(33R,35S,91R,92R,5S,E)-5-(叔丁基)-17-甲氧基-4,7-二氧代-2,8- | 1206524-83-5

• 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
• 中文名称: (33R,35S,91R,92R,5S,E)-5-(叔丁基)-17-甲氧基-4,7-二氧代-2,8-
• 英文名称: methyl (1aR,5S,8S,10R,18E,22aR)-5-tert-butyl-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,20,21,22,22a-dodecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxylate
• 英文别名: Methyl (33R,35S,91R,92R,5S,E)-5-(tert-butyl)-17-methoxy-4,7-dioxo-2,8-dioxa-6-aza-1(2,3)-quinoxalina-3(3,1)-pyrrolidina-9(1,2)-cyclopropanacyclotetradecaphan-13-ene-35-carboxylate；methyl (1R,13E,18R,20R,24S,27S)-24-tert-butyl-7-methoxy-22,25-dioxo-2,21-dioxa-4,11,23,26-tetrazapentacyclo[24.2.1.03,12.05,10.018,20]nonacosa-3,5(10),6,8,11,13-hexaene-27-carboxylate
• CAS: 1206524-83-5
• 化学式: C₃₀H₃₈N₄O₇
• 分子量: 566.654
• InChiKey: FECQATNLQHJOIB-IZMSVSEVSA-N

物化性质

• 沸点：
  783.1±60.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  41
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (33R,35S,91R,92R,5S,E)-5-(叔丁基)-17-甲氧基-4,7-二氧代-2,8- 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 水 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 35.0h， 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：

  (S)-3,3-二甲基-2-((((1R,2R)-2-(戊-4-烯-1-基)环丙氧基)羰基)氨基)丁酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 詹氏催化剂 、 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 乙醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (33R,35S,91R,92R,5S,E)-5-(叔丁基)-17-甲氧基-4,7-二氧代-2,8-
  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

• Macrocyclic Quinoxaline Compounds as HCV NS3 Protease Inhibitors
  申请人：Harper Steven

  公开号：US20100029666A1

  公开（公告）日：2010-02-04

  The present invention relates to macrocyclic a compound of formula (I) and its use as inhibitors of the hepatitis C virus (HCV) NS3 protease, and in treating or preventing HCV infections.

  本发明涉及一种具有化学式(I)的大环化合物，以及其作为丙型肝炎病毒（HCV）NS3蛋白酶抑制剂的用途，用于治疗或预防HCV感染。
• MACROCYCLIC QUINOXALINE COMPOUNDS AS HCV NS3 PROTEASE INHIBITORS
  申请人：Harper Steven

  公开号：US20110224134A1

  公开（公告）日：2011-09-15

  The present invention relates to macrocyclic a compound of formula (I) and its use as inhibitors of the hepatitis C virus (HCV) NS3 protease, and in treating or preventing HCV infections.

  本发明涉及一种公式（I）的大环化合物及其用作丙型肝炎病毒（HCV）NS3蛋白酶抑制剂的用途，以及用于治疗或预防HCV感染。
• Macrocyclic quinoxaline compounds as HCV NS3 protease inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07973040B2

  公开（公告）日：2011-07-05

  The present invention relates to macrocyclic a compound of formula (I) and its use as inhibitors of the hepatitis C virus (HCV) NS3 protease, and in treating or preventing HCV infections.

  本发明涉及一种公式（I）的大环化合物及其作为丙型肝炎病毒（HCV）NS3蛋白酶抑制剂的用途，以及用于治疗或预防HCV感染的方法。
• US7973040B2
  申请人：——

  公开号：US7973040B2

  公开（公告）日：2011-07-05
• 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.