(3R)-3-hydroxymethyl-4-{4-[3-(2-methoxybenzyloxy)-propoxy]-phenyl}-5-oxopiperazine-1-carboxylic acid tert-butyl ester | 777934-38-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (3R)-3-hydroxymethyl-4-{4-[3-(2-methoxybenzyloxy)-propoxy]-phenyl}-5-oxopiperazine-1-carboxylic acid tert-butyl ester
• 英文别名: (3R)-3-Hydroxymethyl-4-(4-[3-(2-methoxybenzyloxy)-propoxy]-phenyl)-5-oxo-piperazine-1-carboxylic acid tert-butyl ester；tert-butyl (3R)-3-(hydroxymethyl)-4-[4-[3-[(2-methoxyphenyl)methoxy]propoxy]phenyl]-5-oxopiperazine-1-carboxylate
• CAS: 777934-38-0
• 化学式: C₂₇H₃₆N₂O₇
• 分子量: 500.592
• InChiKey: QYQLBUFAQIYFMM-JOCHJYFZSA-N

物化性质

• 沸点：
  687.9±55.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3R)-3-hydroxymethyl-4-{4-[3-(2-methoxybenzyloxy)-propoxy]-phenyl}-5-oxopiperazine-1-carboxylic acid tert-butyl ester 、 alkaline earth salt of/the/ methylsulfuric acid 在 甲醇 、 15-冠醚-5 、 sodium hydride 、 乙酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (6R)-6-(3,4-difluorobenzyloxymethyl)-1-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperazin-2-one
  参考文献：
  名称：

  Benzyl ether structure–activity relationships in a series of ketopiperazine-based renin inhibitors

  摘要：

  Inhibition of renin enzymatic activity by a series of ketopiperazine-based compounds containing a C6 benzyloxymethyl substituent correlated with a +(pi + sigma) effect. A 3-pyridinyloxymethyl substituent was also found to be equipotent as higher molecular weight analogs, and exhibited decreased CYP3A4 inhibition levels and improved pharmacokinetic properties. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.063
• 作为产物：
  描述：

  3-(2-甲氧基苄氧基)-1-碘丙烷 、 (3R)-3-hydroxymethyl-4-(4-hydroxyphenyl)-5-oxopiperazine-1-carboxylic acid tert-butyl ester 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以89%的产率得到(3R)-3-hydroxymethyl-4-{4-[3-(2-methoxybenzyloxy)-propoxy]-phenyl}-5-oxopiperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] PIPERAZINE DERIVATIVE RENIN INHIBITORS
  [FR] DERIVES DE PIPERAZINE AGISSANT COMME INHIBITEURS DE LA RENINE

  摘要：

  揭示了哌嗪衍生物，它们的制备以及作为肾素抑制剂的用途。化学式（I）：

  公开号：

  WO2004089915A1

文献信息

• Piperazine derivative renin inhibitors
  申请人：——

  公开号：US20040214832A1

  公开（公告）日：2004-10-28

  Disclosed are piperazine derivatives, their manufacture and use as inhibitors of renin.

  本发明涉及哌嗪衍生物，它们的制备和用途作为肾素抑制剂。
• Discovery of novel non-peptidic ketopiperazine-based renin inhibitors
  作者：Daniel D. Holsworth、Noel A. Powell、Dennis M. Downing、Cuiman Cai、Wayne L. Cody、J. Michael Ryan、Robert Ostroski、Mehran Jalaie、John W. Bryant、Jeremy J. Edmunds

  DOI：10.1016/j.bmc.2005.01.048

  日期：2005.4

  Ketopiperazine 2 was designed from a previously published analog. Compound 2 was shown to be a novel, potent inhibitor of renin that, when administered orally, lowered blood pressure in a hypertensive double transgenic (human renin and angiotensinogen) mouse model. Compound 2 was further optimized to sub-nanomolar potency by designing an analog that addressed the S3 sub-pocket of the renin enzyme (16). (c) 2005 Elsevier Ltd. All rights reserved.