(3S)-4-(4-benzyloxy-phenyl)-3-[(4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-1-[(R)-1-phenyl-ethyl]-1,2,3,6-tetrahydro-pyridine | 303043-15-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3S)-4-(4-benzyloxy-phenyl)-3-[(4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-1-[(R)-1-phenyl-ethyl]-1,2,3,6-tetrahydro-pyridine
• 英文别名: (3S)-3-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]-1-[(1R)-1-phenylethyl]-4-(4-phenylmethoxyphenyl)-3,6-dihydro-2H-pyridine
• CAS: 303043-15-4
• 化学式: C₃₂H₃₇NO₄
• 分子量: 499.65
• InChiKey: QVFSJJFHAANXPH-QGXKGNFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S)-4-(4-benzyloxy-phenyl)-3-[(4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-1-[(R)-1-phenyl-ethyl]-1,2,3,6-tetrahydro-pyridine 在 palladium on activated charcoal 吡啶 、 盐酸 、 sodium hydroxide 、 硼烷四氢呋喃络合物 、 氢气 、 sodium methylate 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 81.25h， 生成 (3S,4R,5R)-3-[(2R)-2-hydroxy-3-methoxy-propoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Piperidine renin inhibitors: from leads to drug candidates

  摘要：

  Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalizes albuminuria and kidney tissue damage in these rats when given over a period of 4 weeks. These data suggest that treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status. (C) 2001 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01004-7
• 作为产物：
  描述：

  1,2,3,6-四氢-1-[(1R)-1-苯基乙基]-4-[4-(苯基甲氧基)苯基]吡啶 在 氢溴酸 、 溴 、 sodium hydride 、 苯基锂 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 (3S)-4-(4-benzyloxy-phenyl)-3-[(4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-1-[(R)-1-phenyl-ethyl]-1,2,3,6-tetrahydro-pyridine
  参考文献：
  名称：

  Piperidine renin inhibitors: from leads to drug candidates

  摘要：

  Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalizes albuminuria and kidney tissue damage in these rats when given over a period of 4 weeks. These data suggest that treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status. (C) 2001 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01004-7

文献信息

• Naphthalenylmethoxypiperidines as renin inhibitors
  申请人：Hoffmann-La Roche Inc.

  公开号：US06376672B1

  公开（公告）日：2002-04-23

  The present invention relates to compound of formula (I) wherein R1, R2 and R3 are as defined in the description and claims and pharmaceutically acceptable salts thereof. The compounds are useful for treating diseases associated with restenosis, glaucoma, cardiac infarct, high blood pressure and end organ damage, e.g. cardiac insufficiency and kidney insufficiency.

  本发明涉及式(I)的化合物 式中R1、R2和R3定义如描述和权利要求所述，以及药用可接受的盐。这些化合物用于治疗与再狭窄、青光眼、心肌梗死、高血压和终末器官损伤有关的疾病，例如心功能不全和肾功能不全。
• Naphthalenyl piperidines as renin inhibitors
  申请人：——

  公开号：US20020087002A1

  公开（公告）日：2002-07-04

  Piperidine derivatives, their manufacture and use as medicaments is described. The compounds are useful for treating diseases associated with restenosis, glaucoma, cardiac infarct, high blood pressure and end organ damage, e.g. cardiac insufficiency and kidney insufficiency.

  本文描述了哌啶衍生物的制造和用途作为药物。这些化合物可用于治疗与再狭窄、青光眼、心肌梗塞、高血压和器官损伤相关的疾病，例如心力衰竭和肾功能不全。
• RENIN INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1175400B1

  公开（公告）日：2011-06-15
• US6376672B1
  申请人：——

  公开号：US6376672B1

  公开（公告）日：2002-04-23
• US6673931B2
  申请人：——

  公开号：US6673931B2

  公开（公告）日：2004-01-06