Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Molecules. 2013 Aug 22;18(9):10266-84. doi: 10.3390/molecules180910266.
Baclofen (1) is a potent and selective agonist for bicuculline-insensitive GABA(B) receptors and is used clinically as an antispastic and muscle relaxant agent. In the search for new bioactive chemical entities that bind specifically to GABA(B) receptors, we report here the synthesis of certain baclofen homologues, namely (R,S)-5-amino-3-arylpentanoic acid hydrochlorides (R,S)-1a-h as well as (R,S)-5-amino-3-methylpentanoic acid [(RS)-1i] to be evaluated as GABA(B)R agonists. Compound 1a is an agonist to GABA(B) receptors with an EC₅₀ value of 46 μM on tsA201 cells transfected with GABA(B1b)/GABA(B2)/Gqz5, being the most active congener among all the synthesized compounds.
巴氯芬（1）是一种高效且选择性的双环己基吲哚非敏感 GABA（B）受体激动剂，临床上用作抗痉挛和肌肉松弛剂。在寻找与 GABA（B）受体特异性结合的新型生物活性化学实体的过程中，我们在此报告了某些巴氯芬类似物的合成，即（R，S）-5-氨基-3-芳基戊酸盐酸盐（R，S）-1a-h 以及（R，S）-5-氨基-3-甲基戊酸[（RS）-1i]，将其作为 GABA（B）R 激动剂进行评估。化合物 1a 是一种 GABA（B）受体激动剂，在转染 GABA（B1b）/GABA（B2）/Gqz5 的 tsA201 细胞上的 EC₅₀值为 46 μM，是所有合成化合物中最活跃的同系物。
