trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane
• 英文别名: trimethyl-[(1R,2R)-2-pent-4-enylcyclopropyl]oxysilane
• 化学式: C₁₁H₂₂OSi
• 分子量: 198.381
• InChiKey: YRMKWXRKLOZRHT-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.58
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane 在 吡啶 、 4-二甲氨基吡啶 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 lithium hydroxide monohydrate 、 詹氏催化剂 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 水 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 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 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 47.0h， 生成 格佐匹韦
  参考文献：
  名称：

  Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor

  摘要：

  A new class of HCV NS3/4a protease inhibitors containing a P2 to P4 macrocyclic constraint was designed using a molecular modeling-derived strategy. Building on the profile of previous clinical compounds and exploring the P2 and linker regions of the series allowed for optimization of broad genotype and mutant enzyme potency, cellular activity, and rat liver exposure following oral dosing. These studies led to the identification of clinical candidate 15 (MK-5172), which is active against genotype 1-3 NS3/4a and clinically relevant mutant enzymes and has good plasma exposure and excellent liver exposure in multiple species.

  DOI：

  10.1021/ml300017p
• 作为产物：
  描述：

  二碘甲烷 、 (E)-1-trimethylsilyloxy-1,6-heptadiene 在 diethylzinc 、 吡啶 作用下， 以 正己烷 、 甲苯 为溶剂， 反应 0.25h， 生成 trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane
  参考文献：
  名称：

  Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor

  摘要：

  A new class of HCV NS3/4a protease inhibitors containing a P2 to P4 macrocyclic constraint was designed using a molecular modeling-derived strategy. Building on the profile of previous clinical compounds and exploring the P2 and linker regions of the series allowed for optimization of broad genotype and mutant enzyme potency, cellular activity, and rat liver exposure following oral dosing. These studies led to the identification of clinical candidate 15 (MK-5172), which is active against genotype 1-3 NS3/4a and clinically relevant mutant enzymes and has good plasma exposure and excellent liver exposure in multiple species.

  DOI：

  10.1021/ml300017p

文献信息

• Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor
  作者：Steven Harper、John A. McCauley、Michael T. Rudd、Marco Ferrara、Marcello DiFilippo、Benedetta Crescenzi、Uwe Koch、Alessia Petrocchi、M. Katharine Holloway、John W. Butcher、Joseph J. Romano、Kimberly J. Bush、Kevin F. Gilbert、Charles J. McIntyre、Kevin T. Nguyen、Emanuela Nizi、Steven S. Carroll、Steven W. Ludmerer、Christine Burlein、Jillian M. DiMuzio、Donald J. Graham、Carolyn M. McHale、Mark W. Stahlhut、David B. Olsen、Edith Monteagudo、Simona Cianetti、Claudio Giuliano、Vincenzo Pucci、Nicole Trainor、Christine M. Fandozzi、Michael Rowley、Paul J. Coleman、Joseph P. Vacca、Vincenzo Summa、Nigel J. Liverton

  DOI：10.1021/ml300017p

  日期：2012.4.12

  A new class of HCV NS3/4a protease inhibitors containing a P2 to P4 macrocyclic constraint was designed using a molecular modeling-derived strategy. Building on the profile of previous clinical compounds and exploring the P2 and linker regions of the series allowed for optimization of broad genotype and mutant enzyme potency, cellular activity, and rat liver exposure following oral dosing. These studies led to the identification of clinical candidate 15 (MK-5172), which is active against genotype 1-3 NS3/4a and clinically relevant mutant enzymes and has good plasma exposure and excellent liver exposure in multiple species.