| Title | Synthesis and biological evaluation of 4-fluoroproline and 4-fluoropyrrolidine-2-acetic acid derivatives as new GABA uptake inhibitors. | | Author(s) | Zhuang W, Zhao X, Zhao G, Guo L, Lian Y, Zhou J, Fang D | | Institution | Fujian Institute of Microbiology, No. 25, Jinbu road, Fuzhou 350007, China. | | Source | Bioorg Med Chem 2009 Aug 9. | | Abstract | Preparation for the N-alkylated derivatives of enantiomerically pure (2S)-4-fluoroproline and (2S)-4-fluoropyrrolidine-2-acetic acid is described. The final compounds were evaluated as potential GAT-1 uptake inhibitors via cultured cell lines expressing mouse GAT-1. Compared with their corresponding 4-hydroxy compounds, these derivatives exhibited slight improvement on their inhibitory potency, but still much weaker than their corresponding compounds with no substituents at the C-4 of the pyrrolidine moiety, with the most potent affinity being about 1/15 fold as that of Tiagabine. The drastic decrease of their affinity may arise from sharp reduction of their basicity due to strong inductive effect of the 4-fluorine. However the configuration of the C-4 linking fluorine did not have much influence on their affinity for GAT-1. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19703775 |
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