(S)-4-azido-N-((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)-3-iodobenzamide

• 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)-4-azido-N-((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)-3-iodobenzamide
• 英文别名: 4-azido-N-[[(1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3H-2-benzofuran-5-yl]methyl]-3-iodobenzamide
• 化学式: C₂₇H₂₇FIN₅O₂
• 分子量: 599.447
• InChiKey: URMNWEFDTSNZBD-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-4-azido-N-((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)-3-iodobenzamide 、 六正丁基二锡 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以52%的产率得到(S)-4-azido-N-((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)-3-(tri-nbutylstannyl)benzamide
  参考文献：
  名称：

  Novel Azido-Iodo Photoaffinity Ligands for the Human Serotonin Transporter Based on the Selective Serotonin Reuptake Inhibitor (S)-Citalopram

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00682
• 作为产物：
  描述：

  (S)-3-(5-(aminomethyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine 、 4-叠氮基-3-碘苯甲酸 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以67%的产率得到(S)-4-azido-N-((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)-3-iodobenzamide
  参考文献：
  名称：

  Novel Azido-Iodo Photoaffinity Ligands for the Human Serotonin Transporter Based on the Selective Serotonin Reuptake Inhibitor (S)-Citalopram

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00682