4'-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide | 635289-50-8

• 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: 4'-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide
• 英文别名: (2S,3S)-N-(4-bromophenyl)-1-hydroxy-3-methylpentane-2-sulfonamido；4-bromo-N-[(2S,3S)-1-hydroxy-3-methylpentan-2-yl]benzenesulfonamide
• CAS: 635289-50-8
• 化学式: C₁₂H₁₈BrNO₃S
• 分子量: 336.25
• InChiKey: KRCRTCGHANKNGN-JOYOIKCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 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：
  74.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-异亮氨醇 、 4-溴苯磺酰氯 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 4'-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide
  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

• [EN] SUBSTITUTED PHENYLSULFONAMIDE INHIBITORS OF BETA AMYLOID PRODUCTION<br/>[FR] INHIBITEURS A SUBSTITUTION PHENYLSULFONAMIDE DE LA PRODUCTION DE BETA-AMYLOIDES
  申请人：WYETH CORP

  公开号：WO2003103660A1

  公开（公告）日：2003-12-18

  Compounds of Formula I, wherein R1-R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer’s Disease and Down’s syndrome are described.

  提供了符合以下式I的化合物，其中R1-R8在此处定义，以及其药用盐、水合物、代谢物和/或前药。描述了这些化合物用于抑制β淀粉样蛋白的产生以及预防和治疗阿尔茨海默病和唐氏综合征的用途。
• Substituted phenylsulfonamide inhibitors of beta amyloid production
  申请人：Wyeth

  公开号：US20040006050A1

  公开（公告）日：2004-01-08

  Compounds of Formula I, 1 wherein R 1 -R 8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are described.

  提供公式I,1中R1-R8所定义的化合物，以及其药用盐、水合物、代谢物和/或前药。描述了利用这些化合物抑制β淀粉样蛋白的产生，以及预防和治疗阿尔茨海默病和唐氏综合征的用途。
• Substituted Phenylsulfonamide Inhibitors of Beta Amyloid Production
  申请人：Kreft Anthony Frank

  公开号：US20100120725A1

  公开（公告）日：2010-05-13

  Compounds of Formula I, wherein R 1 -R 8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's disease and Down's syndrome are also described.

  本发明提供了式I的化合物，其中R1-R8在此定义，以及其药学上可接受的盐、水合物、代谢物和/或前药。本发明还描述了使用这些化合物来抑制β淀粉样蛋白的产生以及预防和治疗阿尔茨海默病和唐氏综合症的用途。
• (S)-N-(5-Chlorothiophene-2-sulfonyl)-β,β-diethylalaninol a Notch-1-sparing γ-secretase inhibitor
  作者：Derek C. Cole、Joseph R. Stock、Anthony F. Kreft、Madelene Antane、Suzan H. Aschmies、Kevin P. Atchison、David S. Casebier、Thomas A. Comery、George Diamantidis、John W. Ellingboe、Boyd L. Harrison、Yun Hu、Mei Jin、Dennis M. Kubrak、Peimin Lu、Charles W. Mann、Robert L. Martone、William J. Moore、Aram Oganesian、David R. Riddell、June Sonnenberg-Reines、Shaiu-Ching Sun、Erik Wagner、Zheng Wang、Kevin R. Woller、Zheng Xu、Hua Zhou、J. Steven Jacobsen

  DOI：10.1016/j.bmcl.2008.11.116

  日期：2009.2

  Accumulation of beta-amyloid (A beta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) gamma-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (A beta (40/42) EC50 = 28 nM), which is efficacious in reduction of A beta production in vivo. (C) 2008 Elsevier Ltd. All rights reserved.
• Discovery of a novel series of Notch-sparing γ-secretase inhibitors
  作者：Anthony Kreft、Boyd Harrison、Suzan Aschmies、Kevin Atchison、David Casebier、Derek C. Cole、George Diamantidis、John Ellingboe、Diane Hauze、Yun Hu、Donna Huryn、Mei Jin、Dennis Kubrak、Peimin Lu、Joseph Lundquist、Charles Mann、Robert Martone、William Moore、Aram Oganesian、Alex Porte、Dave R. Riddell、June Sonnenberg-Reines、Joseph R. Stock、Shaiu-Ching Sun、Erik Wagner、Kevin Woller、Zheng Xu、Hua Zhou、J. Steven Jacobsen

  DOI：10.1016/j.bmcl.2008.05.064

  日期：2008.7

  Using a cell-based assay, we have identified a new series of Notch-sparing gamma-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved gamma-secretase inhibitory potency and Notch-sparing selectivity. (C) 2008 Elsevier Ltd. All rights reserved.