(S)-1-[(S)-2-[Hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-6-(2,2,2-trifluoro-acetylamino)-hexanoyl]-4,4-bis-methylsulfanyl-pyrrolidine-2-carboxylic acid methyl ester | 126110-85-8

• 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: (S)-1-[(S)-2-[Hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-6-(2,2,2-trifluoro-acetylamino)-hexanoyl]-4,4-bis-methylsulfanyl-pyrrolidine-2-carboxylic acid methyl ester
• 英文别名: [(2S)-1-[(2S)-2-methoxycarbonyl-4,4-bis(methylsulfanyl)pyrrolidin-1-yl]-1-oxo-6-[(2,2,2-trifluoroacetyl)amino]hexan-2-yl]oxy-(4-phenylbutyl)phosphinic acid
• CAS: 126110-85-8
• 化学式: C₂₆H₃₈F₃N₂O₇PS₂
• 分子量: 642.698
• InChiKey: IIZSHVPQICGTEY-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  173
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S)-1-[(S)-2-[Hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-6-(2,2,2-trifluoro-acetylamino)-hexanoyl]-4,4-bis-methylsulfanyl-pyrrolidine-2-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以44%的产率得到Lithium; (S)-1-{(S)-6-amino-2-[hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-hexanoyl}-4,4-bis-methylsulfanyl-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oxy]-1-oxohexyl]-L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and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-[Hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-6-(2,2,2-trifluoro-acetylamino)-hexanoic acid benzyl ester 在 palladium on activated charcoal 氢气 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 25.0 ℃ 、206.84 kPa 条件下， 反应 7.5h， 生成 (S)-1-[(S)-2-[Hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-6-(2,2,2-trifluoro-acetylamino)-hexanoyl]-4,4-bis-methylsulfanyl-pyrrolidine-2-carboxylic acid methyl ester
  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

文献信息

• KARANEWSKY, DONALD S.;BADIA, MICHAEL C.;CUSHMAN, DAVID W.;DEFORREST, JACK+, J. MED. CHEM., 33,(1990) N, C. 1459-1469
  作者：KARANEWSKY, DONALD S.、BADIA, MICHAEL C.、CUSHMAN, DAVID W.、DEFORREST, JACK+

  DOI：——

  日期：——