(S)-1-(2,2-Dimethyl-propionyl)-pyrrolidine-2-carboxylic acid {(R)-1-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-hydroxy-propylcarbamoyl]-2-naphthalen-2-yl-ethyl}-amide | 881660-62-4

• 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: (S)-1-(2,2-Dimethyl-propionyl)-pyrrolidine-2-carboxylic acid {(R)-1-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-hydroxy-propylcarbamoyl]-2-naphthalen-2-yl-ethyl}-amide
• CAS: 881660-62-4
• 化学式: C₃₄H₃₈N₄O₆
• 分子量: 598.699
• InChiKey: CSXUMUGFSDMEFV-OTJOWVLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  44.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  136.12
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-1-(2,2-Dimethyl-propionyl)-pyrrolidine-2-carboxylic acid {(R)-1-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-hydroxy-propylcarbamoyl]-2-naphthalen-2-yl-ethyl}-amide 在 sodium cyanoborohydride 、 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 N-[3-(2,2-dimethylpropylamino)-2-hydroxypropyl]-2(R)-[1-(2,2-dimethylpropionyl)-pyrrolidine-2(S)-carbonylamino]-3-naphthalen-2-yl-propionamide hydrochloride
  参考文献：
  名称：

  Novel Series of Highly Potent Non-peptide Growth Hormone Secretagogues with Im- proved Bioavailability

  摘要：

  The discovery and the SAR of acylproline derivatives as highly potent growth hormone secretagogues (GHSs) with good oral bioavailability are described. One representative compound, N-[3-(2,2-dimethylpropylamino)-2hydroxypropyl]-2(R)-[ 1-(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]3-naphthalen-2-ylpropionamide (4e), showed potent GHS activity (ED50=1 nM) and good oral bioavailability (BA=33.2%). Moreover, the optically pure N-[3-(2,2-dimethylpropylamino)-2(S)-hydroxypropyl]-2(R)-[ I -(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]-3-naphthalen-2-ylpropionamide ((2S)-4c) showed a good metabolic stability against in vitro clearance (human liver microsome) with potent GHS activity.

  DOI：

  10.3987/com-05-s(t)73
• 作为产物：
  描述：

  methyl (2R)-2-amino-3-(2-naphthyl)propanoate 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-1-(2,2-Dimethyl-propionyl)-pyrrolidine-2-carboxylic acid {(R)-1-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-hydroxy-propylcarbamoyl]-2-naphthalen-2-yl-ethyl}-amide
  参考文献：
  名称：

  Novel Series of Highly Potent Non-peptide Growth Hormone Secretagogues with Im- proved Bioavailability

  摘要：

  The discovery and the SAR of acylproline derivatives as highly potent growth hormone secretagogues (GHSs) with good oral bioavailability are described. One representative compound, N-[3-(2,2-dimethylpropylamino)-2hydroxypropyl]-2(R)-[ 1-(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]3-naphthalen-2-ylpropionamide (4e), showed potent GHS activity (ED50=1 nM) and good oral bioavailability (BA=33.2%). Moreover, the optically pure N-[3-(2,2-dimethylpropylamino)-2(S)-hydroxypropyl]-2(R)-[ I -(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]-3-naphthalen-2-ylpropionamide ((2S)-4c) showed a good metabolic stability against in vitro clearance (human liver microsome) with potent GHS activity.

  DOI：

  10.3987/com-05-s(t)73