L-valine, 4,4,4,4',4',4'-hexafluoro-N-[(1R)-1-phenylethyl]-, ethyl ester, hydrochloride | 946615-66-3

• 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: L-valine, 4,4,4,4',4',4'-hexafluoro-N-[(1R)-1-phenylethyl]-, ethyl ester, hydrochloride
• 英文别名: ethyl 4,4,4,4',4',4'-hexafluoro-N-[(1R)-1-phenylethyl]-L-valinate hydrochloride；ethyl (2S)-4,4,4-trifluoro-2-[[(1R)-1-phenylethyl]amino]-3-(trifluoromethyl)butanoate;hydrochloride
• CAS: 946615-66-3
• 化学式: C₁₅H₁₇F₆NO₂*ClH
• 分子量: 393.757
• InChiKey: VHTKZIMNECRNFZ-XQKZEKTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.43
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.3
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  L-valine, 4,4,4,4',4',4'-hexafluoro-N-[(1R)-1-phenylethyl]-, ethyl ester, hydrochloride 在 sodium hydroxide 、 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 反应 5.5h， 以99%的产率得到(S)-4,4,4-trifluoro-2-((R)-1-phenyl-ethylamino)-3-trifluoromethyl-butan-1-ol
  参考文献：
  名称：

  Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

  摘要：

  SAR on HTS hits I and 2 led to the potent, Notch-l-sparing GSI 9, which lowered brain A beta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5). which was selected for development for the treatment of Alzheimer's disease.

  DOI：

  10.1021/jm801252w

文献信息

• Methods for preparing sulfonamide substituted alcohols and intermediates thereof
  申请人：Chan Anita Wai-Yin

  公开号：US20070197830A1

  公开（公告）日：2007-08-23

  Processes for preparing amino alcohols or salts thereof and sulfonamide substituted alcohol compounds are provided. Desirably, the sulfonamide substituted alcohol compounds are heterocyclic sulfonamide trifluoroalkyl-substituted alcohol compounds or phenyl sulfonamide trifluoroalkyl-substituted alcohol compounds.

  提供了制备氨基醇或其盐以及磺酰胺取代的醇化合物的工艺。理想情况下，磺酰胺取代的醇化合物是杂环磺酰胺三氟烷基取代的醇化合物或苯基磺酰胺三氟烷基取代的醇化合物。
• US7687666B2
  申请人：——

  公开号：US7687666B2

  公开（公告）日：2010-03-30
• Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease
  作者：Scott C. Mayer、Anthony F. Kreft、Boyd Harrison、Magid Abou-Gharbia、Madelene Antane、Suzan Aschmies、Kevin Atchison、Michael Chlenov、Derek C. Cole、Thomas Comery、George Diamantidis、John Ellingboe、Kristi Fan、Rocco Galante、Cathleen Gonzales、Douglas M. Ho、Molly E. Hoke、Yun Hu、Donna Huryn、Uday Jain、Mei Jin、Kenneth Kremer、Dennis Kubrak、Melissa Lin、Peimin Lu、Ron Magolda、Robert Martone、William Moore、Aram Oganesian、Menelas N. Pangalos、Alex Porte、Peter Reinhart、Lynn Resnick、David R. Riddell、June Sonnenberg-Reines、Joseph R. Stock、Shaiu-Ching Sun、Erik Wagner、Ting Wang、Kevin Woller、Zheng Xu、Margaret M. Zaleska、Joseph Zeldis、Minsheng Zhang、Hua Zhou、J. Steven Jacobsen

  DOI：10.1021/jm801252w

  日期：2008.12.11

  SAR on HTS hits I and 2 led to the potent, Notch-l-sparing GSI 9, which lowered brain A beta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5). which was selected for development for the treatment of Alzheimer's disease.