Benzimidazole- and indole-substituted 1,3′-bipyrrolidine benzamides as histamine H3 receptor antagonists

Using a focused screen of biogenic amine compounds we identified a novel series of H3R antagonists. A preliminary SAR study led to reduction of MW while increasing binding affinity and potency. Optimization of the physical properties of the series led to (S)-6n, with improved brain to plasma exposure and efficacy in both water intake and novel object recognition models.