N-{4-[(S)-2,5-Dioxo-2-(4-phenyl-butyl)-2λ5-[1,3,2]dioxaphospholan-4-yl]-butyl}-2,2,2-trifluoro-acetamide | 126111-23-7

• 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: N-{4-[(S)-2,5-Dioxo-2-(4-phenyl-butyl)-2λ5-[1,3,2]dioxaphospholan-4-yl]-butyl}-2,2,2-trifluoro-acetamide
• CAS: 126111-23-7
• 化学式: C₁₈H₂₃F₃NO₅P
• 分子量: 421.353
• InChiKey: PCWOFYIRCOJQGC-GKIKDSKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-{4-[(S)-2,5-Dioxo-2-(4-phenyl-butyl)-2λ5-[1,3,2]dioxaphospholan-4-yl]-butyl}-2,2,2-trifluoro-acetamide 在 lithium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 6.5h， 生成 Lithium; (2S,4S)-1-{(S)-6-amino-2-[hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-hexanoyl}-4-phenylsulfanyl-pyrrolidine-2-carboxylate
  参考文献：
  名称：

  (Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme. 2. Terminal amino acid analogs of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline

  摘要：

  Analogues of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and evaluated as inhibitors of angiotensin converting enzyme in vitro and in vivo. In general, the addition of lipophilic substituents to the 4-position of proline of the parent phosphonate 1 resulted in substantial increases in in vitro activity. The largest improvements were observed in the case of cis-benzyl (36-fold) and dithioketal (24-fold) analogues 2r and 2x, respectively. These enhancements of in vitro activity were accompanied by modest increases (2-3.5-fold) in in vivo (iv) activity. Among the various terminal amino acid replacements examined in this study, the indoline-based analogue 2i was by far the most potent compound on iv administration in the normotensive rat.

  DOI：

  10.1021/jm00167a028
• 作为产物：
  描述：

  (S)-2-<oxy>-6-<(trifluoroacetyl)amino>hexanoic acid 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 N-{4-[(S)-2,5-Dioxo-2-(4-phenyl-butyl)-2λ5-[1,3,2]dioxaphospholan-4-yl]-butyl}-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  (Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme. 2. Terminal amino acid analogs of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline

  摘要：

  Analogues of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and evaluated as inhibitors of angiotensin converting enzyme in vitro and in vivo. In general, the addition of lipophilic substituents to the 4-position of proline of the parent phosphonate 1 resulted in substantial increases in in vitro activity. The largest improvements were observed in the case of cis-benzyl (36-fold) and dithioketal (24-fold) analogues 2r and 2x, respectively. These enhancements of in vitro activity were accompanied by modest increases (2-3.5-fold) in in vivo (iv) activity. Among the various terminal amino acid replacements examined in this study, the indoline-based analogue 2i was by far the most potent compound on iv administration in the normotensive rat.

  DOI：

  10.1021/jm00167a028