(3R,5S,8S)-8-cyclohexyl-18-methoxy-13,13-dimethyl-7,10-dioxo-2,11-dioxa-6,9,23-triazatetracyclo[15.6.2.1~3,6~.0~20,24~]hexacosa-1(23),17,19,21,24-pentaene-5-carboxylic acid | 1021435-07-3

• 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: (3R,5S,8S)-8-cyclohexyl-18-methoxy-13,13-dimethyl-7,10-dioxo-2,11-dioxa-6,9,23-triazatetracyclo[15.6.2.1~3,6~.0~20,24~]hexacosa-1(23),17,19,21,24-pentaene-5-carboxylic acid
• 英文别名: (3R,5S,8S)-8-cyclohexyl-18-methoxy-13,13-dimethyl-7,10-dioxo-2,11-dioxa-6,9,23-triazatetracyclo[15.6.2.13,6.020,24]hexacosa-1(23),17,19,21,24-pentaene-5-carboxylic acid
• CAS: 1021435-07-3
• 化学式: C₃₁H₄₁N₃O₇
• 分子量: 567.682
• InChiKey: IWCVCSPIQBOKST-CWDLOFLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  41
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-氨基-N-(环丙基磺酰基)-2-乙烯基-环丙烷羧胺盐酸盐 、 (3R,5S,8S)-8-cyclohexyl-18-methoxy-13,13-dimethyl-7,10-dioxo-2,11-dioxa-6,9,23-triazatetracyclo[15.6.2.1~3,6~.0~20,24~]hexacosa-1(23),17,19,21,24-pentaene-5-carboxylic acid 在 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 N,N-二甲基甲酰胺 为溶剂， 生成 (3R,5S,8S)-8-cyclohexyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-18-methoxy-13,13-dimethyl-7,10-dioxo-2,11-dioxa-6,9,23-triazatetracyclo[15.6.2.13,6.020,24]hexacosa-1(23),17,19,21,24-pentaene-5-carboxamide
  参考文献：
  名称：

  Discovery of MK-1220: A Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease with Improved Preclinical Plasma Exposure

  摘要：

  The discovery of MK-1220 is reported along with the development of a series of HCV NS3/4A protease inhibitors containing a P2 to P4 macrocyclic constraint with improved preclinical pharmacokinetics. Optimization of the P2 heterocycle substitution pattern as well as the P3 amino acid led to compounds with greatly improved plasma exposure following oral dosing in both rats and dogs while maintaining excellent enzyme potency and cellular activity. These studies led to the identification of MK-1220.

  DOI：

  10.1021/ml1002426
• 作为产物：
  描述：

  (2S)-cyclohexyl({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetic acid 在 乙醇 、 palladium on carbon 、 氢气 、 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-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3R,5S,8S)-8-cyclohexyl-18-methoxy-13,13-dimethyl-7,10-dioxo-2,11-dioxa-6,9,23-triazatetracyclo[15.6.2.1~3,6~.0~20,24~]hexacosa-1(23),17,19,21,24-pentaene-5-carboxylic acid
  参考文献：
  名称：

  Discovery of MK-1220: A Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease with Improved Preclinical Plasma Exposure

  摘要：

  The discovery of MK-1220 is reported along with the development of a series of HCV NS3/4A protease inhibitors containing a P2 to P4 macrocyclic constraint with improved preclinical pharmacokinetics. Optimization of the P2 heterocycle substitution pattern as well as the P3 amino acid led to compounds with greatly improved plasma exposure following oral dosing in both rats and dogs while maintaining excellent enzyme potency and cellular activity. These studies led to the identification of MK-1220.

  DOI：

  10.1021/ml1002426

文献信息

• HCV NS3 Protease Inhibitors
  申请人：Liverton Nigel J.

  公开号：US20100317623A1

  公开（公告）日：2010-12-16

  The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

  本发明涉及式（I）的大环化合物，其作为丙型肝炎病毒（HCV）NS3蛋白酶的抑制剂，它们的合成以及它们用于治疗或预防HCV感染的用途。
• WO2008/51475
  申请人：——

  公开号：——

  公开（公告）日：——
• US8138164B2
  申请人：——

  公开号：US8138164B2

  公开（公告）日：2012-03-20
• [EN] HCV NS3 PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTÉASE NS3 DU VHC
  申请人：MERCK & CO INC

  公开号：WO2008051475A2

  公开（公告）日：2008-05-02

  [EN] The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.
  [FR] L'invention concerne des composés macrocycliques de formule (I) qui sont utiles comme inhibiteurs de la protéase NS3 du virus de l'hépatite C (VHC), leur synthèse et leur utilisation dans le traitement ou la prévention d'infections par VHC.
• Discovery of MK-1220: A Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease with Improved Preclinical Plasma Exposure
  作者：Michael T. Rudd、John A. McCauley、John W. Butcher、Joseph J. Romano、Charles J. McIntyre、Kevin T. Nguyen、Kevin F. Gilbert、Kimberly J. Bush、M. Katharine Holloway、John Swestock、Bang-Lin Wan、Steven S. Carroll、Jillian M. DiMuzio、Donald J. Graham、Steven W. Ludmerer、Mark W. Stahlhut、Christine M. Fandozzi、Nicole Trainor、David B. Olsen、Joseph P. Vacca、Nigel J. Liverton

  DOI：10.1021/ml1002426

  日期：2011.3.10

  The discovery of MK-1220 is reported along with the development of a series of HCV NS3/4A protease inhibitors containing a P2 to P4 macrocyclic constraint with improved preclinical pharmacokinetics. Optimization of the P2 heterocycle substitution pattern as well as the P3 amino acid led to compounds with greatly improved plasma exposure following oral dosing in both rats and dogs while maintaining excellent enzyme potency and cellular activity. These studies led to the identification of MK-1220.