(1R,6R)-6-(4-benzyloxy-phenyl)-3-[(R)-1-phenyl-ethyl]-7-oxa-3-aza-bicyclo [4.1.0] heptane | 257928-40-8

• 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: (1R,6R)-6-(4-benzyloxy-phenyl)-3-[(R)-1-phenyl-ethyl]-7-oxa-3-aza-bicyclo [4.1.0] heptane
• 英文别名: (1R, 6R)-6-(4-benzyloxy-phenyl)-3-[(R)-1-phenyl-ethyl]-7-oxa-3-aza-bicyclo [4.1.0] heptane；(1R,6R)-3-[(1R)-1-phenylethyl]-6-(4-phenylmethoxyphenyl)-7-oxa-3-azabicyclo[4.1.0]heptane
• CAS: 257928-40-8
• 化学式: C₂₆H₂₇NO₂
• 分子量: 385.506
• InChiKey: QDLQLOKAWQCMKV-LIKDZFNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  25
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,6R)-6-(4-benzyloxy-phenyl)-3-[(R)-1-phenyl-ethyl]-7-oxa-3-aza-bicyclo [4.1.0] heptane 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 、 苯基锂 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 84.75h， 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 hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以47%的产率得到(1R,6R)-6-(4-benzyloxy-phenyl)-3-[(R)-1-phenyl-ethyl]-7-oxa-3-aza-bicyclo [4.1.0] heptane
  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

• Process and intermediates for preparation of substituted piperidine-epoxides
  申请人：Hoffman-La Roche Inc.

  公开号：US06268499B1

  公开（公告）日：2001-07-31

  The present invention concerns intermediates useful in and a process for the preparation of a compound of formula 1 or a salt thereof comprisingepoxidation of a compound of formula 2 or a salt thereof wherein A, R1 and R2 are as herein defined. These compounds are useful in the synthesis of renin inhibitors.

  本发明涉及中间体的使用和制备公式1化合物或其盐的过程，包括公式2化合物或其盐的环氧化反应，其中A、R1和R2如本文所定义。这些化合物在肾素抑制剂的合成中有用。
• Process for the preparation of substituted piperidine-epoxides
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0979824B1

  公开（公告）日：2004-10-06
• JP2000063383A
  申请人：——

  公开号：JP2000063383A

  公开（公告）日：2000-02-29
• US6268499B1
  申请人：——

  公开号：US6268499B1

  公开（公告）日：2001-07-31
• 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.