(S)-3-(5-Carboxymethoxy-1H-indol-3-yl)-2-{(1-[1-cyclohexyl-2-(4-{[2-({1-[4-(1-phenyl-methanoyl)-phenyl]-methanoyl}-amino)-ethylcarbamoyl]-methoxy}-phenyl)-1H-benzoimidazol-5-yl]-methanoyl}-amino)-propionic Acid | 390810-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-3-(5-Carboxymethoxy-1H-indol-3-yl)-2-{(1-[1-cyclohexyl-2-(4-{[2-({1-[4-(1-phenyl-methanoyl)-phenyl]-methanoyl}-amino)-ethylcarbamoyl]-methoxy}-phenyl)-1H-benzoimidazol-5-yl]-methanoyl}-amino)-propionic Acid
• 英文别名: (S)-3-(5-Carboxymethoxy-1H-indol-3-yl)-2-({1-[1-cyclohexyl-2-(4-{[2-({1-[4-(1-phenyl-methanoyl)-phenyl]-methanoyl}-amino)-ethylcarbamoyl]-methoxy}-phenyl)-1H-benzimidazol-5-yl]-methanoyl}-amino)-propionic acid；(2S)-2-[[2-[4-[2-[2-[(4-benzoylbenzoyl)amino]ethylamino]-2-oxo-ethoxy]phenyl]-1-cyclohexyl-benzimidazole-5-carbonyl]amino]-3-[5-(carboxymethyloxy)-1H-indol-3-yl]propanoic acid；(2S)-2-[[2-[4-[2-[2-[(4-benzoylbenzoyl)amino]ethylamino]-2-oxoethoxy]phenyl]-1-cyclohexylbenzimidazole-5-carbonyl]amino]-3-[5-(carboxymethoxy)-1H-indol-3-yl]propanoic acid
• CAS: 390810-32-9
• 化学式: C₅₁H₄₈N₆O₁₀
• 分子量: 904.976
• InChiKey: XDBIXCWKTXNJSY-QLKFWGTOSA-N

物化性质

• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  67
• 可旋转键数：
  19
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  231
• 氢给体数：
  6
• 氢受体数：
  11

文献信息

• Viral polymerase inhibitors
  申请人：——

  公开号：US20020065418A1

  公开（公告）日：2002-05-30

  A compound of the formula I: 1 wherein: X is CH or N; Y is O or S; Z is OH, NH 2 , NMeR 3 , NHR 3 ; OR 3 or 5- or 6-membered heterocycle, having 1 to 4 heteroatoms selected from 0, N and S, said heterocycle being optionally substituted with from 1 to 4 substituents; A is N, COR 7 or CR 5 , wherein R 5 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 R 7 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, (C 2-6 )alkenyl, phenyl(C 2-6 )alkenyl, (C 3-6 )cycloalkyl, (C 1-6 )alkyl, CF 3 , 9- or 10-membered heterobicycle having 1 to 4 heteroatoms selected from O, N and S, wherein said heterocycle, phenyl, phenyl(C 2-6 )alkenyl and phenyl(C 1-3 )alkyl), alkenyl, cycloalkyl, (C 1-6 )alkyl, and heterobicycle are all optionally substituted with from 1 to 4 substituents R 2 is selected from (C 1-6 )alkyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl(C 1-3 )alkyl, (C 6-10 )bicycloalkyl, adamantyl, phenyl, and pyridyl, all of which is optionally substituted with from1 to 4 substituents; R 3 is selected from H, (C 1-6 )alkyl, (C 3-6 )cycloalkyl, (C 3 6 )cycloalkyl(C 1-6 )alkyl, (C 6-10 )aryl, (C 6-10 )aryl(C 1-6 )alkyl, (C 2-6 )alkenyl, (C 3-6 )cycloalkyl(C 2-6 )alkenyl, (C 6-10 )aryl(C 2-6 )alkenyl, N{(C 1-6 )alkyl} 2 , NHCOO(C 1-6 )alkyl(C 6-10 )aryl, NHCO(C 6-10 )aryl, (C 1-6 )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.

  该化合物的结构式为I:1，其中：X为CH或N；Y为O或S；Z为OH、NH2、NMeR3、NHR3、OR3或含有1至4个异原子（0、N和S）的5-或6-成员杂环，该杂环可选择性地与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选自包括含有1至4个异原子（O、N和S）的5-或6-成员杂环、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、含有1至4个异原子（O、N和S）的9-或10-成员杂环的群体，其中该杂环、苯基、苯基（C2-6）烯基和苯基（C1-3）烷基、烯基、环烷基、（C1-6）烷基和杂环均可选择性地与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，所有这些基均可选择性地与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-含有1至4个异原子（O、N和S）的5-或10-原子杂环和含有1至4个异原子（O、N和S）的5-或10-原子杂环；其中所述烷基、环烷基、芳基、烯基和杂环均可选择性地与1至4个取代基取代；n为零或1；或其可检测衍生物或盐。该发明的化合物可用作乙型肝炎病毒复制的抑制剂。该发明还提供了一种治疗或预防乙型肝炎病毒感染的方法。
• Direct binding assay for identifying inhibitors of HCV polymerase
  申请人：Boehringer Ingelheim (Canada) Ltd.

