N-[(1S)-2-amino-1-[(5-amino-1H-indol-3-yl)methyl]-2-oxo-ethyl]-1-cyclohexyl-2-(3-furyl)benzimidazole-5-carboxamide

• 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: N-[(1S)-2-amino-1-[(5-amino-1H-indol-3-yl)methyl]-2-oxo-ethyl]-1-cyclohexyl-2-(3-furyl)benzimidazole-5-carboxamide
• 英文别名: N-[(2S)-1-amino-3-(5-amino-1H-indol-3-yl)-1-oxopropan-2-yl]-1-cyclohexyl-2-(furan-3-yl)benzimidazole-5-carboxamide
• 化学式: C₂₉H₃₀N₆O₃
• 分子量: 510.6
• InChiKey: AYBLCTHONWSAOE-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-Nitrotryptophan amide 、 1-环己基-2-(3-呋喃)-1H-苯并咪唑-5-羧酸 、 、 以to give the title compound of example 54的产率得到N-[(1S)-2-amino-1-[(5-amino-1H-indol-3-yl)methyl]-2-oxo-ethyl]-1-cyclohexyl-2-(3-furyl)benzimidazole-5-carboxamide
  参考文献：
  名称：

  Viral polymerase inhibitors

  摘要：

  公式I的化合物：其中：X为CH或N；Y为O或S；Z为OH、NH2、NMeR3、NHR3、OR3或具有1至4个杂原子（O、N和S）的5-或6元杂环，该杂环可选地被1至4个取代基取代；A为N、COR7或CR5，其中R5为H、卤素或（C1-6）烷基，R7为H或（C1-6）烷基，但X和A不能同时为N；R6为H、卤素、（C1-6）烷基或OR7，其中R7为H或（C1-6）烷基；R1选自由有1至4个杂原子（O、N和S）的5-或6元杂环、苯基、苯基（C1-3）烷基、（C2-6）烯基、苯基（C2-6）烯基、（C3-6）环烷基、（C1-6）烷基、CF3、具有1至4个杂原子（O、N和S）的9-或10元杂环，其中所述杂环、苯基、苯基（C2-6）烯基和苯基（C1-3）烷基、烯基、环烷基、（C1-6）烷基和杂环均可选地被1至4个取代基取代；R2选自（C1-6）烷基、（C3-7）环烷基、（C3-7）环烷基（C1-3）烷基、（C6-10）双环烷基、金刚烷基、苯基和吡啶基，所有这些都可选地被1至4个取代基取代；R3选自H、（C1-6）烷基、（C3-6）环烷基、（C3-6）环烷基（C1-6）烷基、（C6-10）芳基（C6-10）芳基（C1-6）烷基、（C2-6）烯基、（C3-6）环烷基（C2-6）烯基、（C6-10）芳基（C2-6）烯基、N{（C1-6）烷基}2、NHCOO（C1-6）烷基（C6-10）芳基、NHCO（C6-10）芳基、（C1-6）烷基-具有1至4个杂原子（O、N和S）的5-或10-元杂环和具有1至4个杂原子（O、N和S）的5-或10-元杂环；其中所述烷基、环烷基、芳基、烯基和杂环均可选地被1至4个取代基取代；n为零或1；或其可检测衍生物或盐。本发明的化合物可用作丙型肝炎病毒复制的抑制剂。本发明还提供了一种治疗或预防丙型肝炎病毒感染的方法。

  公开号：

  US06479508B1

文献信息

• VIRAL POLYMERASE INHIBITORS
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：EP1301487A2

  公开（公告）日：2003-04-16
• US7439258B2
  申请人：——

  公开号：US7439258B2

  公开（公告）日：2008-10-21
• [EN] VIRAL POLYMERASE INHIBITORS<br/>[FR] INHIBITEURS DE POLYMERASE VIRALE
  申请人：BOEHRINGER INGELHEIM CA LTD

  公开号：WO2002004425A2

  公开（公告）日：2002-01-17

  A compound of formula (I) wherein: X is CH or N; Y is O or S; Z is OH, NH2, NMeR?3, NHR3; OR3¿ or 5- or 6-membered heterocycle, having 1 to 4 heteroatoms selected from O, N and S, said heterocycle being optionally substituted with from 1 to 4 substituents; A is N, COR?7 or CR5¿, wherein R5 is H, halogen, or (C¿1-6?) alkyl and R?7¿ is H or (C¿1-6? alkyl), with the proviso that X and A are not both N; R?6¿ is H, halogen, (C¿1-6? alkyl) or OR?7¿, wherein R7 is H or (C¿1-6? alkyl); R?1¿ is selected from the group consisting of 5- or 6-membered heterocycle having 1 to 4 heteroatoms selected from O, N, and S, phenyl, phenyl(C¿1-3?)alkyl, (C2-6)alkenyl, phenyl(C2-6)alkenyl, (C3-6)cycloalkyl, (C1-6)alkyl, CF3, 9- or 10-membered heterobicycle having 1 to 4 heteroatoms selected from O, N and S, wherein said heterocycle, phenyl, phenyl(C2-6)alkenyl and phenyl(C1-3)alkyl, alkenyl , cycloalkyl, (C1-6)alkyl, and heterobicycle are all optionally substituted with from 1 to 4 substituents; R?2¿ is selected from (C¿1-6?)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-3)alkyl, (C6-10)bicycloalkyl, adamantyl, phenyl, and pyridyl, all of which is optionally substituted with from 1 to 4 substituents; R?3¿ is selected from H, (C¿1-6?)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-6)alkyl, (C6-10)aryl, (C6-10)aryl(C1-6)alkyl, (C2-6)alkenyl, (C3-6)cycloalkyl(C2-6)alkenyl, (C6-10)aryl(C2-6)alkenyl, N(C1-6) alkyl}2, NHCOO(C1-6)alkyl(C6-10)aryl, NHCO(C6-10)aryl, (C1-6)alkyl-5- or 10-atom heterocycle, having 1 to 4 heteroatoms selected from O, N and S, and 5- or 10-atom heterocycle having 1 to 4 heteroatoms selected from O, N and S; wherein said alkyl, cycloalkyl, aryl, alkenyl and heterocycle are all optionally substituted with from 1 to 4 substituents; n is zero or 1; or a detectable derivative or salt thereof. The compounds of the invention may be used as inhibitors of hepatitis C virus replication. The invention further provides a method for treating or preventing hepatitis C virus infection.
• Viral polymerase inhibitors
  申请人：Boehringer Ingelheim (Canada) Ltd.

