(2RS,3R,4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-3-(methoxymethoxy)-1,2-epoxypentane

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2RS,3R,4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-3-(methoxymethoxy)-1,2-epoxypentane
• 英文别名: (2RS,3R,4S)-3-Methoxymethoxy-4-tert-butyloxycarbonylamino-5-cyclohexyl-1,2-oxopentane；tert-butyl N-[(1R,2S)-3-cyclohexyl-1-(methoxymethoxy)-1-(oxiran-2-yl)propan-2-yl]carbamate
• 化学式: C₁₈H₃₃NO₅
• 分子量: 343.464
• InChiKey: ZYDKVKWJOCPBCD-DLDKDUQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2RS,3R,4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-3-(methoxymethoxy)-1,2-epoxypentane 在 三乙胺 作用下， 以 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 反应 15.5h， 生成 (1'R,2'S,5R)-5-<2'-<<(tertbutyloxy)carbonyl>amino>-3'-cyclohexyl-1'-<(methoxyethoxy)methoxy>propyl>-3-<2-(methylmethoxy)ethyl>oxazolidin-2-one
  参考文献：
  名称：

  Potent, low molecular weight renin inhibitors containing a C-terminal heterocycle: hydrogen bonding at the active site

  摘要：

  A series of low-nanomolar renin inhibitors containing novel C-terminal heterocycles has been designed by formally cyclizing the C-terminus of a glycol-based inhibitor to the second hydroxyl. Molecular modeling suggests that the heterocyclic oxygen hydrogen bonds as an acceptor to the flap region of renin and that the second hydroxyl in the glycol-based inhibitors behaves similarly.

  DOI：

  10.1021/jm00168a009
• 作为产物：
  描述：

  (3S,4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-3-(methoxymethoxy)-1-pentene 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 以1.81 g (95%)的产率得到(2RS,3R,4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-3-(methoxymethoxy)-1,2-epoxypentane
  参考文献：
  名称：

  Renin-inhibiting functionalized peptidyl aminodiols and - triols

  摘要：

  一个公式为的抑制肾素的化合物： 或其药用可接受的盐、酯或前药。

  公开号：

  EP0341602A2

文献信息

• Renin-inhibiting functionalized peptidyl aminodiols and - triols
  申请人：ABBOTT LABORATORIES

  公开号：EP0341602A2

  公开（公告）日：1989-11-15

  A renin inhibiting compound of the formula: or a pharmaceutically acceptable salt, ester or prodrug thereof.

  一个公式为的抑制肾素的化合物： 或其药用可接受的盐、酯或前药。
• ROSENBERG, SAUL H.;WOODS, KEITH W.;KLEINERT, HOLLIS D.;STEIN, HERMAN;NELL+, J. MED. CHEM., 32,(1989) N, C. 1371-1378
  作者：ROSENBERG, SAUL H.、WOODS, KEITH W.、KLEINERT, HOLLIS D.、STEIN, HERMAN、NELL+

  DOI：——

  日期：——
• ROSENBERG, SAUL H.;DELLARIA, JOSEPH F.;KEMPF, DALE J.;HUTCHINS, CHARLES W+, J. MED. CHEM., 33,(1990) N, C. 1582-1590
  作者：ROSENBERG, SAUL H.、DELLARIA, JOSEPH F.、KEMPF, DALE J.、HUTCHINS, CHARLES W+

  DOI：——

  日期：——
• Potent, low molecular weight renin inhibitors containing a C-terminal heterocycle: hydrogen bonding at the active site
  作者：Saul H. Rosenberg、Joseph F. Dellaria、Dale J. Kempf、Charles W. Hutchins、Keith W. Woods、Robert G. Maki、Ed De Lara、Kenneth P. Spina、Herman H. Stein

  DOI：10.1021/jm00168a009

  日期：1990.6

  A series of low-nanomolar renin inhibitors containing novel C-terminal heterocycles has been designed by formally cyclizing the C-terminus of a glycol-based inhibitor to the second hydroxyl. Molecular modeling suggests that the heterocyclic oxygen hydrogen bonds as an acceptor to the flap region of renin and that the second hydroxyl in the glycol-based inhibitors behaves similarly.
• Azido glycols: potent, low molecular weight renin inhibitors containing an unusual post scissile site residue
  作者：Saul H. Rosenberg、Keith W. Woods、Hollis D. Kleinert、Herman Stein、Hugh N. Nellans、Daniel J. Hoffman、Stephen G. Spanton、Richard A. Pyter、Jerome Cohen

  DOI：10.1021/jm00126a038

  日期：1989.6

  Azidomethyl-substituted 1,2- and 1,3-diols were prepared from Boc-cyclohexylalanal and evaluated as transition state analogue renin inhibitors, leading to the development of a small (MW less than 600), nanomolar inhibitor. Remarkable aqueous solubility enhancement followed the incorporation of an N-terminal urea functionality. Evaluation of selected compounds both in vivo and in vitro demonstrated that while transport across the intestine occurred upon id administration, extensive liver extraction resulted in low systemic levels.