tert-butyl-3-(((3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)propyl)(methyl)amino)methyl)-5-methoxy-1H-indole-1-carboxylate | 1507402-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl-3-(((3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)propyl)(methyl)amino)methyl)-5-methoxy-1H-indole-1-carboxylate
• 英文别名: tert-butyl 3-[[3-[5-cyano-1-(4-fluorophenyl)-3H-2-benzofuran-1-yl]propyl-methylamino]methyl]-5-methoxyindole-1-carboxylate
• CAS: 1507402-11-0
• 化学式: C₃₄H₃₆FN₃O₄
• 分子量: 569.676
• InChiKey: ZYUFVTVSVUKZJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.13
• 重原子数：
  42.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  76.72
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl-3-(((3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)propyl)(methyl)amino)methyl)-5-methoxy-1H-indole-1-carboxylate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以61%的产率得到1-(4-fluorophenyl)-1-(3-(((5-methoxy-1H-indol-3-yl)methyl)-(methyl)amino)propyl)-1,3-dihydroisobenzofuran-5-carbonitrile
  参考文献：
  名称：

  Design and Synthesis of 1-(3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites

  摘要：

  The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (+/-)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT Si site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [H-3]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT Si site (K-i = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [H-3]S-1 via S2.

  DOI：

  10.1021/jm4014136
• 作为产物：
  描述：

  西酞普兰 在 1-氯乙基氯甲酸酯 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 tert-butyl-3-(((3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)propyl)(methyl)amino)methyl)-5-methoxy-1H-indole-1-carboxylate
  参考文献：
  名称：

  Design and Synthesis of 1-(3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites

  摘要：

  The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (+/-)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT Si site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [H-3]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT Si site (K-i = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [H-3]S-1 via S2.

  DOI：

  10.1021/jm4014136

文献信息

• Design and Synthesis of 1-(3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites
  作者：Ashwini K. Banala、Peng Zhang、Per Plenge、George Cyriac、Theresa Kopajtic、Jonathan L. Katz、Claus Juul Loland、Amy Hauck Newman

  DOI：10.1021/jm4014136

  日期：2013.12.12

  The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (+/-)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT Si site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [H-3]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT Si site (K-i = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [H-3]S-1 via S2.