(4S)-4-benzyl-3-<(2S,4E)-6-cyclohexyl-2-isopropylhex-4-enoyl>oxazolidin-2-one | 128948-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4S)-4-benzyl-3-<(2S,4E)-6-cyclohexyl-2-isopropylhex-4-enoyl>oxazolidin-2-one
• 英文别名: (4s)-4-benzyl-3-[(2S,4E)-6-cyclohexyl-2-isopropylhex-4-enoyl]oxazolidin-2-one；(4S)-4-benzyl-3-[(E,2S)-6-cyclohexyl-2-propan-2-ylhex-4-enoyl]-1,3-oxazolidin-2-one
• CAS: 128948-72-1
• 化学式: C₂₅H₃₅NO₃
• 分子量: 397.558
• InChiKey: OZPVZVDFZIKVAO-XSOUEMDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S)-4-benzyl-3-<(2S,4E)-6-cyclohexyl-2-isopropylhex-4-enoyl>oxazolidin-2-one 在 palladium on activated charcoal N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 氢气 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 0.17h， 生成 <3S-<3α,5β(R^*)>>-5-(2-Cyclohexyl-1-aminoethyl)dihydro-3-isopropyl-2(3H)-furanone
  参考文献：
  名称：

  使用手性酰基恶唑烷酮的立体选择性溴内酯化有效合成对应于羟乙烯二肽等排物的γ-内酯

  摘要：

  一种有效的合成路线描述于γ内酯对应于二肽电子等排体（2 ，4 ，5 ）-5-氨基-6-环己基-4-羟基-2-异丙基己酸，其中立体化学控制是通过参与实现立体选择性溴内酯化反应中的手性酰基恶唑烷酮。

  DOI：

  10.1016/s0040-4039(01)80674-2
• 作为产物：
  描述：

  1-cyclohexylbut-3-en-2-ol 在 氯化亚砜 、 sodium iodide 、 lithium diisopropyl amide 作用下， 以 乙醚 、 丙酮 为溶剂， 生成 (4S)-4-benzyl-3-<(2S,4E)-6-cyclohexyl-2-isopropylhex-4-enoyl>oxazolidin-2-one
  参考文献：
  名称：

  使用手性酰基恶唑烷酮的立体选择性溴内酯化有效合成对应于羟乙烯二肽等排物的γ-内酯

  摘要：

  一种有效的合成路线描述于γ内酯对应于二肽电子等排体（2 ，4 ，5 ）-5-氨基-6-环己基-4-羟基-2-异丙基己酸，其中立体化学控制是通过参与实现立体选择性溴内酯化反应中的手性酰基恶唑烷酮。

  DOI：

  10.1016/s0040-4039(01)80674-2

文献信息

• Process for the preparation of haloalkyllactones
  申请人：Imperial Chemical Industries PLC

  公开号：US05254697A1

  公开（公告）日：1993-10-19

  The invention provides a novel process for the manufacture of enantiomerically-pure halolactones of the formula I which are useful for the production of certain 5-amino-4-hydroxyvaleric acid derivatives, themselves valuable intermediates in the production of compounds which are renin inhibitors. The process involves a diastereoselective alkylation of an oxazolidinone of the formula III, followed by a highly stereoselective and novel halolactonisation of an oxazolidinone of the formula II. Certain of the oxazolidinones of the formula II are novel and are provided as a further feature of the invention. The invention also provides a novel process for the production of the pharmaceutically-useful 5-amino-4-hydroxyvaleric acid derivatives of formula VI.

  本发明提供了一种制备对映纯卤代内酯（式I）的新工艺，该工艺对于生产某些5-氨基-4-羟基戊酸衍生物非常有用，这些衍生物本身是制备肾素抑制剂化合物的有价值中间体。该工艺涉及到式III的峰异构体烷基化，然后是式II的高度立体选择性和新颖的卤代内酯化反应。其中，某些式II的峰异构体是新颖的，并作为本发明的另一个特征提供。本发明还提供了一种制备具有药用价值的式VI的5-氨基-4-羟基戊酸衍生物的新工艺。
• 1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 2. Synthesis, biological properties and molecular modeling of hydroxyethylene isostere derivatives
  作者：Robert H. Bradbury、John S. Major、Alec A. Oldham、Janet E. Rivett、David A. Roberts、Anthony M. Slater、David Timms、David Waterson

  DOI：10.1021/jm00171a006

  日期：1990.9

  A series of inhibitors of human renin have been synthesized, derived from combination of a 2-(8-propyl-6-pyridin-3-yl-1,2,4-triazolo[4,3-a]pyrazin-3-yl)- 3-pyridin- 3-ylpropionic acid moiety 6c with the hydroxyethylene isostere of the scissile amide bond (2S,4S,5S)-5-amino-6-cyclohexyl-4-hydroxy-2-isopropylhexanoic acid (ChaOH--Val). The more potent members of this series showed good inhibitory activity against partially purified human renin, 7d, for example, having an IC50 of 0.2 nM. Structure-activity relationships for these compounds were consistent with their binding to the S4-S2' sites of human renin. Analogues 7e and 7h-k with a variety of substituents at the C-terminus all had in vitro IC50S less than 1 nM. In contrast with the majority of previously reported inhibitors of similar potency, these compounds contain no natural amino acid fragments. When administered intravenously to anesthetized, sodium-depleted marmosets at doses of 0.3-3.0 mg/kg, compound 7d caused a marked reduction in mean arterial pressure. Following oral administration at 30 mg/kg in the same animal model, 7d again elicited a significant fall in mean arterial pressure, accompanied by suppression of plasma renin activity lasting up to 3 h after dosing.
• BRADBURY, ROBERT H.;REVILL, JOHN M.;RIVETT, JANET E.;WATERSON, DAVID, TETRAHEDRON LETT., 30,(1989) N9, C. 3845-3848
  作者：BRADBURY, ROBERT H.、REVILL, JOHN M.、RIVETT, JANET E.、WATERSON, DAVID

  DOI：——

  日期：——
• BRADBURY, ROBERT H.;MAJOR, JOHN S.;OLDHAM, ALEC A.;RIVETT, JANET E.;ROBER+, J. MED. CHEM., 33,(1990) N, C. 2335-2342
  作者：BRADBURY, ROBERT H.、MAJOR, JOHN S.、OLDHAM, ALEC A.、RIVETT, JANET E.、ROBER+

  DOI：——

  日期：——
• US5254697A
  申请人：——

  公开号：US5254697A

  公开（公告）日：1993-10-19