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, 49 (8), 2600-10

A Pyridazine Series of alpha2/alpha3 Subtype Selective GABA A Agonists for the Treatment of Anxiety

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A Pyridazine Series of alpha2/alpha3 Subtype Selective GABA A Agonists for the Treatment of Anxiety

Richard T Lewis et al. J Med Chem.

Abstract

The development of a series of GABA(A) alpha2/alpha3 subtype selective pyridazine based benzodiazepine site agonists as anxiolytic agents with reduced sedative/ataxic potential is described, including the discovery of 16, a remarkably alpha3-selective compound ideal for in vivo study. These ligands are antagonists at the alpha1 subtype, with good CNS penetration and receptor occupancy, and excellent oral bioavailability.

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