title: Benzimidazole- and indole-substituted 1,3'-bipyrrolidine benzamides as histamine H3 receptor antagonists.
abstract: 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.
authors.affiliation: Chemical Sciences, Wyeth Research, 401 N Middletown Rd. Pearl River, NY 10965, United States. coledc@wyeth.com
authors.forename: Derek C
authors.initials: DC
authors.lastname: Cole
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Gross
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Comery
authors.forename: Suzan
authors.initials: S
authors.lastname: Aschmies
authors.forename: Warren D
authors.initials: WD
authors.lastname: Hirst
authors.forename: Cody
authors.initials: C
authors.lastname: Kelley
authors.forename: Ji-In
authors.initials: JI
authors.lastname: Kim
authors.forename: Katie
authors.initials: K
authors.lastname: Kubek
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ning
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Platt
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Robichaud
authors.forename: William R
authors.initials: WR
authors.lastname: Solvibile
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Stock
authors.forename: Gregory
authors.initials: G
authors.lastname: Tawa
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Williams
authors.forename: John W
authors.initials: JW
authors.lastname: Ellingboe
mesh_terms: D000818:Animals; D001549:Benzamides / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D001562:Benzimidazoles / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D018938:Caco-2 Cells; D002460:Cell Line; D054828:Histamine H3 Antagonists / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011759:Pyrrolidines / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D018100:Receptors, Histamine H3 / Q000097:blood / Q000378:metabolism
chemical_list: D001549:Benzamides; D001562:Benzimidazoles; D054828:Histamine H3 Antagonists; D007211:Indoles; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; C031000:benzimidazole