2-Methoxy-4-amino-5-chlorobenzoic acid 2-piperazinoethyl ester | 307973-17-7

• 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-Methoxy-4-amino-5-chlorobenzoic acid 2-piperazinoethyl ester
• 英文别名: 2-piperazin-1-ylethyl 4-amino-5-chloro-2-methoxybenzoate
• CAS: 307973-17-7
• 化学式: C₁₄H₂₀ClN₃O₃
• 分子量: 313.784
• InChiKey: STXPSWHCNHJFSS-UHFFFAOYSA-N

物化性质

• 熔点：
  244 °C
• 沸点：
  490.6±45.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  庚二酸 、 2-Methoxy-4-amino-5-chlorobenzoic acid 2-piperazinoethyl ester 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以91%的产率得到1-[2-(3-Amino-4-chloro-2-methoxyphenylcarbonyloxy)ethyl]-4-(7-{4-[2-(4-amino-5-chloro-2-methoxyphenylcarbonyloxy)ethyl]hexahydro-1-pyrazinyl}-7-oxoheptanoyl)hexahydropyrazine
  参考文献：
  名称：

  Design and Synthesis of Specific Probes for Human 5-HT₄ Receptor Dimerization Studies

  摘要：

  Recently, human 5-HT4 receptors have been demonstrated to form constitutive dimers in living cells. To evaluate the role of dimerization on the 5-HT4 receptor function, we investigated the conception and the synthesis of bivalent molecules able to influence the dimerization process. Their conception is based on a model of the 5-HT4 receptor dimer derived from protein/protein docking experiments. These bivalent ligands are constituted by two ML10302 units, a specific 5-HT4 ligand, linked through a spacer of different sizes and natures. These synthesized bivalent ligands were evaluated in binding assays and cyclic AMP production on the 5-HT4(e/g) receptor isoform stably transfected in C6 glial cells. Our data showed that bivalent ligands conserved a similar affinity compared to the basal ML10302 unit. Nevertheless, according to the nature and the size of the spacer, the pharmacological profile of ML10302 is more or less conserved. In view of the interest of bivalent ligands for investigating the GPCR dimerization process, these 5-HT4 specific bivalent ligands constitute valuable pharmacological tools for the study of 5-HT4 receptor dimerization.

  DOI：

  10.1021/jm050234z
• 作为产物：
  描述：

  4-[2-(4-Amino-5-chloro-2-methoxy-benzoyloxy)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester 在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以96%的产率得到2-Methoxy-4-amino-5-chlorobenzoic acid 2-piperazinoethyl ester
  参考文献：
  名称：

  新的芳基哌嗪衍生物作为人类克隆的5-HT（4）受体亚型的拮抗剂。

  摘要：

  芳基哌嗪9的新衍生物是根据ML 10302（在胃肠系统中有效的5-HT（4）受体激动剂）设计的。通过将许多可得的芳基哌嗪或杂芳基哌嗪与2-溴乙基4-氨基-5-氯-2-甲氧基苯甲酸酯缩合来合成化合物。他们在结合测定中评估了最近克隆的人5-HT（4（e））同工型，在C6神经胶质细胞中稳定表达，[[3] H] GR 113808作为放射性配体。亲和力值（K（i））取决于芳环上的取代基。氯原子的活性显着下降（K（i）> 100 nM），而间甲氧基生成的化合物具有纳摩尔摩尔亲和力（K（i）= 3 nM）。最有效的化合物是具有嘧啶，吡嗪，哒嗪或吡啶部分的杂环衍生物（分别为化合物9r，9t，9u，9x）。确定了5-HT（4（a）），5-HT（4（b）），5-HT（4（c））和5-HT（4（ d））在COS细胞中瞬时表达的受体同工型。结果表明这些化合物不是选择性的。他们在稳定表达5-HT（4（e））受体的

  DOI：

  10.1021/jm0009538

文献信息

• Design and Synthesis of Specific Probes for Human 5-HT₄ Receptor Dimerization Studies
  作者：Jean-Louis Soulier、Olivier Russo、Mireille Giner、Lucie Rivail、Magali Berthouze、Sandrine Ongeri、Bernard Maigret、Rodolphe Fischmeister、Frank Lezoualc'h、Sames Sicsic、Isabelle Berque-Bestel

  DOI：10.1021/jm050234z

  日期：2005.10.1

  Recently, human 5-HT4 receptors have been demonstrated to form constitutive dimers in living cells. To evaluate the role of dimerization on the 5-HT4 receptor function, we investigated the conception and the synthesis of bivalent molecules able to influence the dimerization process. Their conception is based on a model of the 5-HT4 receptor dimer derived from protein/protein docking experiments. These bivalent ligands are constituted by two ML10302 units, a specific 5-HT4 ligand, linked through a spacer of different sizes and natures. These synthesized bivalent ligands were evaluated in binding assays and cyclic AMP production on the 5-HT4(e/g) receptor isoform stably transfected in C6 glial cells. Our data showed that bivalent ligands conserved a similar affinity compared to the basal ML10302 unit. Nevertheless, according to the nature and the size of the spacer, the pharmacological profile of ML10302 is more or less conserved. In view of the interest of bivalent ligands for investigating the GPCR dimerization process, these 5-HT4 specific bivalent ligands constitute valuable pharmacological tools for the study of 5-HT4 receptor dimerization.
• New Arylpiperazine Derivatives as Antagonists of the Human Cloned 5-HT₄ Receptor Isoforms
  作者：Sophie Curtet、Jean-Louis Soulier、Ivan Zahradnik、Mireille Giner、Isabelle Berque-Bestel、Jeanne Mialet、Frank Lezoualc'h、Patrick Donzeau-Gouge、Sames Sicsic、Rodolphe Fischmeister、Michel Langlois

  DOI：10.1021/jm0009538

  日期：2000.10.1

  depended upon the substituent on the aromatic ring. A chlorine atom produced a marked drop in activity (K(i) > 100 nM), while a m-methoxy group gave a compound with nanomolar affinity (K(i) = 3 nM). The most potent compounds were the heterocyclic derivatives with pyrimidine, pyrazine, pyridazine, or pyridine moieties (compounds 9r, 9t, 9u, 9x, respectively). K(i) values for 9a and 9r were determined

  芳基哌嗪9的新衍生物是根据ML 10302（在胃肠系统中有效的5-HT（4）受体激动剂）设计的。通过将许多可得的芳基哌嗪或杂芳基哌嗪与2-溴乙基4-氨基-5-氯-2-甲氧基苯甲酸酯缩合来合成化合物。他们在结合测定中评估了最近克隆的人5-HT（4（e））同工型，在C6神经胶质细胞中稳定表达，[[3] H] GR 113808作为放射性配体。亲和力值（K（i））取决于芳环上的取代基。氯原子的活性显着下降（K（i）> 100 nM），而间甲氧基生成的化合物具有纳摩尔摩尔亲和力（K（i）= 3 nM）。最有效的化合物是具有嘧啶，吡嗪，哒嗪或吡啶部分的杂环衍生物（分别为化合物9r，9t，9u，9x）。确定了5-HT（4（a）），5-HT（4（b）），5-HT（4（c））和5-HT（4（ d））在COS细胞中瞬时表达的受体同工型。结果表明这些化合物不是选择性的。他们在稳定表达5-HT（4（e））受体的