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

Authors: Cole DC, Gross JL, Comery TA, Aschmies S, Hirst WD, Kelley C, Kim JI, Kubek K, Ning X, Platt BJ, Robichaud AJ, Solvibile WR, Stock JR, Tawa G, Williams MJ, Ellingboe JW.
Publisher/Year: Bioorg Med Chem Lett. 2010 Feb 1;20(3):1237-40. Epub 2009 Dec 4.
Pub Med ID/Journal ID: PMID:20042333


Using a focused screen of biogenic amine compounds we identified a novel series of H(3)R 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. Copyright (c) 2009 Elsevier Ltd. All rights reserved.