2-(5-chloropyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxylic acid | 905856-75-9

• 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: 2-(5-chloropyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxylic acid
• 英文别名: 2-(5-Chloropyrimidin-2-yl)-3-cyclopentyl-1-methylindole-6-carboxylic acid
• CAS: 905856-75-9
• 化学式: C₁₉H₁₈ClN₃O₂
• 分子量: 355.824
• InChiKey: LDSKENSEJAAYOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(5-chloropyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxylic acid 在 乙酸酐 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 1.05h， 生成
  参考文献：
  名称：

  Discovery of BI 207524, an Indole Diamide NS5B Thumb Pocket 1 Inhibitor with Improved Potency for the Potential Treatment of Chronic Hepatitis C Virus Infection

  摘要：

  The development of interferon-free regimens for the treatment of chronic HCV infection constitutes a preferred option that is expected in the future to provide patients with improved efficacy, better tolerability, and reduced risk for emergence of drug-resistant virus. We have pursued non-nucleoside NS5B polymerase allosteric inhibitors as combination partners with other direct acting antivirals (DAAs) having a complementary mechanism of action. Herein, we describe the discovery of a potent follow-up compound (BI 207524, 27) to the first thumb pocket 1 NS5B inhibitor to demonstrate antiviral activity in genotype 1 HCV infected patients, BILB 1941 (1). Cell-based replicon potency was significantly improved through electronic modulation of the pKa of the carboxylic acid function of the lead molecule. Subsequent ADME-PK optimization lead to 27, a predicted low clearance compound in man. The preclinical profile of inhibitor 27 is discussed, as well as the identification of a genotoxic metabolite that led to the discontinuation of the development of this compound.

  DOI：

  10.1021/jm501532z
• 作为产物：
  描述：

  Methyl 2-(5-chloropyrimidin-2-yl)-3-cyclopentyl-1-methylindole-6-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 生成 2-(5-chloropyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxylic acid
  参考文献：
  名称：

  [EN] VIRAL POLYMERASE INHIBITORS
  [FR] INHIBITEURS DE LA POLYMERASE VIRALE

  摘要：

  一种化合物，由化学式(I)表示，或其对映体、顺反异构体或互变异构体：其中A或B是氮，另一个是B或A是C，基团R1、R2、R3、R5、R6、R7、R9和R10如本文所定义，或其盐、酯或衍生物作为病毒聚合酶抑制剂。该化合物被用作RNA依赖性RNA聚合酶的抑制剂，特别是在黄病毒科家族中的病毒聚合酶，更具体地说是HCV聚合酶。

  公开号：

  WO2006007693A1

文献信息

• Viral polymerase inhibitors
  申请人：Beaulieu Pierre

  公开号：US20060052418A1

  公开（公告）日：2006-03-09

  A compound, represented by formula (I): wherein A, B, R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 9 , and R 10 are as defined herein, or an enantiomer, diastereoisomer or tautomer thereof, including a salt, ester or derivative thereof, as an inhibitor of HCV NS5B polymerase.

  化合物的化学式为（I）：其中A，B，R1，R2，R3，R5，R6，R7，R9和R10的定义如本文所述，或其对映异构体，顺反异构体或互变异构体，包括其盐，酯或衍生物，作为HCV NS5B聚合酶的抑制剂。
• Viral Polymerase Inhibitors
  申请人：BEAULIEU Pierre

  公开号：US20070249629A1

  公开（公告）日：2007-10-25

  A compound, represented by formula (I): wherein A, B, R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 9 , and R 10 are as defined herein, or an enantiomer, diastereoisomer or tautomer thereof, including a salt, ester or derivative thereof, as an inhibitor of HCV NS5B polymerase.

  一种化合物，用公式(I)表示：其中A，B，R1，R2，R3，R5，R6，R7，R9和R10如本文所定义，或其对映异构体、顺反异构体或互变异构体，包括其盐、酯或衍生物，作为HCV NS5B聚合酶的抑制剂。
• PROCESS FOR PREPARING 2,3-DISUBSTITUTED INDOLES
  申请人：KHODABOCUS Ahmad

  公开号：US20090264655A1

  公开（公告）日：2009-10-22

  Disclosed are processes for making 2, 3 disubstituted indole compounds such as compounds of general formula I comprised of the steps of a) reacting a bromoindole compound (i) with a dialkoxyl C 1-5 borane in the presence of a ligand, a palladium catalyst and a base to make a compound of general formula (ii); or alternatively reacting compound (i) with a trialkyl magnesiate reagent, followed by treatment with a borate; b) reacting the product of step a with a R2-Hal where R2-Hal is defined herein.

  公开了制备2,3-二取代吲哚化合物的方法，例如由公式I组成的化合物，包括以下步骤：a)在配体、钯催化剂和碱的存在下，将溴吲哚化合物（i）与二烷氧基C1-5硼烷反应，制备公式（ii）的化合物；或者将化合物（i）与三烷基镁试剂反应，然后用硼酸盐处理；b)将步骤a的产物与R2-Hal反应，其中R2-Hal的定义如本文所述。
• Process for preparing 2, 3-disubstituted indoles
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2530082A1

  公开（公告）日：2012-12-05

  Disclosed are processes for making 2, 3 disubstituted indole compounds such as compounds of general formula I comprised of the steps of a) reacting a bromoindole compound (i) with a dialkoxyl C1-5 borane in the presence of a ligand, a palladium catalyst and a base to make a compound of general formula (ii); or alternatively reacting compound (i) with a trialkyl magnesiate reagent, followed by treatment with a borate; b) reacting the product of step a with a R2-Hal where R2-Hal is defined herein.

  本发明公开了制造 2、3 二取代吲哚化合物（如通式 I 的化合物）的工艺，包括以下步骤 a) 在配体、钯催化剂和碱存在下，使溴吲哚化合物(i)与二烷氧基 C1-5 硼烷反应，生成通式(ii)化合物；或者使化合物(i)与三烷基镁酸盐试剂反应，然后用硼酸盐处理； b) 将步骤 a 的产物与 R2-Hal 反应，其中 R2-Hal 在此定义。
• WO2007/19674
  申请人：——

  公开号：——

  公开（公告）日：——