(3R,5S)-3-N-cyclopropyl-5-N-((2R)-1-ethoxy-4-methylpentan-2-yl)-3-N-(5-isopropylpyridin-2-yl)piperidine-3,5-dicarboxamide | 1093954-93-8

• 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: (3R,5S)-3-N-cyclopropyl-5-N-((2R)-1-ethoxy-4-methylpentan-2-yl)-3-N-(5-isopropylpyridin-2-yl)piperidine-3,5-dicarboxamide
• 英文别名: (3S,5R)-5-N-cyclopropyl-3-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-5-N-(5-propan-2-ylpyridin-2-yl)piperidine-3,5-dicarboxamide
• CAS: 1093954-93-8
• 化学式: C₂₆H₄₂N₄O₃
• 分子量: 458.644
• InChiKey: BEFPCHYIIJYUFW-BHDDXSALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,5S)-3-N-cyclopropyl-5-N-((2R)-1-ethoxy-4-methylpentan-2-yl)-3-N-(5-isopropylpyridin-2-yl)piperidine-3,5-dicarboxamide 、 富马酸 以 甲醇 为溶剂， 反应 0.17h， 以97%的产率得到(3R,5S)-3-N-cyclopropyl-5-N-((2R)-1-ethoxy-4-methylpentan-2-yl)-3-N-(5-isopropylpyridin-2-yl)piperidine-3,5-dicarboxamide fumaric 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
• 作为产物：
  描述：

  3,5-吡啶二甲酸 在 盐酸 、 platinum(IV) oxide 、 氯化亚砜 、 N-羟基-7-氮杂苯并三氮唑 、 lithium hydroxide monohydrate 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 氢化奎宁(蒽醌-1,4-二基)二醚 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 乙酸酐 为溶剂， -78.0~80.0 ℃ 、500.01 kPa 条件下， 反应 137.5h， 生成 (3R,5S)-3-N-cyclopropyl-5-N-((2R)-1-ethoxy-4-methylpentan-2-yl)-3-N-(5-isopropylpyridin-2-yl)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

文献信息

• ORGANIC COMPOUNDS
  申请人：Yokokawa Fumiaki

  公开号：US20080319018A1

  公开（公告）日：2008-12-25

  The present invention relates to a compound of the formula I wherein R1, R2, R3, R4 and R5 are as defined in the specification, 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 a compound of that class; a method of treatment comprising administering a compound of that class and a method for its manufacture.

  本发明涉及一种具有以下公式I的化合物，其中R1、R2、R3、R4和R5如规范中所定义，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；该类化合物用于制备用于治疗依赖肾素活性疾病的药物配方；该类化合物用于治疗依赖肾素活性的疾病；该类化合物的药物配方；包括给予该类化合物的治疗方法以及其制造方法。
• US8383650B2
  申请人：——

  公开号：US8383650B2

  公开（公告）日：2013-02-26
• US8497286B2
  申请人：——

  公开号：US8497286B2

  公开（公告）日：2013-07-30