Discovery of a novel potent GABAB receptor agonist

Abstract Structure–activity studies have led to a discovery of 3-(4-pyridyl)methyl ether derivative 9d that has 25- to 50-fold greater functional potency than R-baclofen at human and rodent GABA B receptors in vitro. Mouse hypothermia studies confirm that this compound crosses the blood–brain barrier and is approximately 50-fold more potent after systemic administration.