1-(6-Chloro-4-ethoxypyridin-3-yl)ethanone | 1093955-40-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(6-Chloro-4-ethoxypyridin-3-yl)ethanone
• CAS: 1093955-40-8
• 化学式: C₉H₁₀ClNO₂
• 分子量: 199.637
• InChiKey: FUDINEGCYLMTJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(6-Chloro-4-ethoxypyridin-3-yl)ethanone 在 盐酸 、 三乙基硅烷 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 41.0h， 生成 (3R,5S)-3-N-cyclopropyl-5-N-((2R)-1-ethoxy-4-methylpentan-2-yl)-3-N-(4-ethoxy-5-ethylpyridin-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
• 作为产物：
  描述：

  4,6-二羟基烟酸甲酯 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 35.0h， 生成 1-(6-Chloro-4-ethoxypyridin-3-yl)ethanone
  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。
• N5-(2-ETHOXYETHYL)-N3-(2-PYRIDINYL)-3,5-PIPERIDINEDICARBOXAMIDE DERIVATIVES FOR USE AS RENIN INHIBITORS
  申请人：Novartis AG

  公开号：EP2181105B1

  公开（公告）日：2015-04-29
• N5-(2-ETHOXYETHYL)-N3-(2-PYRIDINYL) -3,5-PIPERIDINEDICARBOXAMIDE DERIVATIVES FOR USE AS RENIN INHIBITORS
  申请人：Novartis AG

  公开号：EP2527338B1

  公开（公告）日：2015-05-06
• 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