benzyl (2S)-4-cyano-4-[(3-fluorophenyl)amino]-2-methylpiperidine-1-carboxylate | 1193782-29-4

• 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: benzyl (2S)-4-cyano-4-[(3-fluorophenyl)amino]-2-methylpiperidine-1-carboxylate
• 英文别名: benzyl (2S)-4-cyano-4-(3-fluoroanilino)-2-methylpiperidine-1-carboxylate
• CAS: 1193782-29-4
• 化学式: C₂₁H₂₂FN₃O₂
• 分子量: 367.423
• InChiKey: KTEGGOXSIVMIRM-BJQOMGFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-4-cyano-4-[(3-fluorophenyl)amino]-2-methylpiperidine-1-carboxylate 在 palladium(II) hydroxide copper(l) iodide 、 氨 、 氢气 、 镍 、 potassium carbonate 、 溶剂黄146 、 N,N'-二甲基乙二胺 、 3-(imidazole-1-sulfonyl)-1-methyl-3H-imidazol-1-ium triflate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 20.0~105.0 ℃ 、344.75 kPa 条件下， 反应 17.0h， 生成 (5R,7S)-1-(3-fluorophenyl)-8-(3-isopropoxybenzyl)-7-methyl-3-(5-phenyl-4,5-dihydroisoxazol-3-yl)-2-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide
  参考文献：
  名称：

  [EN] NOVEL CLASS OF SPIRO PIPERIDINES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  [FR] NOUVELLE CLASSE DE SPIRO PIPÉRIDINES POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES

  摘要：

  本发明揭示了化合物及其在规范中定义的结构为化学式（I）的药用可接受盐。同时还揭示了相应的药用组合物、治疗方法、合成方法和中间体。

  公开号：

  WO2009136350A1
• 作为产物：
  描述：

  3,4-二氢-2-甲基-4-氧代吡啶-1(2H)-甲酸苄酯 在 溶剂黄146 、 二乙胺 、 锌 作用下， 以 甲醇 为溶剂， 反应 10.0h， 生成 benzyl (2S)-4-cyano-4-[(3-fluorophenyl)amino]-2-methylpiperidine-1-carboxylate
  参考文献：
  名称：

  Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency

  摘要：

  The IC50 of a beta-secretase (BACE-1) lead compound was improved similar to 200-fold from 11 mu M to 55 nM through the addition of a single methyl group. Computational chemistry, small molecule NMR, and protein crystallography capabilities were used to compare the solution conformation of the ligand under varying pH conditions to its conformation when bound in the active site. Chemical modification then explored available binding pockets adjacent to the ligand. A strategically placed methyl group not only maintained the required pKa of the piperidine nitrogen and filled a small hydrophobic pocket, but more importantly, stabilized the conformation best suited for optimized binding to the receptor. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.082

文献信息

• Novel Class of Spiro Piperidines for the Treatment of Neurodegenerative Diseases
  申请人：Brodney Michael A.

  公开号：US20110046160A1

  公开（公告）日：2011-02-24

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  本发明公开了化合物及其药用可接受盐，其中该化合物具有规范中定义的公式（I）的结构。同时还公开了相应的药物组合物、治疗方法、合成方法和中间体。
• NOVEL CLASS OF SPIRO PIPERIDINES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Pfizer Inc.

  公开号：EP2300484A1

  公开（公告）日：2011-03-30
• Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency
  作者：Melissa Egbertson、Georgia B. McGaughey、Steven M. Pitzenberger、Shaun R. Stauffer、Craig A. Coburn、Shawn J. Stachel、Wenjin Yang、James C. Barrow、Lou Anne Neilson、Melody McWherter、Debra Perlow、Bruce Fahr、Sanjeev Munshi、Timothy J. Allison、Katharine Holloway、Harold G. Selnick、ZhiQiang Yang、John Swestock、Adam J. Simon、Sethu Sankaranarayanan、Dennis Colussi、Katherine Tugusheva、Ming-Tain Lai、Beth Pietrak、Shari Haugabook、Lixia Jin、I.-W. Chen、Marie Holahan、Maria Stranieri-Michener、Jacquelynn J. Cook、Joseph Vacca、Samuel L. Graham

  DOI：10.1016/j.bmcl.2015.06.082

  日期：2015.11

  The IC50 of a beta-secretase (BACE-1) lead compound was improved similar to 200-fold from 11 mu M to 55 nM through the addition of a single methyl group. Computational chemistry, small molecule NMR, and protein crystallography capabilities were used to compare the solution conformation of the ligand under varying pH conditions to its conformation when bound in the active site. Chemical modification then explored available binding pockets adjacent to the ligand. A strategically placed methyl group not only maintained the required pKa of the piperidine nitrogen and filled a small hydrophobic pocket, but more importantly, stabilized the conformation best suited for optimized binding to the receptor. (C) 2015 Elsevier Ltd. All rights reserved.
• [EN] NOVEL CLASS OF SPIRO PIPERIDINES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] NOUVELLE CLASSE DE SPIRO PIPÉRIDINES POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：PFIZER

  公开号：WO2009136350A1

  公开（公告）日：2009-11-12

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  本发明揭示了化合物及其在规范中定义的结构为化学式（I）的药用可接受盐。同时还揭示了相应的药用组合物、治疗方法、合成方法和中间体。