3(R)-<(acetylthio)methyl>-2-oxo-1-azacyclodecane-10(S)-carboxylic acid | 150198-21-3

• 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: 3(R)-<(acetylthio)methyl>-2-oxo-1-azacyclodecane-10(S)-carboxylic acid
• 英文别名: (2S,9R)-9-(acetylsulfanylmethyl)-10-oxoazecane-2-carboxylic acid
• CAS: 150198-21-3
• 化学式: C₁₃H₂₁NO₄S
• 分子量: 287.38
• InChiKey: JNSGCXKEBNBERY-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3(R)-<(acetylthio)methyl>-2-oxo-1-azacyclodecane-10(S)-carboxylic acid 在 N-甲基吗啉 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 trans-N-<<3(R)-(mercaptomethyl)-2-oxo-1-azacyclodec-10(S)-yl>carbonyl>-4-hydroxy-L-proline
  参考文献：
  名称：

  Design and synthesis of an orally active macrocyclic neutral endopeptidase 24.11 inhibitor

  摘要：

  A potent macrocyclic inhibitor of neutral endopeptidase (NEP) 24.11 was designed using a computer model of the active site of thermolysin. This 10-membered ring lactam represents a general mimic for any hydrophobic dipeptide in which the two amino acid side chains bind to an enzyme in a contiguous orientation. The parent 10-membered ring lactam was synthesized and exhibited excellent potency as an NEP 24.11 inhibitor (IC50 = 3 nM). In order to improve oral bioavailability, various functionality was attached to the macrocycle. These modifications lead to CGS 25155, an orally active NEP 24.11 inhibitor that slows down the degradation of the cardiac hormone atrial natriuretic factor, producing a lowering of blood pressure in the DOCA-salt rat model of hypertension.

  DOI：

  10.1021/jm00076a009
• 作为产物：
  描述：

  ethyl 2,3-dioxo-1-azacyclodecane-10-carboxylate 在 吡啶 、 lithium hydroxide 、 sodium hydroxide 、 正丁基锂 、 三氟化硼乙醚 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 32.83h， 生成 3(R)-<(acetylthio)methyl>-2-oxo-1-azacyclodecane-10(S)-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of an orally active macrocyclic neutral endopeptidase 24.11 inhibitor

  摘要：

  A potent macrocyclic inhibitor of neutral endopeptidase (NEP) 24.11 was designed using a computer model of the active site of thermolysin. This 10-membered ring lactam represents a general mimic for any hydrophobic dipeptide in which the two amino acid side chains bind to an enzyme in a contiguous orientation. The parent 10-membered ring lactam was synthesized and exhibited excellent potency as an NEP 24.11 inhibitor (IC50 = 3 nM). In order to improve oral bioavailability, various functionality was attached to the macrocycle. These modifications lead to CGS 25155, an orally active NEP 24.11 inhibitor that slows down the degradation of the cardiac hormone atrial natriuretic factor, producing a lowering of blood pressure in the DOCA-salt rat model of hypertension.

  DOI：

  10.1021/jm00076a009