(2R,3S)-N¹-[(S)-1-(3'-Fluoro-biphenyl-3-ylmethyl)-2-oxo-azepan-3-yl]-2-isobutyl-3-propyl-succinamide

• 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: (2R,3S)-N¹-[(S)-1-(3'-Fluoro-biphenyl-3-ylmethyl)-2-oxo-azepan-3-yl]-2-isobutyl-3-propyl-succinamide
• 英文别名: (2S,3R)-N'-[(3S)-1-[[3-(3-fluorophenyl)phenyl]methyl]-2-oxoazepan-3-yl]-3-(2-methylpropyl)-2-propylbutanediamide
• 化学式: C₃₀H₄₀FN₃O₃
• 分子量: 509.664
• InChiKey: DXAMIGRAGGVLFS-VJGNERBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-3-Amino-1-(3-iodo-benzyl)-azepan-2-one 、 (2R,3S)-2-Isobutyl-3-propyl-succinic acid 1-(9H-fluoren-9-ylmethyl) ester 、 3-氟苯基硼酸 生成 (2R,3S)-N¹-[(S)-1-(3'-Fluoro-biphenyl-3-ylmethyl)-2-oxo-azepan-3-yl]-2-isobutyl-3-propyl-succinamide
  参考文献：
  名称：

  Synthesis and evaluation of succinoyl-caprolactam γ-secretase inhibitors

  摘要：

  The synthesis, evaluation, and structure-activity relationships of a series of succinoyl lactam inhibitors of the Alzheimer's disease gamma-secretase are described. Beginning with a screening hit with broad proteinase activity, optimization provided compounds with both high selectivity for inhibition of gamma-secretase and high potency in cellular assays of A beta reduction. The SAR and early in vivo properties of this series of inhibitors will be presented. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.055

文献信息

• Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
  申请人：——

  公开号：US20020159947A1

  公开（公告）日：2002-10-31

  This invention relates to a method of using radiolabelled and/or radiopharmaceutical small molecule inhibitors of beta-amyloid peptide production for the diagnosis of neurological and other disorders involving APP processing and beta-amyloid production. Furthermore, radiolabelled small molecule inhibitors identified by the methods of the present invention would be useful in the diagnosis of neurological disorders, such as Alzheimer's disease, which involve elevated levels of A&bgr; peptides.

  这项发明涉及一种使用放射性标记和/或放射性药物的小分子抑制剂来诊断涉及APP处理和β-淀粉样肽产生的神经和其他疾病的方法。此外，根据本发明方法鉴定的放射性标记小分子抑制剂将有助于诊断涉及Aβ肽水平升高的神经疾病，如阿尔兹海默病。
• Succinoylamino lactams as inhibitors of A-beta protein production
  申请人：Olson E. Richard

  公开号：US20050245501A1

  公开（公告）日：2005-11-03

  This invention relates to novel lactams having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有药物和生物作用特性的新型内酰胺、它们的药物组合物和使用方法。这些新化合物抑制淀粉样前体蛋白的处理，更具体地抑制Aβ肽的产生，从而防止神经淀粉样蛋白沉积物的形成。更具体地，本发明涉及与β-淀粉样蛋白产生相关的神经系统疾病的治疗，例如阿尔茨海默病和唐氏综合症。
• Succinoylamino lactams as inhibitors of a-beta protein production
  申请人：Olson E. Richard

  公开号：US20060264417A1

  公开（公告）日：2006-11-23

  This invention relates to novel lactams having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有药物和生物影响性质的新型内酰胺，其制药组合物和使用方法。这些新化合物抑制淀粉样前体蛋白的处理，更具体地抑制Aβ-肽的产生，从而防止神经沉积物的淀粉样蛋白的形成。更具体地，本发明涉及与β-淀粉样蛋白产生相关的神经系统疾病的治疗，例如阿尔茨海默病和唐氏综合症。
• SUCCINOYLAMINO LACTAMS AS INHIBITORS OF A-BETA PROTEIN PRODUCTION
  申请人：Olson Richard E.

  公开号：US20080293692A1

  公开（公告）日：2008-11-27

  This invention relates to novel lactams having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有药物和生物影响性质的新型内酰胺、其制药组合物和使用方法。这些新化合物抑制淀粉样前体蛋白的加工，更具体地抑制Aβ肽的产生，从而防止神经沉积物的淀粉样蛋白形成。更具体地，本发明涉及与β-淀粉样蛋白产生相关的神经系统疾病的治疗，如阿尔茨海默病和唐氏综合症。
• Use of radioligands to screen inhibitors of amyloid-beta peptide production
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1589342A2

  公开（公告）日：2005-10-26

  This invention relates to a novel method of screening for inhibitors of beta-amyloid production, and thereby identifying such inhibitors as therapeutics for neurological and other disorders involving APP processing and beta-amyloid production. This invention also relates to identifying macromolecules involved in APP processing and beta-amyloid production. Furthermore, inhibitors identified by the screening method of the present invention are useful in the treatment of neurological disorders, such as Alzheimer's disease, which involve elevated levels of Aβ peptides.

  本发明涉及一种筛选β-淀粉样蛋白生成抑制剂的新方法，从而确定这种抑制剂作为治疗涉及APP加工和β-淀粉样蛋白生成的神经系统疾病和其他疾病的药物。本发明还涉及鉴定参与 APP 处理和 beta- 淀粉样蛋白生成的大分子。此外，通过本发明的筛选方法鉴定的抑制剂可用于治疗神经系统疾病，如阿尔茨海默氏症，这种疾病涉及 Aβ 肽水平的升高。