(4S,5S)-5-((E)-2-Carboxy-3-methyl-but-1-enyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester | 118586-20-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4S,5S)-5-((E)-2-Carboxy-3-methyl-but-1-enyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester
• 英文别名: 3-[(4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-4-isobutyloxazolidin-5-yl]-2-isopropyl-2-propenoic acid；2-[[(4S,5S)-2,2-dimethyl-4-(2-methylpropyl)-3-phenylmethoxycarbonyl-1,3-oxazolidin-5-yl]methylidene]-3-methylbutanoic acid
• CAS: 118586-20-2
• 化学式: C₂₃H₃₃NO₅
• 分子量: 403.519
• InChiKey: RIQSVQYHVOKXHJ-PMACEKPBSA-N

物化性质

• 沸点：
  533.9±50.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4S,5S)-5-((E)-2-Carboxy-3-methyl-but-1-enyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester 在 钯 叠氮磷酸二苯酯 、 氢气 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Renin Inhibitors. I. Synthesis and Structure-Activity Relationships of Transition-State Inhibitors Containing Homostatine Analogues at the Scissile Bond.

  摘要：

  描述了含有在切割键处的同胺酸类似物的过渡态肾素抑制剂的合成及其结构-活性关系。这些抑制剂包含了与血管紧张素原第7-12位（P4-P2'）相对应的氨基酸侧链。在同胺酸类似物的第2位（P1'）上的乙基、2-羟乙基和3-羟丙基比异丙基更有效地增加了效力。P1、P3和P4位点的氨基酸残基组合对效力很重要，结果表明S1、S3和S4在肾素中共同形成了一个巨大的疏水核心。

  DOI：

  10.1248/cpb.40.364
• 作为产物：
  描述：

  2-(二乙氧基次膦酰基)-3-甲基丁酸乙酯 在 氢氧化钾 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 0.17h， 生成 (4S,5S)-5-((E)-2-Carboxy-3-methyl-but-1-enyl)-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester
  参考文献：
  名称：

  Renin Inhibitors. I. Synthesis and Structure-Activity Relationships of Transition-State Inhibitors Containing Homostatine Analogues at the Scissile Bond.

  摘要：

  描述了含有在切割键处的同胺酸类似物的过渡态肾素抑制剂的合成及其结构-活性关系。这些抑制剂包含了与血管紧张素原第7-12位（P4-P2'）相对应的氨基酸侧链。在同胺酸类似物的第2位（P1'）上的乙基、2-羟乙基和3-羟丙基比异丙基更有效地增加了效力。P1、P3和P4位点的氨基酸残基组合对效力很重要，结果表明S1、S3和S4在肾素中共同形成了一个巨大的疏水核心。

  DOI：

  10.1248/cpb.40.364

文献信息

• 5-substituted amino-4-hydroxy-pentenoic acid derivatives and their use
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US04927565A1

  公开（公告）日：1990-05-22

  A 5-substituted amino-4-hydroxy-pentenoic acid or its salt represented by the formula: ##STR1## wherein each of R.sup.1 and R.sup.2 which may be the same or different is a hydrogen atom, a lower alkyl group, an aralkyl group, a lower alkoxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group or a lower alkanoyl group which may be substituted by from one to three substituents selected from the group consisting of an amino group, a hydroxyl group, a carboxyl group, an aryloxy group, an aralkyloxycarbonylamino group, a lower alkoxycarbonylamino group and a ##STR2## group (wherein each of X.sup.1 and X.sup.2 which may be the same or different is a hydrogen atom, a lower alkyl group, an aryl group or an aralkyl group, or X.sup.1 and X.sup.2 form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may further contain a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom) and which may further contain a double bond in its carbon chain, each of R.sup.3, R.sup.4 and R.sup.6 which may be the same or different is a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an aralkyl group or a residue of an acidic neutral or basic amino acid, R.sup.5 is a hydrogen atom or a lower alkyl group, R.sup.7 is a hydrogen atom, a lower alkyl, cycloalkyl, cycloalkylalkyl or aralkyl group which may be substituted by one or two hydroxyl groups or a residue of an acidic, neutral or basic amino acid, R.sup.8 is a hydroxymethyl group or a --CO--R.sup.9 group (wherein R.sup.9 is a hydroxyl group, a --OY group (wherein Y is a lower alkyl group, an aryl group, an aralkyl group, a lower alkoxyalkyl group, a lower alkanoyloxyalkyl group, a lower alkoxycarbonyloxyalkyl group, or a 1-phthalidyl group) or ##STR3## group (wherein each of Y.sup.1 and Y.sup.2 which may be the same or different is a hydrogen atom, a lower alkyl group, an aryl group, an aralkyl group or a cycloalkyl group, or Y.sup.1 and Y.sup.2 form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may further contain a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom), and each of n and m which may be the same or different is 0 or 1.

