(3R,4R)-3-[1-(2-acetylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester | 304025-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3R,4R)-3-[1-(2-acetylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (3R,4R)-3-[[1-(2-acetamidoethyl)-3,4-dihydro-2H-quinolin-7-yl]methoxy]-4-[4-[3-[(2-methoxyphenyl)methoxy]propoxy]phenyl]piperidine-1-carboxylate
• CAS: 304025-82-9
• 化学式: C₄₁H₅₅N₃O₇
• 分子量: 701.904
• InChiKey: NDUMZDQBNPLOTG-VWMWMKPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  51
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  98.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3R,4R)-3-[1-(2-acetylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester 在 zinc dibromide 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 以71%的产率得到Ro 661168
  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：

  (3R,4R)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 、 sodium hydride 、 sodium carbonate 、 potassium carbonate 、 三乙胺 、 potassium iodide 、 nickel dichloride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 125.0h， 生成 (3R,4R)-3-[1-(2-acetylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-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

文献信息

• Piperidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06197959B1

  公开（公告）日：2001-03-06

  Compounds of formula (I) wherein R1 and R2 are as defined in the description and claims and pharmaceutically acceptable salts thereof, are useful for the treating diseases associated with restenosis, glaucoma, cardiac infarct, high blood pressure and end organ damage, for example, cardiac insufficiency and kidney insufficiency.

  式(I)中的化合物，其中R1和R2如描述和索赔中定义，并且其药学上可接受的盐，对于治疗与再狭窄、青光眼、心脏梗死、高血压和器官损伤相关的疾病是有用的，例如，心脏功能不全和肾功能不全。
• RENIN INHIBITORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1180103B1

  公开（公告）日：2007-05-30
• US6197959B1
  申请人：——

  公开号：US6197959B1

  公开（公告）日：2001-03-06
• [EN] RENIN INHIBITORS<br/>[FR] INHIBITEURS DE LA RENINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000064887A1

  公开（公告）日：2000-11-02

  The present invention relates to compound of formula (I) wherein R?1 and R2¿ are as defined in the description and claims and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment of diseases which are associated restenosis, glaucoma, cardiac infarct, high blood pressure and end organ damage, e.g. cardiac insufficiency and kidney insufficiency.
• Piperidine renin inhibitors: from leads to drug candidates
  作者：H Märki

  DOI：10.1016/s0014-827x(01)01004-7

  日期：2001.3.1

  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.