N-benzyl-4-((2-bromo-5-fluorophenyl)amino)piperidine-4-carbonitrile | 885115-65-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-benzyl-4-((2-bromo-5-fluorophenyl)amino)piperidine-4-carbonitrile
• 英文别名: 1-benzyl-4-[(2-bromo-5-fluorophenyl)amino]piperidine-4-carbonitrile；1-Benzyl-4-(2-bromo-5-fluoroanilino)piperidine-4-carbonitrile
• CAS: 885115-65-1
• 化学式: C₁₉H₁₉BrFN₃
• 分子量: 388.282
• InChiKey: FVILTLCRJOSQLW-UHFFFAOYSA-N

物化性质

• 沸点：
  505.9±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  39.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-benzyl-4-((2-bromo-5-fluorophenyl)amino)piperidine-4-carbonitrile 在 盐酸 、 偶氮二异丁腈 、 水 、 三正丁基氢锡 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of spiroindolines as novel inducers of oligodendrocyte progenitor cell differentiation—Use of a conformation-based hypothesis to facilitate compound design

  摘要：

  Inducing oligodendrocyte progenitor cell (OPC) differentiation is a novel therapeutic strategy for the treatment of demyelinating diseases such as multiple sclerosis (MS). In the preceding article, we detailed the discovery of compound 1, a potent inducer of OPC differentiation possessing a characteristic spiroindoline structure. Also, we found that N-methylation and des-carbonyl compound 1 (4) led to a loss in potency. Herein, we describe our investigations of a conformation-based hypothesis for OPC differentiation activity based on the preferred conformation of the spiro core, and further structure-activity relationship (SAR) exploration led to the identification of 6-CF3 derivative 8, which was more potent compared to compound 1.

  DOI：

  10.1016/j.bmcl.2020.127299
• 作为产物：
  描述：

  N-苄基哌啶酮 、 三甲基氰硅烷 、 2-溴-5-氟苯胺 在 溶剂黄146 作用下， 反应 5.0h， 以51%的产率得到N-benzyl-4-((2-bromo-5-fluorophenyl)amino)piperidine-4-carbonitrile
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of spiroindolines as novel inducers of oligodendrocyte progenitor cell differentiation—Use of a conformation-based hypothesis to facilitate compound design

  摘要：

  Inducing oligodendrocyte progenitor cell (OPC) differentiation is a novel therapeutic strategy for the treatment of demyelinating diseases such as multiple sclerosis (MS). In the preceding article, we detailed the discovery of compound 1, a potent inducer of OPC differentiation possessing a characteristic spiroindoline structure. Also, we found that N-methylation and des-carbonyl compound 1 (4) led to a loss in potency. Herein, we describe our investigations of a conformation-based hypothesis for OPC differentiation activity based on the preferred conformation of the spiro core, and further structure-activity relationship (SAR) exploration led to the identification of 6-CF3 derivative 8, which was more potent compared to compound 1.

  DOI：

  10.1016/j.bmcl.2020.127299

文献信息

• Spiropiperidine compounds useful as beta-secretase inhibitors for the treatment of alzheimer' s disease
  申请人：Barrow C. James

  公开号：US20070197571A1

  公开（公告）日：2007-08-23

  The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及公式（I）的螺环哌啶化合物，它们是β-分泌酶酶的抑制剂，并且在治疗β-分泌酶酶参与的疾病，如阿尔茨海默病中有用。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在治疗β-分泌酶酶参与的疾病中的使用。
• WO2006/44497
  申请人：——

  公开号：——

  公开（公告）日：——
• SPIROPIPERIDINE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHERMER S DISEASE
  申请人：Merck & Co., Inc.

  公开号：EP1804794A2

  公开（公告）日：2007-07-11
• US8114887B2
  申请人：——

  公开号：US8114887B2

  公开（公告）日：2012-02-14
• [EN] SPIROPIPERIDINE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHERMER'S DISEASE<br/>[FR] COMPOSES DE SPIROPIPERIDINE UTILISES COMME INHIBITEURS DE BETA-SECRETASE EN VUE DU TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2006044497A2

  公开（公告）日：2006-04-27

  [EN] The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.
  [FR] Composés de spiropipéridine de formule (I), représentant des inhibiteurs de l'enzyme bêta-sécrétase et utilisés dans le traitement de maladies dans lesquelles l'enzyme bêta-sécrétase est appliquée, notamment la maladie d'Alzheimer. Compositions pharmaceutiques comprenant ces composés, l'utilisation et des compositions de des composés dans le traitement de maladies impliquant l'enzyme bêta-sécrétase.