(3S,4R,5S)-5-<<(tertbutyloxy)carbonyl>amino>-6-cyclohexyl-3-hydroxy-4-<(methoxyethoxy)methoxy>hexanenitrile | 122225-18-7

• 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: (3S,4R,5S)-5-<<(tertbutyloxy)carbonyl>amino>-6-cyclohexyl-3-hydroxy-4-<(methoxyethoxy)methoxy>hexanenitrile
• 英文别名: (3S,4R,5S)-5-{[(tertbutyloxy)carbonyl]amino}-6-cyclohexyl-3-hydroxy-4-[(methoxyethoxy)methoxy]hexanenitrile；tert-butyl N-[(2S,3R,4S)-5-cyano-1-cyclohexyl-4-hydroxy-3-(2-methoxyethoxymethoxy)pentan-2-yl]carbamate
• CAS: 122225-18-7
• 化学式: C₂₁H₃₈N₂O₆
• 分子量: 414.543
• InChiKey: YEFVOPZIFCNWRI-GBESFXJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,4R,5S)-5-<<(tertbutyloxy)carbonyl>amino>-6-cyclohexyl-3-hydroxy-4-<(methoxyethoxy)methoxy>hexanenitrile 在 镍 氨 、 氢气 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 (3R,4R,5S)-1-amino-5-<<(tertbutyloxy)carbonyl>amino>-6-cyclohexyl-3-hydroxy-4-<(methoxyethoxy)methoxy>hexane
  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：

  (2RS,3R,4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-3-<(2-methoxyethoxy)methoxy>-1,2-epoxypentane 、 氰化钾 生成 (3S,4R,5S)-5-<<(tertbutyloxy)carbonyl>amino>-6-cyclohexyl-3-hydroxy-4-<(methoxyethoxy)methoxy>hexanenitrile
  参考文献：
  名称：

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

  摘要：

  DOI：

文献信息

• Renin-inhibiting peptidyl heterocycles
  申请人：ABBOTT LABORATORIES

  公开号：EP0307837A2

  公开（公告）日：1989-03-22

  A renin inhibiting compound of the formula: wherein A is a substituent; W is C=O, CHOH or NR₂ wherein R₂ is hydrogen or loweralkyl; U is C=O, CH₂ or NR₂ wherein R₂ is hydrogen or loweralkyl, with the proviso that when W is CHOH then U is CH₂ and with the proviso that U is C=O or CH₂ when W is NR₂; V is CH, C(OH) or C(halogen) with the proviso that V is CH when U is NR₂; R₁ is loweralkyl, cycloalkylalkyl, benzyl, (alpha, alpha)-dimethylbenzyl, 4-methoxybenzyl, halobenzyl, 4-hydroxybenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (unsubstituted heterocyclic)methyl, (substituted heterocyclic)methyl, phenethyl, 1-benzyloxyethyl, phenoxy, thiophenoxy or anilino, provided that B is CH₂ or CHOH or A is hydrogen when R₁ is phenoxy, thiophenoxy or anilino; R₃ is loweralkyl, loweralkenyl, ((alkoxy)alkoxy)alkyl, carboxyalkyl, (thioalkoxy)alkyl, azidoalkyl, aminoalkyl, (alkyl)aminoalkyl, dialkylaminoalkyl, (alkoxy)(alkyl)aminoalkyl, (alkoxy)aminoalkyl, benzyl or heterocyclic ring substituted methyl; R₄ is loweralkyl, cycloalkylmethyl or benzyl; R₅ is OH or NH₂; and Z is a substituent. Also disclosed are compositions for and a method of treating hypertension, methods of making the renin inhibiting compounds and intermediates useful in making the renin inhibiting compounds.

  一种式的肾素抑制化合物： 其中 A 是取代基；W 是 C=O、CHOH 或 NR₂，其中 R₂ 是氢或低级烷基；U 是 C=O、CH₂ 或 NR₂，其中 R₂ 是氢或低级烷基，但当 W 是 CHOH 时，U 是 CH₂，当 W 是 NR₂ 时，U 是 C=O 或 CH₂；V 是 CH、C(OH) 或 C(卤素)，但当 U 是 NR₂ 时，V 是 CH；(取代杂环)甲基、苯乙基、1-苄氧基乙基、苯氧基、噻吩氧基或苯胺基，但当 R₁ 为苯氧基、噻吩氧基或苯胺基时，B 为 CH₂ 或 CHOH 或 A 为氢；R₃ 是低级烷基、低级烯基、((烷氧基)烷氧基)烷基、羧基烷基、(硫代烷氧基)烷基、叠氮烷基、氨基烷基、(烷基)氨基烷基、二烷基氨基烷基、(烷氧基)(烷基)氨基烷基、(烷氧基)氨基烷基、苄基或杂环取代的甲基；R₄ 是低级烷基、环烷基甲基或苄基；R₅ 是 OH 或 NH₂；Z 是取代基。 还公开了治疗高血压的组合物和方法、制造肾素抑制化合物的方法以及制造肾素抑制化合物的中间体。
• Retroviral protease inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0342541A2

  公开（公告）日：1989-11-23

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

  一种抑制逆转录病毒蛋白酶的式化合物： 或其药学上可接受的盐、原药或酯。
• 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.