Potential anxiolytic agents. 2. Improvement of oral efficacy for the pyrido[1,2-a]benzimidazole (PBI) class of GABA-A receptor modulators

We have further explored the structure-activity relationships of pyrido[1,2-a]benzimidazole (PBI) derivatives (viz. prototype 1), a novel series of central GABA-A receptor modulators, with the intent of enhancing oral efficacy. A study involving the introduction of acidic or basic groups led to the identification of RWJ-38293 (3a) as a potential anxiolytic agent.