2-[[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-(2,3-dihydro-1H-inden-2-yl)amino]acetic acid | 126110-46-1

• 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: 2-[[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-(2,3-dihydro-1H-inden-2-yl)amino]acetic acid
• CAS: 126110-46-1
• 化学式: C₂₇H₃₇N₂O₆P
• 分子量: 516.574
• InChiKey: OITITPKEAFZDQE-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  36
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-2-hydroxy-6<<(phenylmethoxy)carbonyl>amino>hexanoic acid methyl ester 在 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium periodate 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 27.67h， 生成 2-[[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-(2,3-dihydro-1H-inden-2-yl)amino]acetic acid
  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oxy]-1-oxohexyl]-L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and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

• Phosphonate substituted amino or imino acids useful as antihypertensives
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0414190A2

  公开（公告）日：1991-02-27

  This invention is directed to new phosphonate substituted amino or imino acids of the formula isomeric mixtures thereof and pharmaceutically acceptable salts thereof, wherein: X is an imino or amino acid of the formula or which show hypotensive activity.

  本发明涉及新的膦酸盐取代的氨基或亚氨基酸，其式为 其异构体混合物及其药学上可接受的盐，其中X 是式中的亚氨基或氨基酸 或 具有降血压活性。
• US5436245A
  申请人：——

  公开号：US5436245A

  公开（公告）日：1995-07-25