(3R)-3-hydroxymethyl-4-(4-hydroxyphenyl)-5-oxopiperazine-1-carboxylic acid tert-butyl ester | 777934-43-7

• 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-hydroxyphenyl)-5-oxopiperazine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl (3R)-3-(hydroxymethyl)-4-(4-hydroxyphenyl)-5-oxo-1-piperazinecarboxylate；tert-butyl (3R)-3-(hydroxymethyl)-4-(4-hydroxyphenyl)-5-oxopiperazine-1-carboxylate
• CAS: 777934-43-7
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: UVZIKROBVWNMNB-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R)-3-hydroxymethyl-4-(4-hydroxyphenyl)-5-oxopiperazine-1-carboxylic acid tert-butyl ester 在 偶氮二甲酸二异丙酯 、 polystyrene-PPh₃ 、 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 36.0h， 生成 (3R)-4-{4-[3-(2-methoxybenzyloxy)-propoxy]-phenyl}-3-(naphthalen-2-yloxymethyl)-5-oxopiperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of novel non-peptidic ketopiperazine-based renin inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2005.01.048
• 作为产物：
  描述：

  4-苯甲氧基苯胺盐酸盐 在 palladium dihydroxide sodium hydroxide 、 氢气 、 sodium hydride 、 magnesium sulfate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 50.0 ℃ 、379.21 kPa 条件下， 反应 113.33h， 生成 (3R)-3-hydroxymethyl-4-(4-hydroxyphenyl)-5-oxopiperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Practical Synthesis of 1-Aryl-6-(hydroxymethyl)-2-ketopiperazines via a 6-exo Amide−Epoxide Cyclization

  摘要：

  Chiral 1-aryl-6-(hydroxymethyl)-2-ketopiperazines can be prepared via an operationally simple, 6-exo epoxide ring-opening cyclization to form the ketopiperazine C6-N1 bond in high yields and with excellent enantiomeric purity.

  DOI：

  10.1021/ol048235t

文献信息

• [EN] PIPERAZINE DERIVATIVE RENIN INHIBITORS<br/>[FR] DERIVES DE PIPERAZINE AGISSANT COMME INHIBITEURS DE LA RENINE
  申请人：WARNER LAMBERT CO

  公开号：WO2004089915A1

  公开（公告）日：2004-10-21

  Disclosed are piperazine derivatives, their manufacture and use as inhibitors of renin. Formula (I):

  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）：
• 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.
• Practical Synthesis of 1-Aryl-6-(hydroxymethyl)-2-ketopiperazines via a 6-<i>exo</i> Amide−Epoxide Cyclization
  作者：Noel A. Powell、Fred L. Ciske、Emma C. Clay、Wayne L. Cody、Dennis M. Downing、Peter G. Blazecka、Daniel D. Holsworth、Jeremy J. Edmunds

  DOI：10.1021/ol048235t

  日期：2004.10.1

  Chiral 1-aryl-6-(hydroxymethyl)-2-ketopiperazines can be prepared via an operationally simple, 6-exo epoxide ring-opening cyclization to form the ketopiperazine C6-N1 bond in high yields and with excellent enantiomeric purity.