N-((2-(pyridin-2-yl)ethyloxy)carbonyl)-L-leucine succinimidyl ester | 854402-93-0

• 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: N-((2-(pyridin-2-yl)ethyloxy)carbonyl)-L-leucine succinimidyl ester
• CAS: 854402-93-0
• 化学式: C₁₈H₂₃N₃O₆
• 分子量: 377.397
• InChiKey: UFLIRKUTMWKSHC-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.37
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  114.9
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-((2-(pyridin-2-yl)ethyloxy)carbonyl)-L-leucine succinimidyl ester 在 三氧化硫吡啶 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 ((1S)-1-((((1S)-1-benzyl-3-(cyclopropylamino)-2,3-dioxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 2-(pyridin-2-yl)ethyl ester
  参考文献：
  名称：

  Exploration of orally available calpain inhibitors. Part 3: Dipeptidyl α-ketoamide derivatives containing pyridine moiety

  摘要：

  Calpain-mediated proteolysis has been implicated as a major process in neuronal cell death including retinal neurological degeneration. The previously reported calpain inhibitor SJA6017 (1) showed oral efficacy in a retinal pharmacological model, but its oral bioavailability was low due to the metabolic lability and low water-solubility. The purpose of present study was to identify good orally bioavailable calpain inhibitors. A series of water-soluble dipeptidyl alpha-ketoamides containing a pyridine moiety at P3 were designed, synthesized, and evaluated for their oral bioavailability and retinal penetration. Introduction of a pyridineethanol moiety provided the potent alpha-ketoamide inhibitor 8 with good oral bioavailability. Compound 8 showed about 12-fold higher retinal AUC than 1. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.04.013
• 作为产物：
  描述：

  N-((2-(pyridin-2-yl)ethyloxy)carbonyl)-L-leucine ethyl ester 在 sodium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 N-((2-(pyridin-2-yl)ethyloxy)carbonyl)-L-leucine succinimidyl ester
  参考文献：
  名称：

  Exploration of orally available calpain inhibitors. Part 3: Dipeptidyl α-ketoamide derivatives containing pyridine moiety

  摘要：

  Calpain-mediated proteolysis has been implicated as a major process in neuronal cell death including retinal neurological degeneration. The previously reported calpain inhibitor SJA6017 (1) showed oral efficacy in a retinal pharmacological model, but its oral bioavailability was low due to the metabolic lability and low water-solubility. The purpose of present study was to identify good orally bioavailable calpain inhibitors. A series of water-soluble dipeptidyl alpha-ketoamides containing a pyridine moiety at P3 were designed, synthesized, and evaluated for their oral bioavailability and retinal penetration. Introduction of a pyridineethanol moiety provided the potent alpha-ketoamide inhibitor 8 with good oral bioavailability. Compound 8 showed about 12-fold higher retinal AUC than 1. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.04.013