  公开号：US20030108862A1

  公开（公告）日：2003-06-12

  A method for identifying compounds binding to HCV polymerase comprising the steps of:contacting said HCV polymerase or an analog thereof with a probe formula I: 1 wherein A is O, S, N, NR 1 , or CR 1 , wherein R 1 is defined herein; - - - represents either a single or a double bond; R 2 is selected from: H, halogen, R 21 , OR 21 , SR 21 , COOR 21 , SO 2 N(R 22 ) 2 , N(R 22 ) 2 , CON(R 22 ) 2 , NR 22 C(O)R 22 or NR 22 C(O)NR 22 wherein R 21 and each R 22 is defined herein; B is NR 3 or CR 3 , wherein R 3 is defined herein; with the proviso that, when A is not N, then one of A or B is either CR 1 or CR 3 , K is N or CR 4 , wherein R 4 is defined herein; L is N or CR 5 , wherein R 5 has the same definition as R 4 defined above; M is N or CR 7 , wherein R 7 has the same definition as R 4 defined above; R 5 is C(Y 1 )Z wherein Y 1 is O or S; and Z is N(R 6a )R 6 or OR 6 , wherein R 6a is H or alkyl or NR 61 R 62 wherein R 61 and R 62 are defined herein; and R 6 is H, alkyl, cycloalkyl, alkenyl, Het, alkyl-aryl, alkyl-Het; or R 6 is 2 wherein R 7 and R 8 and Q are as defined herein; Y 2 is O or S; R 9 is H, (C 1-6 alkyl), (C 3-7 )cycloalkyl or (C 1-6 )alkyl-(C 3-7 )cycloalkyl, aryl, Het, (C 1-6 )alkyl-aryl or (C 1-6 )alkyl-Het, all of which optionally substituted with R 90 ; or R 9 is covalently bonded to either of R 7 or R 8 to form a 5- or 6-membered heterocycle; or a salt thereof; where the probe comprises a detectable label attached to any suitable position, whereby said probe binds to an HCV polymerase or an analog thereof and is capable of being displaced by an inhibitor thereof.

  一种鉴定与 HCV 聚合酶结合的化合物的方法，包括以下步骤：将所述 HCV 聚合酶或其类似物与探针式 I 接触： 1 其中 A 是 O、S、N、NR 1 或 CR 1 其中 R 1 在此定义； - 代表单键或双键； R 2 选自： H、卤素、R 21 、OR 21 SR 21 , COOR 21 , SO 2 N(R 22 ) 2 ，N(R 22 ) 2 , CON(R 22 ) 2 NR 22 C(O)R 22 或 NR 22 C(O)NR 22 其中 R 21 和每个 R 22 在本文中定义； B 是 NR 3 或 CR 3 其中 R 3 在此定义； 但条件是，当 A 不是 N 时，则 A 或 B 之一为 CR 1 或 CR 3 K 为 N 或 CR 4 其中 R 4 在此定义； L 是 N 或 CR 5 其中 R 5 的定义与 R 4 的定义相同； M 是 N 或 CR 7 ，其中 R 7 的定义与 R 4 的定义相同； R 5 是 C（Y 1 )Z，其中 Y 1 是 O 或 S；以及 Z 是 N(R 6a )R 6 或 OR 6 其中 R 6a 是 H 或烷基或 NR 61 R 62 其中 R 61 和 R 62 在本文中定义；以及 R 6 是 H、烷基、环烷基、烯基、Het、烷基芳基、烷基 Het；或 R 6 是 2 其中 R 7 和 R 8 和 Q 如本文所定义； Y 2 是 O 或 S； R 9 是 H、(C 1-6 烷基）、（C 3-7 环烷基或 (C 1-6 烷基-(C 3-7 )环烷基、芳基、Het、(C 1-6 )烷基芳基或(C 1-6 烷基-芳基或 (C 1-6 )烷基-Het，所有这些均可选择被 R 90 或 R 9 与 R 7 或 R 8 形成 5 或 6 元杂环； 或其盐类；其中探针包括连接在任何适当位置的可检测标记，所述探针据此与 HCV 聚合酶或其类似物结合，并能被其抑制剂置换。
• VIRAL POLYMERASE INHIBITORS
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：EP1301487A2

  公开（公告）日：2003-04-16
• COMPETITIVE BINDING ASSAY FOR IDENTIFYING INHIBITORS OF HCV POLYMERASE
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：EP1417493B1

  公开（公告）日：2010-07-21
• US6448281B1
  申请人：——

  公开号：US6448281B1

  公开（公告）日：2002-09-10