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[摘要]：Understanding the role of GABA(C) receptors in the central nervous system is limited due to a lack of specific ligands. Novel gamma-aminobutyric acid (GABA) analogues based on 3-(aminomethyl)-1-oxo-1-hydroxy-phospholane 17 and 3-(guanido)-1-oxo-1-hydroxy-phospholane 19 were investigated to obtain selective GABA(C) receptor antagonists. A compound of high potency (19, K-B = 10 mu M) and selectivity (greater than 100 times at rho(1) GABA(C) receptors as compared to alpha(1)beta(2)gamma(2L) GABA(A) and GABA(B(1b,2)) receptors) was obtained. The cyclic phosphinic acids (17 and 19) are novel lead agents for developing into more potent and selective GABA(C) receptor antagonists with increased lipophilicity for future in vivo studies. |
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