N-{4-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-but-2-enyl}-4-iodo-benzamide | 675599-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-{4-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-but-2-enyl}-4-iodo-benzamide
• 英文别名: N-[(E)-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]-4-iodobenzamide
• CAS: 675599-26-5
• 化学式: C₂₁H₂₂Cl₂IN₃O
• 分子量: 530.236
• InChiKey: QMKMSUCBVBINOY-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-{4-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-but-2-enyl}-4-iodo-benzamide 生成 N-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-trans-but-2-enyl}-4-iodobenzamide oxalate
  参考文献：
  名称：

  Structurally rigid dopamine d3 receptor selective ligands and process for making them

  摘要：

  描述了一类结构刚性的多巴胺D3受体选择性配体家族。这个结构刚性的多巴胺D3受体选择性配体家族的公式如下：其中A是顺式或反式-CH═CH—，—C═C—或环己烷。B是顺式或反式-CH═CH—或缺失。R1代表一个可选择取代的苯基团，其中所述取代基选自以下组：氢、卤素、氨基、硝基、羟基、烷氧基、烷基、酰基和吡啶基，所述取代可以出现在邻位、间位或对位中的任何一个，或者R1代表一个杂环芳香环。首选的杂环芳香环是吲哚、喹喔啉、吡啶基、嘧啶基或咪唑基。R2和R3可以独立地是氢或卤素，或者R2单独可以是C1、C2或C3烷氧基，m为1或2，n为0、1或2。

  公开号：

  US20060106030A1
• 作为产物：
  描述：

  1-(2,3-二氯苯基)哌嗪 在 碳酸氢钠 、 肼 作用下， 以 乙醇 、 氯仿 、 乙腈 为溶剂， 反应 7.5h， 生成 N-{4-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-but-2-enyl}-4-iodo-benzamide
  参考文献：
  名称：

  Novel Heterocyclic Trans Olefin Analogues of N-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as Selective Probes with High Affinity for the Dopamine D3 Receptor

  摘要：

  Dopamine D3 receptor subtypes have been hypothesized to play a pivotal role in modulating the reinforcing and drug-seeking effects induced by cocaine. However, definitive pharmacological investigations have been hampered by the lack of highly D3 receptor selective compounds that can be used in vivo. To address this problem, the potent and D3-receptor-selective antagonist NGB 2904 (1, 9H-fluorene-2-carboxylic acid {4-[(2,3-dichlorophenyl)-piperazin-1-yl]-butyl} amide, K-i (hD3) = 2.0 nM, K-i (hD2(L)) = 112 nM, D2/D3 selectivity ratio of 56) was chosen as a lead structure for chemical modification in an attempt to reduce its high lipophilicity (c log D = 6.94) while optimizing D3 receptor binding affinity and D2/D3 selectivity. A series of >30 novel analogues were synthesized, and their binding affinities were evaluated in competition binding assays in HEK 293 cells transfected with either D2(L), D3, or D4 human dopamine receptors using the high affinity, selective D2-like receptor antagonist I-125-IABN. Structural diversity in the aryl amide end of the molecule Was found to have a major influence on (sub)nanomolar D3 receptor affinity and D2/D3 selectivity, which was optimized using a more rigid trans-butenyl linker between the aryl amide and the piperazine. Several analogues demonstrated superior D3 receptor binding affinities and selectivities as compared to the parent ligand. Compound 29 (N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine- 2-yl-benzamide) displayed the most promising pharmacological profile (K-i (hD3) = 0.7 nM, K-i (hD2(L)) = 93.3 nM, D2/D3 selectivity ratio of 133). In addition, this ligand inhibited quinpirole stimulation of mitogenesis at human dopamine D3 receptors transfected into Chinese hamster ovary (CHO) cells, with an EC50 value of 3.0 nM. Compound 29 was a nearly 5 times more potent antagonist at the D3 receptor than 1 (EC50 = 14.4 nM). Moreover, a decrease in c log D value of similar to2 orders of magnitude was determined for this novel D3-receptor-preferring ligand, compared to 1. In summary, chemical modification of 1 has resulted in compounds with high affinity and selectivity for D3 receptors. The most promising candidate, compound 29, is currently being evaluated in animal models of cocaine abuse and will provide an important tool with which to elucidate the role of D3 receptors in drug reinforcement in vivo.

  DOI：

  10.1021/jm049465g

文献信息

• STRUCTURALLY RIGID DOPAMINE D3 RECEPTOR SELECTIVE LIGANDS AND PROCESS FOR MAKING THEM
  申请人：Newman Amy

  公开号：US20100068138A1

  公开（公告）日：2010-03-18

  A family of structurally rigid dopamine D3 receptor selective ligands is described. The family of structurally rigid dopamine D3 receptor selective ligands has the formula wherein A is cis or trans —CH═CH—, —C═C—, or cyclohexyl. B is cis or trans —CH═CH— or absent. R1 represents an optionally substituted phenyl group, wherein said substituents are selected from the group consisting of: hydrogen, halogen, amino, nitro, hydroxyl, alkoxy, alkyl, acyl and pyridyl, and said substitution may occur at any of the ortho, meta, or para positions, or R1 represents a heteroaromatic ring. A preferred heteroaromatic ring is indole, quinoxoline, pyridyl, pyrimidyl, or imidazole. R2 and R3 may be independently hydrogen or a halogen, or R2 alone may be C1, C2, or C3 alkoxy, and m is 1 or 2, and n is 0, 1, or 2.

