N-[2-(S)-(3,5-difluorophenyl)-1-(R)-(4-ethyl-5-oxo-THF-2-yl)ethyl]-N',N'-dipropylisophthalamide | 485389-90-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[2-(S)-(3,5-difluorophenyl)-1-(R)-(4-ethyl-5-oxo-THF-2-yl)ethyl]-N',N'-dipropylisophthalamide
• 英文别名: N-{2-(3,5-Difluorophenyl)-(1S,2S,4R)-[1-(4-ethyl-5-oxotetrahydrofuran-2-yl)]ethyl}-N',N'-dipropylisophthalamide；1-N-[(1S)-2-(3,5-difluorophenyl)-1-[(2S,4R)-4-ethyl-5-oxooxolan-2-yl]ethyl]-3-N,3-N-dipropylbenzene-1,3-dicarboxamide
• CAS: 485389-90-0
• 化学式: C₂₈H₃₄F₂N₂O₄
• 分子量: 500.586
• InChiKey: QDHDICIEBNHJGG-NGXZDTIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-氨基丁酸 、 N-[2-(S)-(3,5-difluorophenyl)-1-(R)-(4-ethyl-5-oxo-THF-2-yl)ethyl]-N',N'-dipropylisophthalamide 在 三甲基铝 作用下， 以 二氯甲烷 为溶剂， 生成 4-[(2R,4S,5S)-6-(3,5-difluorophenyl)-5-{[3-(dipropylcarbamoyl)phenyl]formamido}-2-ethyl-4-hydroxyhexanamido]butanoic acid
  参考文献：
  名称：

  Design and Synthesis of Hydroxyethylene-Based Peptidomimetic Inhibitors of Human β-Secretase

  摘要：

  The hydroxyethylene (HE) transition state isostere was developed as a scaffold to provide potent, small molecule inhibitors of human beta-secretase (BACE). The previous work on the statine series proved critical to the discovery of HE structure-activity relationships. Compound 20 with the N-terminal isophthalamide proved to be the most potent HE inhibitor (IC50 = 30 nM) toward BACK Unlike the statine series, we identified HE inhibitors without carboxylic acids on the C terminus, leading to enhanced cell penetration and making them attractive candidates for further drug development in Alzheimer's disease.

  DOI：

  10.1021/jm0304008
• 作为产物：
  描述：

  [(S)-2-(3,5-Difluoro-phenyl)-1-((2S,4R)-4-ethyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 生成 N-[2-(S)-(3,5-difluorophenyl)-1-(R)-(4-ethyl-5-oxo-THF-2-yl)ethyl]-N',N'-dipropylisophthalamide
  参考文献：
  名称：

  Design and Synthesis of Hydroxyethylene-Based Peptidomimetic Inhibitors of Human β-Secretase

  摘要：

  The hydroxyethylene (HE) transition state isostere was developed as a scaffold to provide potent, small molecule inhibitors of human beta-secretase (BACE). The previous work on the statine series proved critical to the discovery of HE structure-activity relationships. Compound 20 with the N-terminal isophthalamide proved to be the most potent HE inhibitor (IC50 = 30 nM) toward BACK Unlike the statine series, we identified HE inhibitors without carboxylic acids on the C terminus, leading to enhanced cell penetration and making them attractive candidates for further drug development in Alzheimer's disease.

  DOI：

  10.1021/jm0304008

文献信息

• Compounds to treat Alzheimer's disease
  申请人：——

  公开号：US20030013881A1

  公开（公告）日：2003-01-16

  The present invention is directed toward substituted hydroxyethylene compounds of formulas (XII) (XIII), and (XIV) 1 useful in treating Alzheimer's disease and other similar diseases.

  本发明涉及用于治疗阿尔茨海默病和其他类似疾病的式（XII）、（XIII）和（XIV）的替代羟基乙烯化合物。
• Design and Synthesis of Hydroxyethylene-Based Peptidomimetic Inhibitors of Human β-Secretase
  作者：Roy K. Hom、Andrea F. Gailunas、Shumeye Mamo、Larry Y. Fang、Jay S. Tung、Donald E. Walker、David Davis、Eugene D. Thorsett、Nancy E. Jewett、Joseph B. Moon、Varghese John

  DOI：10.1021/jm0304008

  日期：2004.1.1

  The hydroxyethylene (HE) transition state isostere was developed as a scaffold to provide potent, small molecule inhibitors of human beta-secretase (BACE). The previous work on the statine series proved critical to the discovery of HE structure-activity relationships. Compound 20 with the N-terminal isophthalamide proved to be the most potent HE inhibitor (IC50 = 30 nM) toward BACK Unlike the statine series, we identified HE inhibitors without carboxylic acids on the C terminus, leading to enhanced cell penetration and making them attractive candidates for further drug development in Alzheimer's disease.