Structure-intrinsic activity relationship studies in the group of 1-imido/amido substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives; new, potent 5-HT1A receptor agents with anxiolytic- like activity.

Bojarski AJ; Paluchowska MH; Duszynska B; Bugno R; Klodzinska A; Tatarczynska E; Chojnacka Wojcik E

首页> 外文期刊>Bioorganic and medicinal chemistry >Structure-intrinsic activity relationship studies in the group of 1-imido/amido substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives; new, potent 5-HT1A receptor agents with anxiolytic- like activity.

【24h】

Structure-intrinsic activity relationship studies in the group of 1-imido/amido substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives; new, potent 5-HT1A receptor agents with anxiolytic- like activity.

机译：1-酰亚胺/酰胺基取代的4-（4-芳基哌嗪-1-基）环己烷衍生物的结构-本征活性关系研究;具有抗焦虑活性的新型有效5-HT1A受体药物。

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

Introduction of 1,4-disubstituted cyclohexane ring in the structure of flexible long chain arylpiperazines resulted in linearly constrained, potent serotonin (5-HT)(1A) ligands. In order to trace structure-intrinsic activity relationships in this group, a new series of 1-substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives with different cyclic imide/amide termini, and their flexible, tetramethylene analogues were synthesized and pharmacologically evaluated for 5-HT(1A) receptors. In vitro binding experiments revealed that all the compounds were potent 5-HT(1A) receptor agents (K(i) = 1.9-74 nM). Some derivatives tested additionally showed also high affinity for alpha(1)-adrenergic receptors (K(i) = 2.9-101 nM) and for 5-HT(7) receptors. Functional in vivo examination revealed that rigid ligands with o-OCH(3) group in the aryl moiety and cyclic imide system in the opposite terminal behaved like postsynaptic 5-HT(1A) receptor antagonists. On the other hand, unsubstituted, m-Cl, or m-CF(3) substituted derivatives as well as those with cyclic amide group in the terminal fragment exhibited agonistic or partial agonistic activity. Three out of four derivatives tested, that is, postsynaptic 5-HT(1A) antagonists 9 and 10, and partial agonist 16, showed anxiolytic-like activity in the conflict drinking (Vogel) test in rats.

机译：在柔性长链芳基哌嗪的结构中引入1,4-二取代的环己烷环导致线性约束的有效血清素（5-HT）（1A）配体。为了追踪该组中的结构-本征活性关系，合成了具有不同环酰亚胺/酰胺末端的一系列新的1-取代的4-（4-芳基哌嗪-1-基）环己烷衍生物，以及它们的柔性四亚甲基类似物，对5-HT（1A）受体进行药理评估。体外结合实验表明，所有化合物均为有效的5-HT（1A）受体试剂（K（i）= 1.9-74 nM）。另外测试的一些衍生物还显示出对α（1）-肾上腺素受体（K（i）= 2.9-101 nM）和5-HT（7）受体的高亲和力。体内功能检查发现，刚性配体的芳基部分带有o-OCH（3），相反端的环状酰亚胺系统的行为类似于突触后5-HT（1A）受体拮抗剂。另一方面，未取代的，m-Cl或m-CF（3）取代的衍生物以及在末端片段中具有环状酰胺基的衍生物表现出激动或部分激动活性。测试的四个衍生物中的三个，即突触后5-HT（1A）拮抗剂9和10和部分激动剂16，在大鼠的冲突饮酒（Vogel）试验中显示出类似抗焦虑的活性。

著录项

来源
《Bioorganic and medicinal chemistry》 |2006年第5期|共12页
作者
Bojarski AJ; Paluchowska MH; Duszynska B; Bugno R; Klodzinska A; Tatarczynska E; Chojnacka Wojcik E;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类基础医学;
关键词
derivatives; serotonin 1A receptor; Serotonin; Cyclohexanes; Anti-Anxiety Agents; 血清素; 环己烷类; 抗焦虑药;

机译：derivatives;serotonin 1A receptor;Serotonin;Cyclohexanes;Anti-Anxiety Agents;血清素;环己烷类;抗焦虑药;

相似文献

外文文献
中文文献
专利

1. Structure-intrinsic activity relationship studies in the group of 1-imido/amido substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives; new, potent 5-HT1A receptor agents with anxiolytic- like activity. [J] . Bojarski AJ, Paluchowska MH, Duszynska B, Bioorganic and medicinal chemistry . 2006,第5期

机译：1-酰亚胺/酰胺基取代的4-（4-芳基哌嗪-1-基）环己烷衍生物的结构-本征活性关系研究;具有抗焦虑活性的新型有效5-HT1A受体药物。
2. First structure-activity relationship study on dopamine D-3 receptor agents with N-[4-(4-arylpiperazin-1-yl)butyl]-arylcarboxamide structure [J] . Leopoldo M, Lacivita E, Colabufo NA, Journal of Medicinal Chemistry . 2005,第25期

机译：具有N- [4-（4-芳基哌嗪-1-基）丁基]-芳基甲酰胺结构的多巴胺D-3受体药物的第一构效关系研究
3. 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。
4. Synthesis of new glutamate receptor probes: I. Total synthesis of dysiherbaine, a potent glutamate receptor excitotoxin; II. Design and synthesis of dysiherbaine analogues; III. Synthesis and structure-activity relationships of substituted benzothiadiazides and their role as AMPA receptor modulators. [D] . Phillips, Dean Paul. 2001

机译：新型谷氨酸受体探针的合成：I. dysiherbaine的全合成，一种有效的谷氨酸受体兴奋性毒素；二。 dysiherbaine类似物的设计和合成；三，取代的苯并噻二叠氮化物的合成及其构效关系及其作为AMPA受体调节剂的作用。
5. Synthesis Docking Studies and Biological Evaluation of Benzobthiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one Derivatives on 5-HT1A Serotonin Receptors [O] . Hernán Pessoa-Mahana, Gonzalo Recabarren-Gajardo, Jenny Fiedler Temer, 2012

机译：5-HT1A 5-羟色胺受体的苯并b噻吩-2-基-3-（4-芳基哌嗪-1-基）-丙烷-1-酮衍生物的合成对接研究和生物学评价
6. Synthesis, Docking Studies and Biological Evaluation of Benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one Derivatives on 5-HT1A Serotonin Receptors [O] . Ramiro Araya-Maturana, Claudio Saitz Barría, Gerald Zapata-Torres, 2012

机译：苯并[b]噻吩-2-基-3-（4-芳基哌嗪-1-基） - 丙-1-酮衍生物在5-HT1a 5-羟色胺受体上的合成，对接研究和生物学评价

Structure-intrinsic activity relationship studies in the group of 1-imido/amido substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives; new, potent 5-HT1A receptor agents with anxiolytic- like activity.

摘要

著录项

相似文献

相关主题

期刊订阅