(3S,5R)-5-[cyclopropyl-[[1-(3-methoxypropyl)indol-3-yl]methyl]carbamoyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid

• 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: (3S,5R)-5-[cyclopropyl-[[1-(3-methoxypropyl)indol-3-yl]methyl]carbamoyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid
• 化学式: C₂₈H₃₉N₃O₆
• 分子量: 513.634
• InChiKey: VHFRMNMSWHKZCF-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,5R)-5-[cyclopropyl-[[1-(3-methoxypropyl)indol-3-yl]methyl]carbamoyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid 在 2,6-二甲基吡啶 、 N-羟基-7-氮杂苯并三氮唑 、 三氟甲磺酸三甲基硅酯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 3-N-cyclopropyl-5-N-isobutyl-3-N-((1-(3-methoxypropyl)-1H-indol-3-yl)methyl)piperidine-3,5-dicarboxamide
  参考文献：
  名称：

  Structure-Based Design of Substituted Piperidines as a New Class of Highly Efficacious Oral Direct Renin Inhibitors

  摘要：

  A cis-configured 3,5-disubstituted piperidine direct renin inhibitor, (syn,rac)-1, was discovered as a high-throughput screening hit from a target-family tailored library. Optimization of both the prime and the nonprime site residues flanking the central piperidine transition-state surrogate resulted in analogues with improved potency and pharmacokinetic (PK) properties, culminating in the identification of the 4-hydroxy-3,5-substituted piperidine 31. This compound showed high in vitro potency toward human renin with excellent off-target selectivity, 60% oral bioavailability in rat, and dose-dependent blood pressure lowering effects in the double-transgenic rat model.

  DOI：

  10.1021/ml500137b
• 作为产物：
  描述：

  3,5-吡啶二甲酸 在 platinum(IV) oxide 、 氯化亚砜 、 氢气 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸酐 为溶剂， 80.0 ℃ 、500.01 kPa 条件下， 反应 128.5h， 生成 (3S,5R)-5-[cyclopropyl-[[1-(3-methoxypropyl)indol-3-yl]methyl]carbamoyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design of Substituted Piperidines as a New Class of Highly Efficacious Oral Direct Renin Inhibitors

  摘要：

  A cis-configured 3,5-disubstituted piperidine direct renin inhibitor, (syn,rac)-1, was discovered as a high-throughput screening hit from a target-family tailored library. Optimization of both the prime and the nonprime site residues flanking the central piperidine transition-state surrogate resulted in analogues with improved potency and pharmacokinetic (PK) properties, culminating in the identification of the 4-hydroxy-3,5-substituted piperidine 31. This compound showed high in vitro potency toward human renin with excellent off-target selectivity, 60% oral bioavailability in rat, and dose-dependent blood pressure lowering effects in the double-transgenic rat model.

  DOI：

  10.1021/ml500137b

文献信息

• Organic Compounds
  申请人：Ehara Takeru

  公开号：US20090192148A1

  公开（公告）日：2009-07-30

  The invention relates to 3,5-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (=disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,5-substituted piperidine compound, and/or a method of treatment comprising administering a 3,5-substituted piperidine compound, a method for the manufacture of a 3,5-substituted piperidine compound, and novel intermediates and partial steps for its synthesis. The compounds have the formula I′ wherein R1, R2, T, R3 and R4 areas defined in the specification.

  本发明涉及3,5-取代哌啶化合物，这些化合物用于诊断和治疗温血动物，特别是用于治疗依赖肾素活性的疾病（=失调）；该类化合物用于制备治疗依赖肾素活性疾病的制剂；该类化合物用于治疗依赖肾素活性的疾病；包括3,5-取代哌啶化合物的制药配方和/或包括给予3,5-取代哌啶化合物的治疗方法，以及制造3,5-取代哌啶化合物的新型中间体和部分合成步骤。该化合物的式子为I'，其中R1、R2、T、R3和R4在规范中有定义。
• 3 , 5-substitued piperidine compounds as renin inhibitors
  申请人：Novartis AG

  公开号：EP2420491A1

  公开（公告）日：2012-02-22

  The invention relates to 3,5-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (= disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,5-substituted piperidine compound, and/or a method of treatment comprising administering a 3,5-substituted piperidine compound, a method for the manufacture of a 3, 5-substituted piperidine compound, and novel intermediates and partial steps for its synthesis. The compounds (which can also be present as salts) have the formula I' wherein R1, R2, T, R3, R4, R7 and R8 are as defined in the specification and R6 is OH.

  本发明涉及3,5-取代的哌啶化合物，这些化合物用于温血动物的诊断和治疗，特别是用于治疗依赖于肾素活性的疾病（=紊乱）；使用该类化合物制备药物制剂，用于治疗依赖于肾素活性的疾病；该类化合物在治疗依赖于肾素活性的疾病中的用途；包含 3,5-取代的哌啶化合物的药物制剂，和/或包括施用 3,5-取代的哌啶化合物的治疗方法，3,5-取代的哌啶化合物的制造方法，及其合成的新型中间体和部分步骤。 这些化合物（也可以以盐的形式存在）具有式 I' 其中 R1、R2、T、R3、R4、R7 和 R8 如说明书中所定义，R6 为 OH。
• WO2007/77005
  申请人：——

  公开号：——

  公开（公告）日：——
• 3 , 5-SUBSTITUED PIPERIDINE COMPOUNDS AS RENIN INHIBITORS
  申请人：Novartis AG

  公开号：EP2420491B1

  公开（公告）日：2013-07-03
• US8129411B2
  申请人：——

  公开号：US8129411B2

  公开（公告）日：2012-03-06