N-(5-chlorothiophene-2-sulfonyl)-D-leucinamide | 1609199-87-2

• 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-(5-chlorothiophene-2-sulfonyl)-D-leucinamide
• 英文别名: (2R)-2-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methylpentanamide
• CAS: 1609199-87-2
• 化学式: C₁₀H₁₅ClN₂O₃S₂
• 分子量: 310.826
• InChiKey: HKUPERWQQFBPNZ-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  左旋环氧氯丙烷 、 N-(5-chlorothiophene-2-sulfonyl)-D-leucinamide 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以18%的产率得到N-(5-chlorothiophene-2-sulfonyl)-N-((R)-2,3-epoxypropyl)-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
• 作为产物：
  描述：

  5-氯噻唑-2-磺酰氯 、 D-leucinamide hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到N-(5-chlorothiophene-2-sulfonyl)-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