| 1534367-66-2

• 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
• CAS: 1534367-66-2
• 化学式: C₄₂H₅₈N₄O₉
• 分子量: 762.944
• InChiKey: BHNVJVFMRLBTGT-BVNNMLJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.71
• 重原子数：
  55.0
• 可旋转键数：
  4.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  145.83
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  在 lithium hydroxide monohydrate 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 tert-butyl 4-{[(1aR,5S,8S,10R,22aR)-5-cyclohexyl-8-{[(1R,2S)-2-ethenyl-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]carbamoyl}-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinolin-17-yl]oxy}piperidine-1-carboxylate
  参考文献：
  名称：

  Novel Quinoline-Based P2–P4 Macrocyclic Derivatives As Pan-Genotypic HCV NS3/4a Protease Inhibitors

  摘要：

  We have previously reported the discovery of our P2-P4 macrocyclic HCV NS3/4a protease inhibitor MK-5172, which in combination with the NS5a inhibitor MK-8742 recently received a breakthrough therapy designation from the US FDA for treatment of chronic HCV infection. Our goal for the next generation NS3/4a inhibitor was to achieve pan-genotypic activity while retaining the pharmacokinetic profile of MK-5172. One of the areas for follow-up investigation involved replacement of the quinoxaline moiety in MK-5172 with a quinoline and studying the effect of substitution at 4-position of the quinoline. The rationale for this effort was based on molecular modeling, which indicated that such modifications would improve interactions with the S2 subsite, in particular with D79. We wish to report herein the discovery of highly potent inhibitors with pan-genotypic activity and an improved profile over MK-5172, especially against gt-3a and A156 mutants.

  DOI：

  10.1021/ml400466p
• 作为产物：
  描述：

  (1R,2R)-2-(4-戊炔-1-基)环丙醇 在 双(乙腈)氯化钯(II) 、 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 tri tert-butylphosphoniumtetrafluoroborate 、 二苄胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 75.0 ℃ 、101.33 kPa 条件下， 反应 25.0h， 生成
  参考文献：
  名称：

  Novel Quinoline-Based P2–P4 Macrocyclic Derivatives As Pan-Genotypic HCV NS3/4a Protease Inhibitors

  摘要：

  We have previously reported the discovery of our P2-P4 macrocyclic HCV NS3/4a protease inhibitor MK-5172, which in combination with the NS5a inhibitor MK-8742 recently received a breakthrough therapy designation from the US FDA for treatment of chronic HCV infection. Our goal for the next generation NS3/4a inhibitor was to achieve pan-genotypic activity while retaining the pharmacokinetic profile of MK-5172. One of the areas for follow-up investigation involved replacement of the quinoxaline moiety in MK-5172 with a quinoline and studying the effect of substitution at 4-position of the quinoline. The rationale for this effort was based on molecular modeling, which indicated that such modifications would improve interactions with the S2 subsite, in particular with D79. We wish to report herein the discovery of highly potent inhibitors with pan-genotypic activity and an improved profile over MK-5172, especially against gt-3a and A156 mutants.

  DOI：

  10.1021/ml400466p