Synthesis and in vitro Receptor Binding Assay of Pyrazolo[1,5-α]pyridines

doi:10.3724/SP.J.1095.2014.30428

Chinese Journal of Applied Chemistry

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Synthesis and in vitro Receptor Binding Assay of Pyrazolo[1,5-α]pyridines

LI Gucai^*, SUN Lei, CHEN Bo, ZHONG Huaiyu

(College of Chemistry and Chemical Engineering,Hunan Institute of Engineering,Xiangtan 411104,China)

Received:2013-08-26 Revised:2013-10-20 Published:2014-06-10 Online:2014-06-10

Abstract

Abstract: 3-(4-Benzylpiperazin-1-ylmethyl)pyrazolo[1,5-α]pyridine, 3-[4-(4-chlorobenzyl) piperazin-1-ylmethyl]pyrazolo-[1,5-α]pyridine and 3-[4-(4-methoxybenzyl)piperazin-1-ylmethyl] pyrazolo[1,5-a]pyridine were synthesized from pyrazolo[1,5-α]pyridine-3-carbaldehyde and 1-piperazinearboxaldehyde through reductive amination, amide hydrolysis and N-alkylation. The structures of the intermediates and the target compounds were confirmed by 1H NMR and ESI MS. Through in vitro receptor binding assay, the affinity constants(Ki) of the target compounds were determined to be 1.6, 7.2, 65 nmol/L for D4 receptor; 1920, 5320, 9800 nmol/L for D2 receptor; 1710, 4270 and 5600 nmol/L for dopamine D3 receptor, respectively. The results suggested that 3-(4-benzylpiperazin-1-ylmethyl)pyrazolo[1,5-α] pyridine is a potential dopamine D4 receptor ligand.

Key words: pyrazolo[1,5-&, alpha, ]pyridine, dopamine D4 receptor, ligand, in vitro receptor binding assay

CLC Number:

O626

LI Gucai*, SUN Lei, CHEN Bo, ZHONG Huaiyu. Synthesis and in vitro Receptor Binding Assay of Pyrazolo[1,5-α]pyridines[J]. Chinese Journal of Applied Chemistry, DOI: 10.3724/SP.J.1095.2014.30428.

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Synthesis and in vitro Receptor Binding Assay of Pyrazolo[1,5-α]pyridines

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