₃N₃O₅
• 分子量: 525.689
• InChiKey: USYCLPNKCPMUMK-MBIHCMRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl N-[oct-7-en-2-yl]-L-valyl-(4R)-4-{[(4-ethenyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinate 、 三氟乙酸 在 詹氏钌催化剂-1 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 0.67h， 以37%的产率得到(5R,7S,10S,12R,17E)-10-isopropyl-7-(methoxycarbonyl)-12-methyl-3,9-dioxo-6,7,9,10,11,12,13,14,15,16-decahydro-1H,5H-2,22:5,8-dimethano-4,2,8,11-benzoxatriazacycloicosin-11-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