  公开号：US06794404B2

  公开（公告）日：2004-09-21

  A compound of the formula I: wherein: X is CH or N; Y is O or S; Z is OH, NH2, NMeR3, NHR3; OR3 or 5- or 6-membered heterocycle, having 1 to 4 heteroatoms selected from O, N and S, said heterocycle being optionally substituted with from 1 to 4 substituents; A is N, COR7 or CR5, wherein R5 is H, halogen, or (C1-6) alkyl and R7 is H or (C1-6 alkyl), with the proviso that X and A are not both N; R6 is H, halogen, (C1-6 alkyl) or OR7, wherein R7 is H or (C1-6 alkyl); R1 is selected from the group consisting of 5- or 6-membered heterocycle having 1 to 4 heteroatoms selected from O, N, and S, phenyl, phenyl(C1-3)alkyl, (C2-6)alkenyl, phenyl(C2-6)alkenyl, (C3-6)cycloalkyl, (C1-6)alkyl, CF3, 9- or 10-membered heterobicycle having 1 to 4 heteroatoms selected from O, N and S, wherein said heterocycle, phenyl, phenyl(C2-6)alkenyl and phenyl(C1-3)alkyl), alkenyl, cycloalkyl, (C1-6)alkyl, and heterobicycle are all optionally substituted with from 1 to 4 substituents; R2 is selected from (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-3)alkyl, (C6-10)bicycloalkyl, adamantyl, phenyl, and pyridyl, all of which is optionally substituted with from 1 to 4 substituents; R3 is selected from H, (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-6)alkyl, (C6-10)aryl, (C6-10)aryl(C1-6)alkyl, (C2-6)alkenyl, (C3-6)cycloalkyl(C2-6)alkenyl, (C6-10)aryl(C2-6)alkenyl, N{(C1-6) alkyl}2, NHCOO(C1-6)alkyl(C6-10)aryl, NHCO(C6-10)aryl, (C1-6)alkyl-5- or 10-atom heterocycle, having 1 to 4 heteroatoms selected from O, N and S, and 5- or 10-atom heterocycle having 1 to 4 heteroatoms selected from O, N and S; wherein said alkyl, cycloalkyl, aryl, alkenyl and heterocycle are all optionally substituted with from 1 to 4 substituents; n is zero or 1; or a detectable derivative or salt thereof. The compounds of the invention may be used as inhibitors of hepatitis C virus replication. The invention further provides a method for treating or preventing hepatitis C virus infection.

  公式I的化合物：其中：X是CH或N; Y是O或S; Z是OH、NH2、NMeR3、NHR3; OR3或1至4个杂原子选自O、N和S的5-或6元杂环，所述杂环可选择地用1至4个取代基取代; A是N、COR7或CR5，其中R5是H、卤素或（C1-6）烷基，R7是H或（C1-6）烷基，但X和A不能同时为N; R6是H、卤素、（C1-6）烷基或OR7，其中R7是H或（C1-6）烷基; R1选自选自1至4个杂原子选自O、N和S的5-或6元杂环、苯基、苯基（C1-3）烷基、（C2-6）烯基、苯基（C2-6）烯基、（C3-6）环烷基、（C1-6）烷基、CF3、1至4个杂原子选自O、N和S的9-或10元杂环，其中所述杂环、苯基、苯基（C2-6）烯基和苯基（C1-3）烷基）、烯基、环烷基、（C1-6）烷基和杂环都可选择地用1至4个取代基取代; R2选自（C1-6）烷基、（C3-7）环烷基、（C3-7）环烷基（C1-3）烷基、（C6-10）双环烷基、金刚烷基、苯基和吡啶基，所有这些都可以选择地用1至4个取代基取代; R3选自H、（C1-6）烷基、（C3-6）环烷基、（C3-6）环烷基（C1-6）烷基、（C6-10）芳基、（C6-10）芳基（C1-6）烷基、（C2-6）烯基、（C3-6）环烷基（C2-6）烯基、（C6-10）芳基（C2-6）烯基、N（C1-6）烷基2、NHCOO（C1-6）烷基（C6-10）芳基、NHCO（C6-10）芳基、（C1-6）烷基-1至4个杂原子选自O、N和S的5-或10原子杂环，选自O、N和S的1至4个杂原子的5-或10原子杂环;其中所述烷基、环烷基、芳基、烯基和杂环都可以选择地用1至4个取代基取代; n为零或1;或其可检测衍生物或盐。本发明的化合物可用作丙型肝炎病毒复制的抑制剂。本发明还提供了一种治疗或预防丙型肝炎病毒感染的方法。