N¹-(2,3-dihydro-1H-inden-2-yl)-N¹-(prop-1-yl)butane-1,4-diamine | 1194814-34-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N¹-(2,3-dihydro-1H-inden-2-yl)-N¹-(prop-1-yl)butane-1,4-diamine
• 英文别名: N¹-(2,3-dihydro-1H-indan-2-yl)-N¹-propylbutane-1,4-diamine；(N-indan-2-yl-N-propyl)butane-1,4-diamine；N'-(2,3-dihydro-1H-inden-2-yl)-N'-propylbutane-1,4-diamine
• CAS: 1194814-34-0
• 化学式: C₁₆H₂₆N₂
• 分子量: 246.396
• InChiKey: LBCNLIPQWQMKLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N¹-(2,3-dihydro-1H-inden-2-yl)-N¹-(prop-1-yl)butane-1,4-diamine 在 copper(ll) sulfate pentahydrate 、 TATU 、 sodium ascorbate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 4-[3-[1-[8-[4-[3-[4-[[[4-[(indan-2-yl)(propyl)amino]butyl]amino]carbonyl]-2-methoxyphenoxy]propyl]-1H-1,2,3-triazol-1-yl]octyl]-1H-1,2,3-triazol-4-yl]propoxy]-3-methoxy-N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzamide
  参考文献：
  名称：

  Development of a Bivalent Dopamine D₂ Receptor Agonist

  摘要：

  Bivalent D-2 agonists may function as useful molecular probes for the discovery of novel neurological therapeutics. On the basis of our recently developed bivalent dopamine D-2 receptor antagonists of type 1, the bivalent agonist 2 was synthesized when a spacer built from 22 atoms was employed. Compared to the monovalent control compound 6 containing a capped spacer, the bis-aminoindane derivative 2 revealed substantial steepening of the competition curve, indicating a bivalent binding mode. Dimer-specific Hill slopes were not a result of varying functional properties because both the dopaminergic 2 and the monovalent control agent 6 proved to be D-2 agonists substantially inhibiting cAMP accumulation and inducing D-2 receptor internalization. Investigation of the heterobivalent ligands 8 and 9, containing an agonist and a phenylpiperazine-based antagonist pharmacophore, revealed moderate steepening of the displacement curves and antagonist to very weak partial agonist properties.

  DOI：

  10.1021/jm2009919
• 作为产物：
  描述：

  N-(2,3-dihydro-1H-inden-2-yl)-N-(prop-1-yl)amine 在 lithium aluminium tetrahydride 作用下， 以 乙醚 、 乙腈 为溶剂， 生成 N¹-(2,3-dihydro-1H-inden-2-yl)-N¹-(prop-1-yl)butane-1,4-diamine
  参考文献：
  名称：

  作为强效多巴胺 D2 受体激动剂的双位配体的合成

  摘要：

  最佳间隔长度：在这项研究中，我们合成了十二个双位配体作为多巴胺 D 2受体激动剂。有趣的是，化合物11b的效力比先导化合物2高 21 倍，对 D 2 R 的亚型选择性比 D 4 R高 17 倍。分子模型研究表明，11 b与氨基酸 Asp114 形成了两个 H 键，这有助于D 2 R 功能活性显着。

  DOI：

  10.1002/cmdc.202100681

文献信息

• Photochromic Dopamine Receptor Ligands Based on Dithienylethenes and Fulgides
  作者：Daniel Lachmann、Carolin Studte、Barbara Männel、Harald Hübner、Peter Gmeiner、Burkhard König

  DOI：10.1002/chem.201702147

  日期：2017.9.27

  a known twisted intramolecular charge transfer (TICT). Several cyclopentene‐DTEs showed high PSS, but a fast degradation by forming an irreversible byproduct. Focusing on the fulgides, high photostationary states and switching in polar solvents were possible. The compounds 43, 45 and 46 containing the isopropyl group showed only isomerization between the open E‐form and the closed C‐form. At a concentration

  我们描述了将经过充分研究的一类光致变色二噻吩基乙烯（DTE）和fulgides掺入已知的多巴胺受体配体中，例如1,4-二取代的芳族和羟基苯并恶嗪酮哌嗪以及氨基茚满。获得亚型和功能性选择性光致变色配体，并通过NMR和UV / VIS光谱测量进行表征。基于DTE的多巴胺配体的光物理性质显示出对二芳基马来酰亚胺的高抗疲劳性，但是由于已知的扭曲的分子内电荷转移（TICT），在极性溶剂中无法实现闭环。几种环戊烯-DTE表现出较高的PSS，但由于形成不可逆的副产物而迅速降解。着眼于杀虫剂，高光平稳态和极性溶剂的转换是可能的。化合物43，45和46含有异丙基表现出开放E-型和闭合C-形式之间仅异构化。在浓度为1 n m的条件下，环戊烯-DTE 29开环显示的D 2S（一种具有药理学意义的G蛋白偶联受体）的活化程度比其封闭的光致变色同类物29高出11倍以上。有趣的是，基于氟替米酰亚胺的对52-（E）-open
• Discovery of a true bivalent dopamine D2 receptor agonist
  作者：Mingcheng Qian、Adrián Ricarte、Elise Wouters、James A.R. Dalton、Martijn D.P. Risseeuw、Jesús Giraldo、Serge Van Calenbergh

