(S)-3-(5-(aminomethyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine | 1585941-33-8

• 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: (S)-3-(5-(aminomethyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine
• 英文别名: 3-(5-(aminomethyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine；5-(aminomethyl)-S-citalopram；3-[(1S)-5-(aminomethyl)-1-(4-fluorophenyl)-3H-2-benzofuran-1-yl]-N,N-dimethylpropan-1-amine
• CAS: 1585941-33-8
• 化学式: C₂₀H₂₅FN₂O
• 分子量: 328.43
• InChiKey: ADGFGICBGFREFM-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(5-(aminomethyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine 、 23-azido-3,6,9,12,15,18,21-heptaoxatricosyl(2,5-dioxopyrrolidin-1-yl) glutarate 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以68%的产率得到23-azido-3,6,9,12,15,18,21-heptaoxatricosyl 5-(((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)amino)-5-oxopentanoate
  参考文献：
  名称：

  纳米药理学力传感揭示转运蛋白结合位点的变构耦合

  摘要：

  关于神经递质/钠同向转运体中配体结合位点的数量和功能的争议源于晶体结构和分子药理学中相互矛盾的数据。在这里，我们设计了新的原子力显微镜工具，可以在单分子水平上直接测量血清素转运蛋白 (SERT) 与西酞普兰的S和R对映体之间的相互作用力。这种方法基于力谱，它允许在生理条件下提取动态信息，因此无法通过 X 射线晶体学获得。在含 Na +的缓冲液中揭示了西酞普兰与 SERT 的两个不同群体的特征结合强度。相反，在 Li +含有缓冲液的 SERT 仅显示低力相互作用。相反，前庭突变体 SERT-G402H 仅显示高力群体。这些观察结果为在生理环境中访问时 SERT 中存在两个结合位点提供了物理证据。竞争实验表明，这两个位点变构耦合并施加相互调制。

  DOI：

  10.1002/anie.201508755
• 作为产物：
  描述：

  依他普仑 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 (S)-3-(5-(aminomethyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine
  参考文献：
  名称：

  Novel and High Affinity Fluorescent Ligands for the Serotonin Transporter Based on (S)-Citalopram

  摘要：

  Novel rhodamine-labeled ligands, based on (S)citalopram, were synthesized and evaluated for uptake inhibition at the human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) and for binding at SERT, in transiently transfected COS7 cells. Compound 14 demonstrated high affinity binding and selectivity for SERT (K-i; = 3 nM). Visualization of SERT, using confocal laser scanning microscopy, validated compound 14 as a novel tool for studying SERT expression and distribution in living cells.

  DOI：

  10.1021/ml5000806

文献信息

• Clickable photoaffinity ligands for the human serotonin transporter based on the selective serotonin reuptake inhibitor (S)-citalopram
  作者：Nageswari Yarravarapu、Laura Geffert、Christopher K. Surratt、Michael Cascio、David J. Lapinsky

  DOI：10.1016/j.bmcl.2018.09.029

  日期：2018.11

  (SSRI) (S)-citalopram that were rationally designed and synthesized to contain a photoreactive benzophenone or an aryl azide for protein target capture via photoaffinity labeling and a terminal alkyne or an aliphatic azide for click chemistry-based proteomics. Specifically, clickable benzophenone-based (S)-citalopram photoprobe 6 (hSERT Ki = 0.16 nM) displayed 11-fold higher binding affinity at hSERT

  迄今为止，靶向人类血清素转运蛋白（hSERT）的光亲和配体的开发已基于放射性同位素（即3 H或125 I），hSERT是一种涉及疾病状态（如抑郁和焦虑）的关键蛋白。而是强调了选择性5-羟色胺再摄取抑制剂（SSRI）（S）-西酞普兰的三种衍生物，这些衍生物经过合理设计和合成，包含光反应性二苯甲酮或芳基叠氮化物，用于通过光亲和标记和末端炔烃或脂族叠氮化物捕获蛋白质靶标。用于基于化学点击的蛋白质组学。具体而言，可点击的基于二苯甲酮的（S）-西酞普兰光电探针6（hSERT K i =（0.16 nM）与（S）-西酞普兰（hSERT K i  = 1.77 nM）相比，在hSERT处显示出11倍的高结合亲和力，随后显示使用纯化的hSERT成功地进行了串联光亲和标记-双正交偶联。给定可点击的光探针可以用于各种应用，这取决于在光亲和标记后通过点击化学将哪个报道分子连接到了报道分子上，预计光探针6将在结构
• Novel Azido-Iodo Photoaffinity Ligands for the Human Serotonin Transporter Based on the Selective Serotonin Reuptake Inhibitor (<i>S</i>)-Citalopram
  作者：Vivek Kumar、Nageswari Yarravarapu、David J. Lapinsky、Danielle Perley、Bruce Felts、Michael J. Tomlinson、Roxanne A. Vaughan、L. Keith Henry、John R. Lever、Amy Hauck Newman

