(R)-2-(4-chlorobenzensulfonylamino)-4-methylpentanoic acid amide | 553619-61-7

• 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: (R)-2-(4-chlorobenzensulfonylamino)-4-methylpentanoic acid amide
• 英文别名: N-(4-chlorobenzenesulfonyl)-D-leucinamide；(2R)-2-(4-Chlorobenzenesulfonylamino)-4-methylpentanoic acid amide；(2R)-2-[(4-chlorophenyl)sulfonylamino]-4-methylpentanamide
• CAS: 553619-61-7
• 化学式: C₁₂H₁₇ClN₂O₃S
• 分子量: 304.798
• InChiKey: KHWZZRKECVSOOQ-LLVKDONJSA-N

物化性质

• 熔点：
  228-229 °C
• 沸点：
  481.8±55.0 °C(Predicted)
• 密度：
  1.291±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  胡椒基氯 、 (R)-2-(4-chlorobenzensulfonylamino)-4-methylpentanoic acid amide 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69%的产率得到N-(4-chlorobenzenesulfonyl)-N-piperonyl-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：

  D-leucinamide hydrochloride 、 4-氯苯磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以90%的产率得到(R)-2-(4-chlorobenzensulfonylamino)-4-methylpentanoic acid amide
  参考文献：
  名称：

  2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors

  摘要：

  A series of (N-benzyl-N-phenylsulfonamido)alkyl amides were developed from classic and parallel synthesis strategies. Compounds with good in vitro and in vivo gamma-secretase activity were identified and described. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.057

文献信息

• Alpha-(N-sulfonamido)acetamide derivatives as beta-amyloid inhibitors
  申请人：——

  公开号：US20040127494A1

  公开（公告）日：2004-07-01

  There is provided a series of novel &agr;-(N-sulfonamido)acetamide compounds of the Formula (I) 1 wherein R, R 1 , R 2 and R 3 are defined herein, which are inhibitors of &bgr;-amyloid peptide (&bgr;-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by anti-amyloid activity.

  提供了一系列新型的&agr;-(N-磺酰胺基)乙酰胺化合物，化学式为(I)1，其中R、R1、R2和R3在此定义，它们是&bgr;-淀粉样肽(&bgr;-AP)产生的抑制剂，可用于治疗阿尔茨海默病和其他受抗淀粉样活性影响的疾病。
• ALPHA-(N-SULFONAMIDO)ACETAMIDE DERIVATIVES AS BETA-AMYLOID INHIBITORS
  申请人：Parker F. Michael

  公开号：US20080085894A1

  公开（公告）日：2008-04-10

  There is provided a series of novel α-(N-sulfonamido)acetamide compounds of the Formula (I) wherein R, R 1 , R 2 and R 3 are defined herein, which are inhibitors of β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by anti-amyloid activity.

  提供了一系列新型α-(N-磺酰胺基)乙酰胺化合物的公式(I)，其中R、R1、R2和R3在此定义，它们是β-淀粉样肽（β-AP）产生的抑制剂，并且在治疗阿尔茨海默病和其他受到抗淀粉样蛋白活性影响的疾病中有用。
• α-(N-sulfonamido)acetamide derivatives as β-amyloid inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US07300936B2

  公开（公告）日：2007-11-27

  There is provided a series of novel α-(N-sulfonamido)acetamide compounds of the Formula (I) wherein R, R1, R2 and R3 are defined herein, which are inhibitors of β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by anti-amyloid activity.

  提供了一系列新型α-(N-磺酰胺基)乙酰胺化合物，化学式为(I)，其中R、R1、R2和R3在此定义，它们是β-淀粉样肽(β-AP)产生的抑制剂，并且在治疗阿尔茨海默病和其他受抗淀粉样活性影响的疾病中有用。
• Alpha-(N-Sulfonamido)Acetamide Derivatives as Beta-Amyloid Inhibitors
  申请人：Parker Michael F.

  公开号：US20110105485A1

  公开（公告）日：2011-05-05

  There is provided a series of novel α-(N-sulfonamido)acetamide compounds of the Formula (I) wherein R, R 1 , R 2 and R 3 are defined herein, which are inhibitors of β-amyloid peptide (β-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions affected by anti-amyloid activity.

  提供了一系列新型的α-(N-磺酰胺基)乙酰胺化合物(I式)，其中R、R1、R2和R3如本文所定义，它们是β-淀粉样肽（β-AP）产生的抑制剂，并且在治疗阿尔茨海默病和其他受抗淀粉样蛋白活性影响的疾病中有用。
• 2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors
  作者：Michael F. Parker、Donna M. Barten、Carl P. Bergstrom、Joanne J. Bronson、Jason A. Corsa、Michael F. Dee、Yonghua Gai、Valerie L. Guss、Mendi A. Higgins、Daniel J. Keavy、Alice Loo、Robert A. Mate、Larry R. Marcin、Katharine E. McElhone、Craig T. Polson、Susan B. Roberts、John E. Macor

  DOI：10.1016/j.bmcl.2012.09.057

  日期：2012.11

  A series of (N-benzyl-N-phenylsulfonamido)alkyl amides were developed from classic and parallel synthesis strategies. Compounds with good in vitro and in vivo gamma-secretase activity were identified and described. (C) 2012 Elsevier Ltd. All rights reserved.