  描述了一类结构刚性的多巴胺D3受体选择性配体。该结构刚性的多巴胺D3受体选择性配体的化学式如下：其中A为顺式或反式-CH═CH—、—C═C—或环己基；B为顺式或反式-CH═CH—或不存在；R1代表一个可选取代的苯基，其中所述取代基选自羟基、卤素、氨基、硝基、烷氧基、烷基、酰基和吡啶基，所述取代可以出现在任何邻、间或对位，或者R1代表一个杂环芳烃环，其中优选的杂环芳烃环为吲哚、喹啉、吡啶基、嘧啶基或咪唑基。R2和R3可以独立地是氢或卤素，或者R2单独可以是C1、C2或C3的烷氧基，m为1或2，n为0、1或2。
• US7605259B2
  申请人：——

  公开号：US7605259B2

  公开（公告）日：2009-10-20
• US8119642B2
  申请人：——

  公开号：US8119642B2

  公开（公告）日：2012-02-21
• Novel Heterocyclic Trans Olefin Analogues of <i>N</i>-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as Selective Probes with High Affinity for the Dopamine D3 Receptor
  作者：Peter Grundt、Erin E. Carlson、Jianjing Cao、Christina J. Bennett、Elizabeth McElveen、Michelle Taylor、Robert R. Luedtke、Amy Hauck Newman

  DOI：10.1021/jm049465g

  日期：2005.2.1

  Dopamine D3 receptor subtypes have been hypothesized to play a pivotal role in modulating the reinforcing and drug-seeking effects induced by cocaine. However, definitive pharmacological investigations have been hampered by the lack of highly D3 receptor selective compounds that can be used in vivo. To address this problem, the potent and D3-receptor-selective antagonist NGB 2904 (1, 9H-fluorene-2-carboxylic acid 4-[(2,3-dichlorophenyl)-piperazin-1-yl]-butyl} amide, K-i (hD3) = 2.0 nM, K-i (hD2(L)) = 112 nM, D2/D3 selectivity ratio of 56) was chosen as a lead structure for chemical modification in an attempt to reduce its high lipophilicity (c log D = 6.94) while optimizing D3 receptor binding affinity and D2/D3 selectivity. A series of >30 novel analogues were synthesized, and their binding affinities were evaluated in competition binding assays in HEK 293 cells transfected with either D2(L), D3, or D4 human dopamine receptors using the high affinity, selective D2-like receptor antagonist I-125-IABN. Structural diversity in the aryl amide end of the molecule Was found to have a major influence on (sub)nanomolar D3 receptor affinity and D2/D3 selectivity, which was optimized using a more rigid trans-butenyl linker between the aryl amide and the piperazine. Several analogues demonstrated superior D3 receptor binding affinities and selectivities as compared to the parent ligand. Compound 29 (N-4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine- 2-yl-benzamide) displayed the most promising pharmacological profile (K-i (hD3) = 0.7 nM, K-i (hD2(L)) = 93.3 nM, D2/D3 selectivity ratio of 133). In addition, this ligand inhibited quinpirole stimulation of mitogenesis at human dopamine D3 receptors transfected into Chinese hamster ovary (CHO) cells, with an EC50 value of 3.0 nM. Compound 29 was a nearly 5 times more potent antagonist at the D3 receptor than 1 (EC50 = 14.4 nM). Moreover, a decrease in c log D value of similar to2 orders of magnitude was determined for this novel D3-receptor-preferring ligand, compared to 1. In summary, chemical modification of 1 has resulted in compounds with high affinity and selectivity for D3 receptors. The most promising candidate, compound 29, is currently being evaluated in animal models of cocaine abuse and will provide an important tool with which to elucidate the role of D3 receptors in drug reinforcement in vivo.
• Structurally rigid dopamine d3 receptor selective ligands and process for making them
  申请人：Newman Amy

  公开号：US20060106030A1

  公开（公告）日：2006-05-18

  A family of structurally rigid dopamine D3 receptor selective ligands is described. The family of structurally rigid dopamine D3 receptor selective ligands has the formula wherein A is cis or trans —CH═CH—, —C═C—, or cyclohexyl. B is cis or trans —CH═CH— or absent. R1 represents an optionally substituted phenyl group, wherein said substituents are selected from the group consisting of: hydrogen, halogen, amino, nitro, hydroxyl, alkoxy, alkyl, acyl and pyridyl, and said substitution may occur at any of the ortho, meta, or para positions, or R1 represents a heteroaromatic ring. A preferred heteroaromatic ring is indole, quinoxoline, pyridyl, pyrimidyl, or imidazole. R2 and R3 may be independently hydrogen or a halogen, or R2 alone may be C1, C2, or C3 alkoxy, and m is 1 or 2, and n is 0, 1, or 2.

  描述了一类结构刚性的多巴胺D3受体选择性配体家族。这个结构刚性的多巴胺D3受体选择性配体家族的公式如下：其中A是顺式或反式-CH═CH—，—C═C—或环己烷。B是顺式或反式-CH═CH—或缺失。R1代表一个可选择取代的苯基团，其中所述取代基选自以下组：氢、卤素、氨基、硝基、羟基、烷氧基、烷基、酰基和吡啶基，所述取代可以出现在邻位、间位或对位中的任何一个，或者R1代表一个杂环芳香环。首选的杂环芳香环是吲哚、喹喔啉、吡啶基、嘧啶基或咪唑基。R2和R3可以独立地是氢或卤素，或者R2单独可以是C1、C2或C3烷氧基，m为1或2，n为0、1或2。