GABAB-Agonistic Activity of Certain Baclofen Homologues

Molecules

Mohamed I. Attia²  Claus Herdeis¹ 

[1] Department of Pharmaceutical Chemistry, Institute of Pharmacy and Food Chemistry, Würzburg University, Am Hubland, Würzburg 97074, Germany;Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

关键词: GABA;    synthesis;    baclofen homologues;    GABA_B receptor agonists;    pharmacological evaluation;   

DOI  :  10.3390/molecules180910266

来源: mdpi

【 摘 要 】

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_BR 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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.