  该公式表示的化合物为5-取代氨基-4-羟基-戊烯酸或其盐，其中R1和R2分别为氢原子、低碳基、芳基烷基、低碳氧羰基、芳基氧羰基、芳基烷氧羰基或低碳酰基，可以被选自氨基、羟基、羧基、芳氧基、芳基烷氧羰胺基、低碳氧羰基胺基和##STR2##基团的1-3个取代基所取代；其中X1和X2分别为氢原子、低碳基、芳基或芳基烷基，或X1和X2与相邻氮原子共同形成5-或6-成员杂环基，其可进一步含有来自氮原子、氧原子和硫原子的杂原子；并且还可以在其碳链中进一步含有双键。R3、R4和R6分别为氢原子、低碳基、环烷基、环烷基烷基、芳基、芳基烷基或酸性中性或碱性氨基酸残基；R5为氢原子或低碳基；R7为氢原子、低碳基、环烷基、环烷基烷基或芳基烷基，可以被1或2个羟基取代，或酸性、中性或碱性氨基酸残基；R8为羟甲基或--CO--R9基团（其中R9为羟基、--OY基团（其中Y为低碳基、芳基、芳基烷基、低碳氧烷基、低碳酰氧烷基、低碳氧羰基氧烷基或1-邻苯二甲酰基基团）或##STR3##基团（其中Y1和Y2分别为氢原子、低碳基、芳基、芳基烷基或环烷基，或Y1和Y2与相邻氮原子共同形成5-或6-成员杂环基，其可进一步含有来自氮原子、氧原子和硫原子的杂原子），n和m分别为0或1。
• 5-substituted amino-4-hydroxy-pentanoic acid derivatives and their use
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US04851387A1

  公开（公告）日：1989-07-25

  A 5-substituted amino-4-hydroxy-pentanoic acid derivative having the formula: ##STR1## wherein R.sup.1 is a hydrogen atom or an N-protecting group, R.sup.2, R.sup.3 and R.sup.5 may be any of a variety of groups including the side chains of amino acid residues, R.sup.4 is a hydrogen atom or a lower alkyl group, R.sup.6 is a group which is substituted by one or two hydroxyl groups, and R.sup.7 is any of a variety of groups, including a hydroxyl group, which compounds are renin inhibitors useful as hypotensive drugs, are disclosed.

  公开了一种具有以下式子的5-取代氨基-4-羟基-戊酸衍生物：##STR1## 其中R1是氢原子或N-保护基，R2、R3和R5可以是各种基团，包括氨基酸残基的侧链，R4是氢原子或较低的烷基基团，R6是被一个或两个羟基取代的基团，R7是各种基团，包括羟基，这些化合物是肾素抑制剂，可用作降压药。
• Renin Inhibitors. I. Synthesis and Structure-Activity Relationships of Transition-State Inhibitors Containing Homostatine Analogues at the Scissile Bond.
  作者：Shugo ATSUUMI、Masato NAKANO、Yutaka KOIKE、Seiichi TANAKA、Kenji MATSUYAMA、Makiko NAKANO、Hajime MORISHIMA

  DOI：10.1248/cpb.40.364

  日期：——

  The synthesis and structure-activity relationships of transition-state renin inhibitors containing the homostatine analogues at the scissile bond are described. These inhibitors incorporate the amino acid side chains corresponding to positions 7-12 (P4-P2') of angiotensinogen. Ethyl, 2-hydroxyethyl and 3-hydroxypropyl groups at position 2 of the homostatine analogues (P1') are more effective for increasing potency than the isopropyl group. A combination of residues at P1, P3 and P4 is important for potency and this result auggests that S1, S3 and S4 form a huge hydrophobic core together in renin.

  描述了含有在切割键处的同胺酸类似物的过渡态肾素抑制剂的合成及其结构-活性关系。这些抑制剂包含了与血管紧张素原第7-12位（P4-P2'）相对应的氨基酸侧链。在同胺酸类似物的第2位（P1'）上的乙基、2-羟乙基和3-羟丙基比异丙基更有效地增加了效力。P1、P3和P4位点的氨基酸残基组合对效力很重要，结果表明S1、S3和S4在肾素中共同形成了一个巨大的疏水核心。