t-butyl 2-(3-formylphenoxy)propylcarbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: t-butyl 2-(3-formylphenoxy)propylcarbamate
• 英文别名: tert-butyl N-[2-(3-formylphenoxy)propyl]carbamate
• 化学式: C₁₅H₂₁NO₄
• 分子量: 279.336
• InChiKey: KYVDIEUKZASLMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  t-butyl 2-(3-formylphenoxy)propylcarbamate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 2.08h， 生成 8-[3-(2-amino-1-methylethoxy)benzyl]-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one
  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
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 、 三苯基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 11.0h， 生成 t-butyl 2-(3-formylphenoxy)propylcarbamate
  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

• 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 Sharp & Dohme Corp.

  公开号：EP1804794B1

  公开（公告）日：2013-07-31
• 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.