2-iodo-N-[(S)-{(S)-1-piperidin-2-yl}(phenyl)methyl]3-(trifluoromethyl)benzamide | 1345961-25-2

• 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: 2-iodo-N-[(S)-{(S)-1-piperidin-2-yl}(phenyl)methyl]3-(trifluoromethyl)benzamide
• 英文别名: 2-iodo-N-[(S)-phenyl-[(2S)-piperidin-2-yl]methyl]-3-(trifluoromethyl)benzamide
• CAS: 1345961-25-2
• 化学式: C₂₀H₂₀F₃IN₂O
• 分子量: 488.291
• InChiKey: BCQCONAZRLELLX-WMZOPIPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 2-iodo-N-[(S)-{(S)-1-piperidin-2-yl}(phenyl)methyl]3-(trifluoromethyl)benzamide 在 三乙酰氧基硼氢化钠 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以95%的产率得到2-iodo-N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl)methyl]3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Synthesis and characterization of [125I]2-iodo N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl)methyl]3-trifluoromethyl-benzamide as novel imaging probe for glycine transporter 1

  摘要：

  In this study, 2-iodo substituted 1-methylpiperidin-2-yl benzamide derivatives were synthesized and evaluated as candidate SPECT imaging agents for glycine transporter 1 (GlyT1). In JAR cells, which predominantly express GlyT1, 2-iodo N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl) methyl]3-trifluoromethyl-benzamide (5) showed excellent inhibitory activity of [H-3] glycine uptake (IC50 = 2.4 nM). Saturation assay in rat cortical membranes revealed that [I-125] 5 had a single high affinity binding site with a K-d of 1.54 nM and a B-max of 3.40 pmol/mg protein. In vitro autoradiography demonstrated that [I-125]5 showed consistent accumulation with GlyT1 expression. The in vitro binding was greatly inhibited by GlyT1 inhibitors but not by other site ligands, which suggested the high specific binding of [I-125]5 with GlyT1. In the biodistribution and ex vivo autoradiography studies using mice, [I-125]5 showed high blood-brain barrier permeability (1.68-2.17% dose/g at 15-60 min) and similar regional brain distribution pattern with in vitro results. In addition, pre-treatment of GlyT1 ligands resulted in significant decrease of [I-125]5 binding in the GlyT1-rich regions. This preliminary study demonstrated that radio-iodinated 5 is a promising SPECT imaging probe for GlyT1. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.010
• 作为产物：
  描述：

  N-[(S)-{(S)-1-allylpiperidin-2-yl}(phenyl)methyl]-2-iodo 3-(trifluoromethyl)benzamide 在 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以88%的产率得到2-iodo-N-[(S)-{(S)-1-piperidin-2-yl}(phenyl)methyl]3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Synthesis and characterization of [125I]2-iodo N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl)methyl]3-trifluoromethyl-benzamide as novel imaging probe for glycine transporter 1

  摘要：

  In this study, 2-iodo substituted 1-methylpiperidin-2-yl benzamide derivatives were synthesized and evaluated as candidate SPECT imaging agents for glycine transporter 1 (GlyT1). In JAR cells, which predominantly express GlyT1, 2-iodo N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl) methyl]3-trifluoromethyl-benzamide (5) showed excellent inhibitory activity of [H-3] glycine uptake (IC50 = 2.4 nM). Saturation assay in rat cortical membranes revealed that [I-125] 5 had a single high affinity binding site with a K-d of 1.54 nM and a B-max of 3.40 pmol/mg protein. In vitro autoradiography demonstrated that [I-125]5 showed consistent accumulation with GlyT1 expression. The in vitro binding was greatly inhibited by GlyT1 inhibitors but not by other site ligands, which suggested the high specific binding of [I-125]5 with GlyT1. In the biodistribution and ex vivo autoradiography studies using mice, [I-125]5 showed high blood-brain barrier permeability (1.68-2.17% dose/g at 15-60 min) and similar regional brain distribution pattern with in vitro results. In addition, pre-treatment of GlyT1 ligands resulted in significant decrease of [I-125]5 binding in the GlyT1-rich regions. This preliminary study demonstrated that radio-iodinated 5 is a promising SPECT imaging probe for GlyT1. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.010

文献信息

• Synthesis and characterization of [125I]2-iodo N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl)methyl]3-trifluoromethyl-benzamide as novel imaging probe for glycine transporter 1
  作者：Takeshi Fuchigami、Mamoru Haratake、Yasuhiro Magata、Terushi Haradahira、Morio Nakayama

  DOI：10.1016/j.bmc.2011.09.010

  日期：2011.11

  In this study, 2-iodo substituted 1-methylpiperidin-2-yl benzamide derivatives were synthesized and evaluated as candidate SPECT imaging agents for glycine transporter 1 (GlyT1). In JAR cells, which predominantly express GlyT1, 2-iodo N-[(S)-(S)-1-methylpiperidin-2-yl}(phenyl) methyl]3-trifluoromethyl-benzamide (5) showed excellent inhibitory activity of [H-3] glycine uptake (IC50 = 2.4 nM). Saturation assay in rat cortical membranes revealed that [I-125] 5 had a single high affinity binding site with a K-d of 1.54 nM and a B-max of 3.40 pmol/mg protein. In vitro autoradiography demonstrated that [I-125]5 showed consistent accumulation with GlyT1 expression. The in vitro binding was greatly inhibited by GlyT1 inhibitors but not by other site ligands, which suggested the high specific binding of [I-125]5 with GlyT1. In the biodistribution and ex vivo autoradiography studies using mice, [I-125]5 showed high blood-brain barrier permeability (1.68-2.17% dose/g at 15-60 min) and similar regional brain distribution pattern with in vitro results. In addition, pre-treatment of GlyT1 ligands resulted in significant decrease of [I-125]5 binding in the GlyT1-rich regions. This preliminary study demonstrated that radio-iodinated 5 is a promising SPECT imaging probe for GlyT1. (C) 2011 Elsevier Ltd. All rights reserved.