(3R,4R)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol | 257938-64-0

• 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)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol
• 英文别名: (3R,4R)-1-[(1R)-1-phenylethyl]-4-(4-phenylmethoxyphenyl)piperidin-3-ol
• CAS: 257938-64-0
• 化学式: C₂₆H₂₉NO₂
• 分子量: 387.522
• InChiKey: MBWYORJCIZPSQH-VANUSSGQSA-N

物化性质

• 沸点：
  534.9±50.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  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 、 zinc dibromide 作用下， 以 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 127.0h， 生成 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：

  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 硼烷四氢呋喃络合物 、 sodium hydroxide 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以50%的产率得到(3R,4R)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol
  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
• 作为试剂：
  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 、 、 、 sodium hydroxide 、 双氧水 、 氯化钠 在 氩 、 乙酸乙酯 、 水 、 Sodium sulfate-III 、 diastereomeric mixture 、 (3R,4R)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol 作用下， 以 乙酸乙酯 、 乙二醇二甲醚 为溶剂， 反应 26.75h， 以(3S,4S)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol were obtained in a ratio of 3:1的产率得到(3S,4S)-4-(4-benzyloxy-phenyl)-1-((R)-1-phenyl-ethyl)-piperidin-3-ol
  参考文献：
  名称：

  Process and intermediates for preparation of substituted piperidines

  摘要：

  本发明涉及中间体及其制备方法，用于制备公式1化合物或其盐，包括a）对公式2化合物进行氢硼化，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。

  公开号：

  US06274735B1

文献信息

• Process for the production of substituted 3-hydroxypiperidines
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0979819A1

  公开（公告）日：2000-02-16

  The present invention concerns a process for the preparation of a compound of formula 1 or a salt thereof characterised in that the process comprises a) hydroboration of a compound of formula 2 in which formulae A is arylene; R1 is -C*R3R4R5; R2 is -O-alkyl, -O-cycloalkyl, -O-alkenyl, -O-aryl, -O-aralkyl, -O-aralkoxyalkyl, -O-alkylsulfonyl, -O-arylsulfonyl, chlorine, bromine or iodine; R3 is hydrogen; R4 is aryl; R5 is alkyl, cycloalkyl, aryl, alkoxyalkyl or hydroxyalkyl; and wherein C* is an asymmetric carbon atom; b) optionally followed by isolation of the desired stereoisomer.

  本发明涉及一种制备式 1 化合物或其盐的工艺 其特征在于该工艺包括 a) 式 2 化合物的硼氢化反应 其中式 A 为芳基；R1 为-C*R3R4R5；R2 为-O-烷基、-O-环烷基、-O-烯基、-O-芳基、-O-芳烷基、-O-芳烷氧基烷基、-O-烷基磺酰基、-O-芳基磺酰基、氯、溴或碘；R3 为氢；R4 为芳基；R5 为烷基、环烷基、芳基、烷氧基烷基或羟基烷基；且其中 C* 为不对称碳原子； b) 随后可选择分离出所需的立体异构体。
• JP2000063355A
  申请人：——

  公开号：JP2000063355A

  公开（公告）日：2000-02-29
• US6274735B1
  申请人：——

  公开号：US6274735B1

  公开（公告）日：2001-08-14
• Process and intermediates for preparation of substituted piperidines
  申请人：Hoffmann-La Roche Inc.

  公开号：US06274735B1

  公开（公告）日：2001-08-14

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

  本发明涉及在制备化合物1或其盐的过程中有用的中间体和方法，包括a) 对化合物2进行氢硼化反应，其中A、R1和R2如本文所定义。这些化合物在合成肾素抑制剂中很有用。
• 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.