2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-indole-6-carboxylic acid methyl ester | 863885-93-2

• 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-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-indole-6-carboxylic acid methyl ester
• 英文别名: methyl 2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxylate；methyl 2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methylindole-6-carboxylate
• CAS: 863885-93-2
• 化学式: C₂₀H₂₀BrN₃O₂
• 分子量: 414.302
• InChiKey: FTFXJPTWZUIUNV-UHFFFAOYSA-N

物化性质

• 沸点：
  482.4±45.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-indole-6-carboxylic acid methyl ester 在 水 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 23.0h， 生成 (E)-3-(2-(1-(2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H-indole-6-carboxamido)cyclobutyl)-1-methyl-1H-benzo[d]imidazol-6-yl)acrylic acid
  参考文献：
  名称：

  Conformation-Based Restrictions and Scaffold Replacements in the Design of Hepatitis C Virus Polymerase Inhibitors: Discovery of Deleobuvir (BI 207127)

  摘要：

  Conformational restrictions of flexible torsion angles were used to guide the identification of new chemotypes of HCV NS5B inhibitors. Sites for rigidification were based on an acquired conformational understanding of compound binding requirements and the roles of substituents in the free and bound states. Chemical bioisosteres of amide bonds were explored to improve cell-based potency. Examples are shown, including the design concept that led to the discovery of the phase III clinical candidate deleobuvir (BI 207127). The structure-based strategies employed have general utility in drug design.

  DOI：

  10.1021/jm4011862
• 作为产物：
  描述：

  5-溴-2-碘嘧啶 在 palladium diacetate 、 三(2-呋喃基)膦 三乙胺 、 频那醇硼烷 、 磷酸 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 40.17h， 以77%的产率得到2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-indole-6-carboxylic acid methyl ester
  参考文献：
  名称：

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

  摘要：

  一个化合物的对映异构体、顺反异构体或互变异构体，由式(I)表示：其中A或B为氮，另一个为B或A为C，基团R1、R2、R3、R4、R5、R6、R7、R8、R9和R10如本文所定义，或其盐或酯作为病毒聚合酶抑制剂。该化合物用作RNA依赖性RNA聚合酶的抑制剂，特别是用于Flaviviridae家族内的病毒聚合酶，更具体地用于HCV聚合酶。

  公开号：

  WO2005080388A1

文献信息

• Process for preparing 2, 3-disubstituted indoles
  申请人：Khodabocus Ahmad

  公开号：US20060183752A1

  公开（公告）日：2006-08-17

  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.

  披露了制备2,3-二取代吲哚化合物的方法，例如通式I所示的化合物，包括以下步骤： a) 在存在配体、钯催化剂和碱的情况下，将溴吲哚化合物(i)与二烷氧基C1-5硼烷反应，制备通式(ii)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在此处定义。
• 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。
• 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
  作者：Pierre L. Beaulieu、Paul C. Anderson、Richard Bethell、Michael Bös、Yves Bousquet、Christian Brochu、Michael G. Cordingley、Gulrez Fazal、Michel Garneau、James R. Gillard、Stephen Kawai、Martin Marquis、Ginette McKercher、Marc-André Poupart、Timothy Stammers、Bounkham Thavonekham、Dominik Wernic、Jianmin Duan、George Kukolj

  DOI：10.1021/jm501532z

  日期：2014.12.11

  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.
• WO2007/19674
  申请人：——

  公开号：——

  公开（公告）日：——