  DOI：10.1021/acs.jmedchem.5b00682

  日期：2015.7.23

  Three photoaffinity ligands (PALs) for the human serotonin transporter (hSERT) were synthesized based on the selective serotonin reuptake inhibitor (SSRI), (S)-citalopram (1). The classic 4-azido-3-iodo-phenyl group was appended to either the C-1 Or C-5 position of the parent molecule, with variable-length linkers, to generate ligands 15, 22, and 26: These ligands retained high to moderate affinity binding (K-i = 24-227 nM) for hSERT, as assessed by [H-3]5-HT transport inhibition. When tested against Ser438Thr hSERT, all three PALs showed dramatic rightward shifts in inhibitory potency, with K-i values ranging from 3.8 to 9.9 mu M, consistent with the role of Ser438 as a key residue for high-affinity binding of many SSRIs, including (S)-citalopram. Photoactivation studies demonstrated irreversible adduction to hSERT by all ligands, but the reduced (S)-citalopram inhibition of labeling by [I-125]15 compared to that by [I-125]22 and [I-125]26 suggests differences in binding mode(s). These radioligands will be useful for characterizing the drug protein binding interactions for (S)-citalopram at hSERT.
• Novel and High Affinity Fluorescent Ligands for the Serotonin Transporter Based on (<i>S</i>)-Citalopram
  作者：Vivek Kumar、Troels Rahbek-Clemmensen、Christian B. Billesbølle、Trine Nygaard Jorgensen、Ulrik Gether、Amy Hauck Newman

  DOI：10.1021/ml5000806

  日期：2014.6.12

  Novel rhodamine-labeled ligands, based on (S)citalopram, were synthesized and evaluated for uptake inhibition at the human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) and for binding at SERT, in transiently transfected COS7 cells. Compound 14 demonstrated high affinity binding and selectivity for SERT (K-i; = 3 nM). Visualization of SERT, using confocal laser scanning microscopy, validated compound 14 as a novel tool for studying SERT expression and distribution in living cells.
• Nanopharmacological Force Sensing to Reveal Allosteric Coupling in Transporter Binding Sites
  作者：Rong Zhu、Doris Sinwel、Peter S. Hasenhuetl、Kusumika Saha、Vivek Kumar、Peng Zhang、Christian Rankl、Marion Holy、Sonja Sucic、Oliver Kudlacek、Andreas Karner、Walter Sandtner、Thomas Stockner、Hermann J. Gruber、Michael Freissmuth、Amy Hauck Newman、Harald H. Sitte、Peter Hinterdorfer

  DOI：10.1002/anie.201508755

  日期：2016.1.26

  distinct populations of characteristic binding strengths of citalopram to SERT were revealed in Na+‐containing buffer. In contrast, in Li+‐containing buffer, SERT showed only low force interactions. Conversely, the vestibular mutant SERT‐G402H merely displayed the high force population. These observations provide physical evidence for the existence of two binding sites in SERT when accessed in a physiological

  关于神经递质/钠同向转运体中配体结合位点的数量和功能的争议源于晶体结构和分子药理学中相互矛盾的数据。在这里，我们设计了新的原子力显微镜工具，可以在单分子水平上直接测量血清素转运蛋白 (SERT) 与西酞普兰的S和R对映体之间的相互作用力。这种方法基于力谱，它允许在生理条件下提取动态信息，因此无法通过 X 射线晶体学获得。在含 Na +的缓冲液中揭示了西酞普兰与 SERT 的两个不同群体的特征结合强度。相反，在 Li +含有缓冲液的 SERT 仅显示低力相互作用。相反，前庭突变体 SERT-G402H 仅显示高力群体。这些观察结果为在生理环境中访问时 SERT 中存在两个结合位点提供了物理证据。竞争实验表明，这两个位点变构耦合并施加相互调制。