(S)-2-(3,4-dimethoxyphenoxy)ethyl piperidine-2-carboxylate | 1373830-22-8

• 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: (S)-2-(3,4-dimethoxyphenoxy)ethyl piperidine-2-carboxylate
• 英文别名: 2-(3,4-dimethoxyphenoxy)ethyl (2S)-piperidine-2-carboxylate
• CAS: 1373830-22-8
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: KLZFBSGWAVFSLL-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-二氯苯磺酰氯 、 (S)-2-(3,4-dimethoxyphenoxy)ethyl piperidine-2-carboxylate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以20%的产率得到(S)-2-(3,4-dimethoxyphenoxy)ethyl 1-(3,5-dichlorophenylsulfonyl)piperidine-2-carboxylate
  参考文献：
  名称：

  胡椒碱磺酰胺作为FK506结合蛋白51和52的粘合剂的探索

  摘要：

  FK506结合蛋白（FKBP）51和52是可调节类固醇激素受体信号转导的伴侣蛋白。编码FKBP51的基因中的单核苷酸多态性已与多种精神疾病有关。雷帕霉素和FK506是两个大环天然产物，它们与大多数FKBP家族成员紧密结合，包括FKBP51和FKBP52。考虑到保留保守的氢键，用磺酰胺对雷帕霉素和FK506的α-酮酰胺部分进行生物等位取代。重点研究了基于固体支持物的合成方案，该方案导致对FKBP51和FKBP52具有亚微摩尔亲和力的配体。一种磺酰胺类似物的分子结合模式通过X射线晶体学证实。

  DOI：

  10.1021/jm201747c
• 作为产物：
  描述：

  3,4-二甲氧基苯酚 在 potassium carbonate 、 三氟乙酸 、 potassium iodide 作用下， 以 氘代丙酮 、 二氯甲烷 、 丙酮 为溶剂， 反应 26.17h， 生成 (S)-2-(3,4-dimethoxyphenoxy)ethyl piperidine-2-carboxylate
  参考文献：
  名称：

  Pipecolate-diketoamides for treatment of psychiatric disorders

  摘要：

  本发明涉及具有吡啶甲酸二酮酰胺骨架的化合物，这些化合物的药用盐以及含有至少一种这些化合物的药物组合物，与药用载体、赋形剂和/或稀释剂一起。所述的吡啶甲酸二酮酰胺化合物可用于预防和/或治疗精神障碍和神经退行性疾病、障碍和症状。

  公开号：

  EP2607352A1

文献信息

• [EN] SELECTIVE FKBP51 LIGANDS FOR TREATMENT OF PSYCHIATRIC DISORDERS<br/>[FR] LIGANDS SÉLECTIFS DE LA FKBP51 DESTINÉS AU TRAITEMENT DE TROUBLES PSYCHIATRIQUES
  申请人：MAX PLANCK GES ZUR FÖRDERUNG DER WISSENSCHAFTEN E V

  公开号：WO2015039758A1

  公开（公告）日：2015-03-26

  The present invention relates to compounds of the general formula (I) having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有选择性FKBP51配体支架的一般式(I)化合物，这些化合物的药学上可接受的盐以及含有至少一种这些化合物的药学上可接受的载体、赋形剂和/或稀释剂的药物组合物。所述选择性FKBP51配体化合物可用于预防和/或治疗精神障碍和神经退行性疾病、障碍和症状。
• [EN] PIPECOLATE-DIKETOAMIDES FOR TREATMENT OF PSYCHIATRIC DISORDERS<br/>[FR] PIPÉCOLATE-DICÉTOAMIDES POUR LE TRAITEMENT DE TROUBLES PSYCHIATRIQUES
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2013091900A1

  公开（公告）日：2013-06-27

  The present invention relates to compounds having a pipecolate diketoamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate diketoamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有吡啶羧酸二酮酰胺骨架的化合物，这些化合物的药用盐以及含有至少一种这些化合物的药物组合物，与药用载体、赋形剂和/或稀释剂一起。所述吡啶羧酸二酮酰胺化合物可用于预防和/或治疗精神障碍和神经退行性疾病、障碍和症状。
• PIPECOLATE-DIKETOAMIDES FOR TREATMENT OF PSYCHIATRIC DISORDERS
  申请人：MAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WISSENSCHAFTEN E.V.

  公开号：US20150018340A1

  公开（公告）日：2015-01-15

  The present invention relates to compounds having a pipecolate diketoamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate diketoamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有pipecolate diketoamide支架的化合物，这些化合物的药学上可接受的盐以及含有至少一种这些化合物的药学上可接受的载体、赋形剂和/或稀释剂的制药组合物。所述的pipecolate diketoamide化合物可以用于精神障碍和神经退行性疾病、疾病和病况的预防和/或治疗。
• Selective FKBP51 ligands for treatment of psychiatric disorders
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：US10246413B2

  公开（公告）日：2019-04-02

  The present invention relates to compounds having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有选择性 FKBP51 配体支架的化合物、这些化合物的药学上可接受的盐以及含有至少一种这些化合物和药学上可接受的载体、赋形剂和/或稀释剂的药物组合物。所述选择性 FKBP51 配体化合物可用于预防和/或治疗精神疾病和神经退行性疾病、紊乱和病症。
• Increasing the Efficiency of Ligands for FK506-Binding Protein 51 by Conformational Control
  作者：Yansong Wang、Alexander Kirschner、Anne-Katrin Fabian、Ranganath Gopalakrishnan、Christoph Kress、Bastiaan Hoogeland、Uwe Koch、Christian Kozany、Andreas Bracher、Felix Hausch

  DOI：10.1021/jm400087k

  日期：2013.5.23

  The design of efficient ligands remains a key challenge in drug discovery. In the quest for lead-like ligands for the FK506-binding protein 51 (FKBP51), we designed two new classes of bicyclic sulfonamides to probe the contribution of conformational energy in these ligands. The [4.3.1] scaffold had consistently higher affinity compared to the [3.3.1] or monocyclic scaffolds, which could be attributed to better preorganization of two key recognition motifs. Surprisingly, the binding of the rigid [4.3.1] scaffold was enthalpy-driven and entropically disfavored compared to the flexible analogues. Cocrystal structures at atomic resolution revealed that the sulfonamide nitrogen in the bicyclic scaffolds can accept an unusual hydrogen bond from Tyr(113) that mimics the putative FKBP transition state. This resulted in the first lead-like, functionally active ligand for FKBP51. Our work exemplifies how atom-efficient ligands can be achieved by careful conformational control even in very open and thus difficult binding sites such as FKBP51.