  DOI：10.1016/j.ejmech.2020.113151

  日期：2021.2

  Employing two different alkyne-modified dopamine agonists to construct bivalent compounds via click chemistry resulted in the identification of a bivalent ligand (11c) for dopamine D2 receptor homodimer, which, compared to its parent monomeric alkyne, showed a 16-fold higher binding affinity for the dopamine D2 receptor and a 5-fold higher potency in a cAMP assay in HEK 293T cells stably expressing

  使用两种不同的炔烃修饰的多巴胺激动剂通过点击化学方法构建二价化合物，从而鉴定出多巴胺D 2受体同型二聚体的二价配体（11c），与其母体单体炔烃相比，其结合亲和力高16倍对多巴胺d 2受体和5倍于HEK 293T细胞中稳定表达d一个cAMP测定更高的效力2 R.分子建模揭示，11c中，的确可以桥接d的正构结合位点2经由R个同型二聚体在松弛构TM5-TM6接口，并可以在很大程度上合理化受体测定的结果。
• 一种多巴胺D₂受体双位配体型化合物和应用
  申请人：常州大学

  公开号：CN113979915B

  公开（公告）日：2023-07-25

  本发明属于药物化学领域，具体公开了一种多巴胺D2受体双位配体型化合物和应用。本发明的目标化合物以3个部分构造而成，左侧结构为多巴胺D2受体的正构配体，中间的结构为连接链(linker)，右侧为别构配体。本发明通过抑制forskolin诱导产生的cAMP的累积实验用来测试目标化合物对D2R的功能活性以及阐明新化合物对D2R与D4R两种受体亚型的选择性。结果显示合成的一系列双位配体的化合物对D2R具有较高的功能活性。
• Fluoro-substituted phenylazocarboxamides: Dopaminergic behavior and N-arylating properties for irreversible binding
  作者：Amelie L. Bartuschat、Tamara Schellhorn、Harald Hübner、Peter Gmeiner、Markus R. Heinrich

  DOI：10.1016/j.bmc.2014.12.012

  日期：2015.7

  Phenylazocarboxamides can serve as bioisosteres for cinnamides, which are widely occurring substructures in medicinal chemistry. Starting from our lead compound 2, the introduction of additional fluoro substituents and the exchange of the methoxyphenylpiperazine head group by an aminoindane moiety was investigated resulting in dopamine D-3 receptor antagonists and agonists with K-i values in the sub- and low-nanomolar range. As a potentially irreversible ligand, the 3,4,5-trifluoro-substituted phenylazocarboxamide 7 was investigated for its N-arylating properties by incubation with the protected lysine analog 18 and with the L89K mutant of the dopamine D-3 receptor. Whereas covalent bond formation with the lysine unit in TM2 of D-3 could not be detected, substantial N-arylation of the side chain of the model compound 18 has been observed. (C) 2014 Elsevier Ltd. All rights reserved.
• Highly Potent 5-Aminotetrahydropyrazolopyridines: Enantioselective Dopamine D₃ Receptor Binding, Functional Selectivity, and Analysis of Receptor−Ligand Interactions
  作者：Nuska Tschammer、Jan Elsner、Angela Goetz、Katharina Ehrlich、Stefan Schuster、Miriam Ruberg、Julia Kühhorn、Dawn Thompson、Jennifer Whistler、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm101639t

  日期：2011.4.14

  Heterocyclic dopamine surrogates of types 5 and 7 were synthesized and investigated for their dopaminergic properties. The enantiomerically pure biphenylcarboxamide (S)-5a displayed an outstanding K-i of 27 pM at the agonist-labeled D-3 receptor and significant selectivity over the D-2 subtype. Measurement of [S-35]GTP gamma S incorporation in the presence of a coexpressed PTX-insensitive G(alpha 0-1) subunit indicated highly efficient G-protein coupling. Comparison of ligand efficacy data from cAMP accumulation and [H-3]thymidine incorporation experiments revealed that ligand biased signaling is exerted by the test compound (S)-5a. Starting from the D-3 crystal structure, a combination of homology modeling and site directed mutagenesis gave valuable insights into the binding mode and the intermolecular origins of stereospecific receptor recognition. According to these data, the superior affinity of the eutomer 5a is caused by the favorable binding energy that results from interaction between the ligand's central ammonium unit and the aspartate residue in position 3.32 of the receptor.