Structure-Affinity Relationship Study on N-(4-(4-Arylpiperazin-1-yl)butyl)arylcarboxamides as Potent and Selective Dopamine D(3) Receptor Ligands.

Leopoldo M; Berardi F; Colabufo NA; De Giorgio P; Lacivita E; Perrone R; Tortorella V

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Structure-Affinity Relationship Study on N-(4-(4-Arylpiperazin-1-yl)butyl)arylcarboxamides as Potent and Selective Dopamine D(3) Receptor Ligands.

机译：N-（4-（4-芳基哌嗪-1-基）丁基）芳基羧酰胺作为强效和选择性多巴胺D（3）受体配体的结构亲和关系研究。

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The benzamide PB12 (N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide) (1), already reported as potent and selective dopamine D(4) receptor ligand, has been modified searching for structural features that could lead to D(3) receptor affinity. Changes in the aromatic ring linked to N-1 piperazine ring led to the identification of 2-methoxyphenyl and 2,3-dichlorophenyl derivatives (compounds 6 and 13) displaying moderate D(3) affinity (K(i) = 145 and 31 nM, respectively). Intermediate alkyl chain elongation in compounds 1, 6, and 13 improved binding affinity for the D(3) receptor and decreased the D(4) affinity (compounds 18-26). Among these latter compounds, the N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-3-methoxybenzamide (19) was further modified with the replacement or of the 2,3-dichlorophenyl moiety (compounds 27-30) or of the 3-methoxyphenyl ring (compounds 31-41). In this way, we identified several high-affinity D(3) ligands (0.13 nM < K(i)'s < 4.97 nM) endowed with high selectivity over D(2), D(4), 5-HT(1A), and alpha(1) receptors. In addition, N-[4-[4-(2,3-dimethylphenyl)piperazin-1-yl]butyl]-3-methoxybenzamide (27) and N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofuranca rboxamide (41) appear to be valuable candidates for positron emission tomography (PET) because of their affinity values, lipophilicity properties, and liability of (11)C labeling in the O-methyl position.

机译：苯甲酰胺PB12（N- [2- [4-（4-氯苯基）哌嗪-1-基]乙基] -3-甲氧基苯甲酰胺）（1）已被报告为有效的和选择性的多巴胺D（4）受体配体。修改搜索可能导致D（3）受体亲和力的结构特征。与N-1哌嗪环相连的芳环的变化导致鉴定出具有中等D（3）亲和力（K（i）= 145和31 nM的2-甲氧基苯基和2,3-二氯苯基衍生物（化合物6和13），分别）。化合物1、6和13中的中间烷基链延长改善了对D（3）受体的结合亲和力，并降低了D（4）亲和力（化合物18-26）。在这些后面的化合物中，N- [4- [4-（2,3-二氯苯基）哌嗪-1-基]丁基] -3-甲氧基苯甲酰胺（19）用2,3-二氯苯基取代或进一步改性。部分（化合物27-30）或3-甲氧基苯基环（化合物31-41）。通过这种方法，我们确定了几个高亲和力D（3）配体（0.13 nM

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来源
《Journal of Medicinal Chemistry》 |2002年第26期|共9页
作者
Leopoldo M; Berardi F; Colabufo NA; De Giorgio P; Lacivita E; Perrone R; Tortorella V;
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正文语种 eng
中图分类药学;
关键词
receptor; Nanomole/liter; 3-methoxybenzamide;

机译：受体;纳莫诺尔/升;3-甲氧基苯甲酰胺;

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1. Structure-Affinity Relationship Study on N-(4-(4-Arylpiperazin-1-yl)butyl)arylcarboxamides as Potent and Selective Dopamine D(3) Receptor Ligands. [J] . Leopoldo M, Berardi F, Colabufo NA, Journal of Medicinal Chemistry . 2002,第26期

机译：N-（4-（4-芳基哌嗪-1-基）丁基）芳基羧酰胺作为强效和选择性多巴胺D（3）受体配体的结构亲和关系研究。
2. Synthesis and binding profile of constrained analogues of N-(4-(4-arylpiperazin-1-yl)butyl)-3-methoxybenzamides, a class of potent dopamine D3 receptor ligands. [J] . Leopoldo M, Lacivita E, Colabufo NA, Journal of Pharmacy and Pharmacology . 2006,第2期

机译：N-（4-（4-芳基哌嗪-1-基）丁基）-3-甲氧基苯甲酰胺（一种有效的多巴胺D3受体配体）的受约束类似物的合成和结合特征。
3. 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 [J] . Grundt P, Carlson EE, Cao JJ, Journal of Medicinal Chemistry . 2005,第3期

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7. Heterocyclic Analogues of N-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butyl)arylcarboxamides with Functionalized Linking Chains as Novel Dopamine D3 Receptor Ligands: Potential Substance Abuse Therapeutic Agents [O] . -1

机译：N-（4-（2,3-（4-二氯苯基）哌嗪-1-基）丁基）芳基甲酰酰胺的杂环类似物，其具有官能化连接链作为新型多巴胺D3受体配体：潜在的药物滥用治疗剂

Structure-Affinity Relationship Study on N-(4-(4-Arylpiperazin-1-yl)butyl)arylcarboxamides as Potent and Selective Dopamine D(3) Receptor Ligands.

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