2-[4-(4-氟苄基)哌嗪-1-基甲基]吡唑并[1,5-a]吡啶的合成及其体外受体结合分析

以吡唑并[1,5-a]吡啶-2-甲醛和N-甲酰基哌嗪为原料,经过还原胺化反应、水解反应、N-烷基化反应,合成了2-[4-(4-氟苄基)哌嗪-1-基甲基]吡唑并[1,5-a]吡啶,总收率29.5%,用1HNMR、19FNMR、ESI-MS对中间体及目标化合物进行了结构表征,并通过体外受体结合实验,测定目标化合物对多巴胺D4受体的亲和常数为1.2nmol/L,对D2、D3受体的亲和常数分别为3 900、1 890 nmol/L,显示对多巴胺D4受体具有较高的亲和性与选择性,是一种潜在的多巴胺D4受体配基。

Synthesis of 2-[4-(4-Fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine and Its in vitro Receptor Binding Assay

2-[4-(4-Fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine was synthesized from pyrazolo[1,5-a]pyridine-2-carbaldehyde and 1-piperazinearboxaldehyde through reductive amination, amide hydrosis and N-alkylation. The structures of the intermediates and the target compound were confirmed by 1H NMR, 19F NMR and ESI- MS. Through in vitro receptor binding assay, the affinity constants of the target compound were determined to be 1.2, 3900 and 1890 nM for D4, D2, D3 receptor, respectively. It indicated that 2-[4-(4-fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine is a potential dopamine D4 receptor ligand.