title: GABA(B)-agonistic activity of certain baclofen homologues.
abstract: 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.
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. mattia@ksu.edu.sa
authors: Mohamed I
authors: MI
authors: Attia
authors: Claus
authors: C
authors: Herdeis
authors: Hans
authors: H
authors: Bräuner-Osborne
mesh_terms: D001418:Baclofen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D058786:GABA-B Receptor Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D054879:Halogenation; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
chemical_list: D058786:GABA-B Receptor Agonists; D001418:Baclofen
references: Gastroenterology. 2000 Jan;118(1):7-13
references: 10611148
references: Am J Hosp Palliat Care. 2009 Apr-May;26(2):112-8
references: 19114602
references: J Med Chem. 2001 May 24;44(11):1827-32
references: 11356116
references: J Med Chem. 2001 Jan 4;44(1):27-35
references: 11141085
references: Pflugers Arch. 1994 May;427(1-2):136-42
references: 8058462
references: Br J Urol. 1979 Dec;51(6):504-5
references: 394795
references: J Med Chem. 1993 Apr 16;36(8):1041-7
references: 8386770
references: Eur J Pharmacol. 2001 Apr 13;417(3):177-80
references: 11334848
references: Br J Pharmacol. 1999 Dec;128(7):1370-4
references: 10602314
references: J Med Chem. 1991 Aug;34(8):2557-60
references: 1652022
references: J Med Chem. 1999 Jun 3;42(11):2053-9
references: 10354414
references: Br J Pharmacol. 1982 Sep;77(1):163-8
references: 6289954
references: Nature. 1998 Dec 17;396(6712):683-7
references: 9872317
references: Nature. 1993 May 20;363(6426):274-6
references: 8387644
references: Adv Pharmacol. 2010;58:373-96
references: 20655489
references: Angew Chem Int Ed Engl. 2001 Dec 3;40(23):4445-4447
references: 12404440
references: Bioorg Med Chem Lett. 2011 Nov 1;21(21):6582-5
references: 21920749
references: Drugs. 1974;8(1):1-14
references: 4154834