{(1S)-1-cyclohexyl-2-[(2S,4R)-2-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-4-({7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl}oxy)pyrrolidin-1-yl]-2-oxoethyl}carbamate | 1179842-88-6

• 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: {(1S)-1-cyclohexyl-2-[(2S,4R)-2-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-4-({7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl}oxy)pyrrolidin-1-yl]-2-oxoethyl}carbamate
• 英文别名: tert-butyl N-[(1S)-1-cyclohexyl-2-[(2S,4R)-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-4-[7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl]oxypyrrolidin-1-yl]-2-oxoethyl]carbamate
• CAS: 1179842-88-6
• 化学式: C₄₃H₅₇N₇O₉S₂
• 分子量: 880.099
• InChiKey: MLGNMAPUTSDKHI-CUIYCDBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  61
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  244
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  {(1S)-1-cyclohexyl-2-[(2S,4R)-2-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-4-({7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl}oxy)pyrrolidin-1-yl]-2-oxoethyl}carbamate 、 三氟乙酸 以 水 、 乙腈 为溶剂， 以100 mg的产率得到tert-butyl {(1S)-1-cyclohexyl-2-[(2S,4R)-2-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-4-({7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl}oxy)pyrrolidin-1-yl]-2-oxoethyl}carbamate 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
• 作为产物：
  描述：

  (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide 、 在 4-二甲氨基吡啶 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.08h， 生成 {(1S)-1-cyclohexyl-2-[(2S,4R)-2-({(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)-4-({7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl}oxy)pyrrolidin-1-yl]-2-oxoethyl}carbamate
  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