N,N-dimethyl-2-(4'-methyl-2'-nitrophenylthio)-5-bromo-benzamide | 1005412-85-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N,N-dimethyl-2-(4'-methyl-2'-nitrophenylthio)-5-bromo-benzamide
• 英文别名: 5-bromo-N,N-dimethyl-2-(4-methyl-2-nitrophenyl)sulfanylbenzamide
• CAS: 1005412-85-0
• 化学式: C₁₆H₁₅BrN₂O₃S
• 分子量: 395.277
• InChiKey: OFQPPAHSQIQGFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-2-(4'-methyl-2'-nitrophenylthio)-5-bromo-benzamide 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 反应 18.0h， 以57%的产率得到N,N-dimethyl-2-(4'-bromomethyl-2'-nitrophenylthio)-5-bromo-benzamide
  参考文献：
  名称：

  Synthesis and In Vivo Evaluation of Halogenated N,N-Dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine Derivatives as PET Serotonin Transporter Ligands

  摘要：

  N,N-Dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benylamine (38), substituted on ring A, was reported to display high binding affinity and selectivity to the human brain serotonin transporter (SERT). In an attempt to explore the potential of compounds substituted on ring B of the phenylthiophenyl core structure, three derivatives of 38 were synthesized: N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-fluorobenzylamine (35), N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-bromobenzylamine (36), and N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-iodobenzylamine (37). The in vitro binding studies in cells transfected with human SERT, norepinephrine transporter (NET), and dopamine transporter (DAT) showed that 35, 36, and 37 exhibited high SERT affinity with K(i)s (SERT) = 1.26, 0.29, and 0.31 nM (vs [H-3]citalopram), respectively. [C-11-(35), [C-11-(36), and [C-11-(37) were prepared by methylation of their monomethyl precursors 16, 17, and 18, with [C-11]iodomethane in 28, 11, and 14% radiochemical yields, respectively. The microPET images of [C-11-(35), [C-11-(36), and [C-11-(37) showed high uptake in the monkey brain regions rich in SERT with peak midbrain to cerebellum ratios of 3.41, 3.24, and 3.00 at 85 min post-injection, respectively. In vivo bindings of [C-11-(35), [C-11-(36), and [C-11-(37) were shown to be specific to the SERT as displacement with citalopram (a potent SERT ligand) reduced radioactivity in SERT-rich regions to the cerebellum level. These results suggest that [C-11-(35), [C-11-(36), and [C-11-(37) could be potential agents for mapping human SERT by PET and radiolabeling 37 with iodine-123, which could afford the first SPECT SERT imaging agent exhibiting fast kinetics.

  DOI：

  10.1021/jm0707929
• 作为产物：
  描述：

  5-Bromo-2-(4-methyl-2-nitrophenyl)sulfanylbenzoyl chloride 、 二甲胺 以 四氢呋喃 为溶剂， 以0.56 g的产率得到N,N-dimethyl-2-(4'-methyl-2'-nitrophenylthio)-5-bromo-benzamide
  参考文献：
  名称：

  Synthesis and In Vivo Evaluation of Halogenated N,N-Dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine Derivatives as PET Serotonin Transporter Ligands

  摘要：

  N,N-Dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benylamine (38), substituted on ring A, was reported to display high binding affinity and selectivity to the human brain serotonin transporter (SERT). In an attempt to explore the potential of compounds substituted on ring B of the phenylthiophenyl core structure, three derivatives of 38 were synthesized: N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-fluorobenzylamine (35), N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-bromobenzylamine (36), and N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-iodobenzylamine (37). The in vitro binding studies in cells transfected with human SERT, norepinephrine transporter (NET), and dopamine transporter (DAT) showed that 35, 36, and 37 exhibited high SERT affinity with K(i)s (SERT) = 1.26, 0.29, and 0.31 nM (vs [H-3]citalopram), respectively. [C-11-(35), [C-11-(36), and [C-11-(37) were prepared by methylation of their monomethyl precursors 16, 17, and 18, with [C-11]iodomethane in 28, 11, and 14% radiochemical yields, respectively. The microPET images of [C-11-(35), [C-11-(36), and [C-11-(37) showed high uptake in the monkey brain regions rich in SERT with peak midbrain to cerebellum ratios of 3.41, 3.24, and 3.00 at 85 min post-injection, respectively. In vivo bindings of [C-11-(35), [C-11-(36), and [C-11-(37) were shown to be specific to the SERT as displacement with citalopram (a potent SERT ligand) reduced radioactivity in SERT-rich regions to the cerebellum level. These results suggest that [C-11-(35), [C-11-(36), and [C-11-(37) could be potential agents for mapping human SERT by PET and radiolabeling 37 with iodine-123, which could afford the first SPECT SERT imaging agent exhibiting fast kinetics.

  DOI：

  10.1021/jm0707929

文献信息

• Synthesis and In Vivo Evaluation of Halogenated <i>N</i>,<i>N</i>-Dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine Derivatives as PET Serotonin Transporter Ligands
  作者：Nachwa Jarkas、Ronald J. Voll、Larry Williams、John R. Votaw、Mike Owens、Mark M. Goodman

  DOI：10.1021/jm0707929

  日期：2008.1.1

  N,N-Dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benylamine (38), substituted on ring A, was reported to display high binding affinity and selectivity to the human brain serotonin transporter (SERT). In an attempt to explore the potential of compounds substituted on ring B of the phenylthiophenyl core structure, three derivatives of 38 were synthesized: N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-fluorobenzylamine (35), N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-bromobenzylamine (36), and N,N-dimethyl-2-(2'-amino-4'-hydroxymethyl-phenylthio)-5-iodobenzylamine (37). The in vitro binding studies in cells transfected with human SERT, norepinephrine transporter (NET), and dopamine transporter (DAT) showed that 35, 36, and 37 exhibited high SERT affinity with K(i)s (SERT) = 1.26, 0.29, and 0.31 nM (vs [H-3]citalopram), respectively. [C-11-(35), [C-11-(36), and [C-11-(37) were prepared by methylation of their monomethyl precursors 16, 17, and 18, with [C-11]iodomethane in 28, 11, and 14% radiochemical yields, respectively. The microPET images of [C-11-(35), [C-11-(36), and [C-11-(37) showed high uptake in the monkey brain regions rich in SERT with peak midbrain to cerebellum ratios of 3.41, 3.24, and 3.00 at 85 min post-injection, respectively. In vivo bindings of [C-11-(35), [C-11-(36), and [C-11-(37) were shown to be specific to the SERT as displacement with citalopram (a potent SERT ligand) reduced radioactivity in SERT-rich regions to the cerebellum level. These results suggest that [C-11-(35), [C-11-(36), and [C-11-(37) could be potential agents for mapping human SERT by PET and radiolabeling 37 with iodine-123, which could afford the first SPECT SERT imaging agent exhibiting fast kinetics.