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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Synthesis and structural investigation of some pyrimido(5,4-c)quinolin-4(3H)-one derivatives with a long-chain arylpiperazine moiety as potent 5-HT(1A/2A) and 5-HT(7) receptor ligands.
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Synthesis and structural investigation of some pyrimido(5,4-c)quinolin-4(3H)-one derivatives with a long-chain arylpiperazine moiety as potent 5-HT(1A/2A) and 5-HT(7) receptor ligands.

机译：具有长链芳基哌嗪部分作为有效的5-HT（1A / 2A）和5-HT（7）受体配体的一些嘧啶基（5,4-c）喹啉-4（3H）-one衍生物的合成和结构研究。

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摘要

A series of new pyrimido[5,4-c]quinolin-4(3H)-ones with variable length of the spacer between amide and 4-arylpiperazine moiety were prepared to further explore the role of a terminal portion in the serotonergic activity. The majority of compounds demonstrated high in vitro affinity for 5-HT(1A) receptor, and moderate-to-low affinity for 5-HT(2A) and 5-HT(7) receptors. X-ray analysis, two-dimensional NMR, conformational studies and docking into the 5-HT(1A) receptor model were conducted to investigate conformational preferences of selected 5-HT(1A) receptor ligands in different environments. The extended conformation of tetramethylene derivatives was found in a solid state, in DMSO (for a protonated form) and as a global energy minimum during conformational analysis in simulated water environment. Ligand geometry in top-scored complexes, obtained by docking to a set of 100 receptor models, were either fully extended or with central spacer torsion in synclinal conformation.
机译：制备一系列新的嘧啶并[5,4-c]喹啉-4（3H）-具有在酰胺和4-芳基哌嗪部分之间的间隔物的可变长度，以进一步探索末端部分在血清素能活性中的作用。大多数化合物对5-HT（1A）受体具有较高的体外亲和力，对5-HT（2A）和5-HT（7）受体具有中等至低的亲和力。进行了X射线分析，二维核磁共振，构象研究和对接到5-HT（1A）受体模型，以调查在不同环境中所选5-HT（1A）受体配体的构象偏好。在固态，DMSO（质子化形式）中发现了四亚甲基衍生物的扩展构象，并且在模拟水环境中进行构象分析时发现其总体能量最小值。通过对接至一组100个受体模型获得的得分最高的复合物中的配体几何形状完全延伸，或在向斜构象中带有中心间隔物扭转。

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