1,1-二甲基乙基 [3-[3-(3,4-二甲氧基苯基)-1-氧代-丙基]苯氧基]-乙酸酯 | 178445-86-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 中文名称: 1,1-二甲基乙基 [3-[3-(3,4-二甲氧基苯基)-1-氧代-丙基]苯氧基]-乙酸酯
• 中文别名: 1,1-二甲基乙基[3-[3-(3,4-二甲氧基苯基)-1-氧代-丙基]苯氧基]-乙酸酯
• 英文名称: tert-butyl 2-(3-(3-(3,4-dimethoxyphenyl)propanoyl)phenoxy)acetate
• 英文别名: tert-butyl 2-[3-[3-(3,4-dimethoxyphenyl)propanoyl]phenoxy]acetate
• CAS: 178445-86-8
• 化学式: C₂₃H₂₈O₆
• 分子量: 400.472
• InChiKey: ALZNWMXUAQSCSA-UHFFFAOYSA-N

物化性质

• 沸点：
  521.9±50.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  1,1-二甲基乙基 [3-[3-(3,4-二甲氧基苯基)-1-氧代-丙基]苯氧基]-乙酸酯 在 4-二甲氨基吡啶 、 Noyori catalyst (ABCR AB₁₃₁₆₀₀) 、 氢气 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 20.0 ℃ 、1.5 MPa 条件下， 反应 156.0h， 生成 (S)-1-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid (R)-1-(3-tert-butoxycarbonylmethoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-propyl ester
  参考文献：
  名称：

  Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52

  摘要：

  The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.

  DOI：

  10.1021/jm201746x
• 作为产物：
  描述：

  3-(3-(3,4-dimethoxyphenyl)-1-hydroxypropyl)phenol 在 potassium carbonate 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1,1-二甲基乙基 [3-[3-(3,4-二甲氧基苯基)-1-氧代-丙基]苯氧基]-乙酸酯
  参考文献：
  名称：

  RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF

  摘要：

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。

  公开号：

  US20210094933A1

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。
• Targeted Covalent Inhibition of <i>Plasmodium</i> FK506 Binding Protein 35
  作者：Thomas C. Atack、Donald D. Raymond、Christa A. Blomquist、Charisse Flerida Pasaje、Patrick R. McCarren、Jamie Moroco、Henock B. Befekadu、Foxy P. Robinson、Debjani Pal、Lisl Y. Esherick、Alessandra Ianari、Jacquin C. Niles、William R. Sellers

  DOI：10.1021/acsmedchemlett.0c00272

  日期：2020.11.12

  protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects. In contrast to human FKBPs, FKBP35

  FK506结合蛋白35，FKBP35，已被认为是必需的疟疾酶。雷帕霉素和FK506在培养的寄生虫中表现出抗疟原虫活性。然而，由于FKBP的结合口袋的高度保守的性质和这些药物的免疫抑制特性，需要选择性地抑制FKBP35并且缺乏不良副作用的化合物。与人FKBP相比，FKBP35在雷帕霉素结合口袋附近包含一个半胱氨酸C106，为开发靶向疟原虫FKBP35的共价抑制剂提供了机会。在这里，我们合成了FKBP35的抑制剂，表明它们在模型细胞环境中直接结合FKBP35，选择性地共价修饰C106，并在血阶段培养的寄生虫中表现出抗疟原虫活性。
• Synthetic multimerizing agents
  申请人：Ariad Pharmaceuticals, Inc.

  公开号：US06150527A1

  公开（公告）日：2000-11-21

  New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formula M-L-Q where M is a synthetic ligand for an FKBP protein

  新的化合物被披露用于多聚免疫蛋白和含有免疫蛋白或免疫蛋白相关结构域的蛋白质。这些化合物的公式为M-L-Q，其中M是FKBP蛋白的合成配体。
• [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：EP2607352A1

  公开（公告）日：2013-06-26

  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。