(2R,4S,7S)-7-cyclohexyl-N-((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)-20,23-dimethoxy-12,12-dimethyl-6,9-dioxo-3,4,6,7,8,9,12,13,14,15-decahydro-2H,11H-16,18-(ethanediylidene)-2,5-methanopyrido[4,3-k][1,10,3,6]dioxadiazacyclononadecine-4-carboxamide | 1021436-80-5

• 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
• 英文名称: (2R,4S,7S)-7-cyclohexyl-N-((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)-20,23-dimethoxy-12,12-dimethyl-6,9-dioxo-3,4,6,7,8,9,12,13,14,15-decahydro-2H,11H-16,18-(ethanediylidene)-2,5-methanopyrido[4,3-k][1,10,3,6]dioxadiazacyclononadecine-4-carboxamide
• 英文别名: (3R,5S,8S)-8-cyclohexyl-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-18,22-dimethoxy-13,13-dimethyl-7,10-dioxo-2,11-dioxa-6,9,21-triazatetracyclo[15.6.2.13,6.020,24]hexacosa-1(23),17(25),18,20(24),21-pentaene-5-carboxamide
• CAS: 1021436-80-5
• 化学式: C₄₁H₅₅N₅O₁₀S
• 分子量: 809.981
• InChiKey: UYCGOEJJEOVVPB-AZBSGOJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  57
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  200
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  methyl (2R,4S,7S)-7-cyclohexyl-20,23-dimethoxy-12,12-dimethyl-6,9-dioxo-3,4,6,7,8,9,12,13,14,15-decahydro-2H,11H-16,18-etheno-2,5-methanopyrido[4,3-k][1,10,3,6]dioxadiazacyclononadecine-4-carboxylate 在 HATU 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.58h， 生成 (2R,4S,7S)-7-cyclohexyl-N-((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)-20,23-dimethoxy-12,12-dimethyl-6,9-dioxo-3,4,6,7,8,9,12,13,14,15-decahydro-2H,11H-16,18-(ethanediylidene)-2,5-methanopyrido[4,3-k][1,10,3,6]dioxadiazacyclononadecine-4-carboxamide
  参考文献：
  名称：

  Development of potent macrocyclic inhibitors of genotype 3a HCV NS3/4A protease

  摘要：

  A series of macrocyclic compounds containing 2-substituted-quinoline moieties have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K mutant activity while maintaining the high rat liver exposure. Cyclization of the 2-substituted quinoline substituent led to a series of tricyclic P2 compounds which also display superb gt3a potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.106

文献信息

• HCV NS3 PROTEASE INHIBITORS
  申请人：Liverton Nigel J.

  公开号：US20100093779A1

  公开（公告）日：2010-04-15

  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.

  本发明涉及一种公式（I）的大环化合物，其可用作丙型肝炎病毒（HCV）NS3蛋白酶的抑制剂，其合成以及其用于治疗或预防HCV感染的用途。
• WO2008/51514
  申请人：——

  公开号：——

  公开（公告）日：——
• US8309540B2
  申请人：——

  公开号：US8309540B2

  公开（公告）日：2012-11-13
• [EN] HCV NS3 PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTÉASE NS3 DU HCV
  申请人：MERCK & CO INC

  公开号：WO2008051514A2

  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. (I)
  [FR] La présente invention concerne des composés macrocycliques de formule (I) qui sont utilisables en tant qu'inhibiteurs de la protéase NS3 du virus de l'hépatite C (Hepatitis C Virus : HCV), leur synthèse et leur utilisation pour le traitement ou la prévention des infections par le HCV. (I)
• Development of potent macrocyclic inhibitors of genotype 3a HCV NS3/4A protease
  作者：Michael T. Rudd、John A. McCauley、Joseph J. Romano、John W. Butcher、Kimberly Bush、Charles J. McIntyre、Kevin T. Nguyen、Kevin F. Gilbert、Terry A. Lyle、M. Katharine Holloway、Bang-Lin Wan、Joseph P. Vacca、Vincenzo Summa、Steven Harper、Michael Rowley、Steven S. Carroll、Christine Burlein、Jillian M. DiMuzio、Adam Gates、Donald J. Graham、Qian Huang、Steven W. Ludmerer、Stephanie McClain、Carolyn McHale、Mark Stahlhut、Christine Fandozzi、Anne Taylor、Nicole Trainor、David B. Olsen、Nigel J. Liverton

  DOI：10.1016/j.bmcl.2012.08.106

  日期：2012.12

  A series of macrocyclic compounds containing 2-substituted-quinoline moieties have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K mutant activity while maintaining the high rat liver exposure. Cyclization of the 2-substituted quinoline substituent led to a series of tricyclic P2 compounds which also display superb gt3a potency. (C) 2012 Elsevier Ltd. All rights reserved.