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

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

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。

2-[ 4-（4-Fluorobenzyl） piperazin-l-ylmethyl] pyrazolo[ 1,5-a] pyridine was synthesized from pyrazolo[ 1,5-a] pyridine-2-carbaldehyde and 1-piperazineearboxaldehyde through reductive amination, amide hydrosis and N-alkylation. The structures of the intermediates and the target compound were confirmed by ^1HNMR,^19 FNMR and ESI-MS. Through in vitro receptor binding assay, the affinity constants of the target compound were determined to be 1.2,3 900 and 1 890 nmo]/L for D4, D2, and D3 receptor, respectively, which indicates that 2- [ 4- （4-fluorobenzyl） piperazin-1 -ylmethyl ] pyrazolo [ 1, 5-a ] pyridine is a potential dopamine D4 receptor ligand.