N-(4-chlorobenzenesulfonyl)-N-(4-fluorobenzyl)-D-leucinamide | 553614-32-7

• 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-(4-chlorobenzenesulfonyl)-N-(4-fluorobenzyl)-D-leucinamide
• 英文别名: (2R)-2-[(4-chlorophenyl)sulfonyl-[(4-fluorophenyl)methyl]amino]-4-methylpentanamide
• CAS: 553614-32-7
• 化学式: C₁₉H₂₂ClFN₂O₃S
• 分子量: 412.913
• InChiKey: SJAQKCZLABEOFS-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  88.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  D-leucinamide hydrochloride 在 potassium carbonate 、 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 N-(4-chlorobenzenesulfonyl)-N-(4-fluorobenzyl)-D-leucinamide
  参考文献：
  名称：

  Discovery of small molecular (d)-leucinamides as potent, Notch-sparing γ-secretase modulators

  摘要：

  Structural optimization of the prior lead 3 led to the small molecular (D)-leucinamides with potent modulating activity and Notch-sparing selectivity on the proteolytic processing of amyloid-beta precursor proteins. The N-(R)-epoxypropyl analog 10c exhibited potent gamma-secretase modulation compared to DAPT and showed substantial substrate selection for APP cleavage over Notch cleavage, while N-(2-fluoro) benzyl analog 10e showed the most potent gamma-secretase inhibition with dull selectivity. The exceptional suppression of ERIK-mediated activation suggested that these potent gamma-secretase modulators may adapt an alternative pathway to prominently induce the differential inhibition of C99 cleavage by gamma-secretase. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.006

文献信息

• Discovery of small molecular (d)-leucinamides as potent, Notch-sparing γ-secretase modulators
  作者：Yung-Feng Liao、Yu-Cheng Tang、Ming-Yun Chang、Bo-Jeng Wang、Ming-Kuan Hu

  DOI：10.1016/j.ejmech.2014.04.006

  日期：2014.5

  Structural optimization of the prior lead 3 led to the small molecular (D)-leucinamides with potent modulating activity and Notch-sparing selectivity on the proteolytic processing of amyloid-beta precursor proteins. The N-(R)-epoxypropyl analog 10c exhibited potent gamma-secretase modulation compared to DAPT and showed substantial substrate selection for APP cleavage over Notch cleavage, while N-(2-fluoro) benzyl analog 10e showed the most potent gamma-secretase inhibition with dull selectivity. The exceptional suppression of ERIK-mediated activation suggested that these potent gamma-secretase modulators may adapt an alternative pathway to prominently induce the differential inhibition of C99 cleavage by gamma-secretase. (C) 2014 Elsevier Masson SAS. All rights reserved.