cis-4-cyclohexyl-L-proline phenylmethyl ester monohydrochloride | 126110-99-4

• 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: cis-4-cyclohexyl-L-proline phenylmethyl ester monohydrochloride
• CAS: 126110-99-4
• 化学式: C₁₈H₂₅NO₂*ClH
• 分子量: 323.863
• InChiKey: HMJNITCOAYGNQQ-QJHJCNPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  cis-4-cyclohexyl-L-proline phenylmethyl ester monohydrochloride 在 4-二甲氨基吡啶 、 sodium periodate 、 1-羟基苯并三唑 、 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 、 水 为溶剂， 反应 20.0h， 生成 (2S,4R)-1-{(S)-6-Benzyloxycarbonylamino-2-[hydroxy-(4-phenyl-butyl)-phosphinoyloxy]-hexanoyl}-4-cyclohexyl-pyrrolidine-2-carboxylic acid benzyl 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oxy]-1-oxohexyl]-L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and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