喹唑酮类甘氨酸转运体1抑制剂的设计、合成及药理活性研究

Design,synthesis and in vitro activity of quinazolone glycine transporter-1 inhibitors

摘要: 甘氨酸转运体1（GlyT1）是研究抗精神分裂症药物的靶点。以化合物2,4-二氯-N-4-（环丙甲基）-1-（乙磺酰基）哌啶-4-基甲基苯甲酰胺（ 1a ，IC₅₀=92.2 nmol/L）为参考，设计并合成了未见文献报道的13个喹唑啉酮类化合物。初步药理活性实验结果表明，所合成的化合物除化合物 7e 外都具有一定程度的GlyT1抑制活性，其中化合物 7j 的活性最强，接近阳性对照药 1a 。

Abstract: Glycine transporter-1 (GlyT1) is an attractive therapeutic target for schizophrenia.A series of novel quinazolone derivatives were designed and synthesized as active GlyT1 inhibitors on the basis of compound 2,4-dichloro-N-4-(cyclopropylmethyl)-1-(ethylsulfonyl)piperidin-4-ylmethylbenzamide( 1a ,IC₅₀=92.2 nmol/L)developed by Merck & Co Inc.Preliminary results showed that all the compounds except 7e possessed GlyT1 inhibitory activity to a different extent,and that compound 7j was the most potent one within this series of compounds,possessing almost the same potency as that of compound 1a .