title: Synthesis and SAR of aminoalkoxy-biaryl-4-carboxamides: novel and selective histamine H3 receptor antagonists.
abstract: Novel 4'-[(NR1R2-1-yl)]-propoxy-biaryl-4-carboxamides were designed and synthesized. All compounds were tested for affinity at histamine H(3)receptors. Most compounds were highly potent and selective for human and rat H(3) receptors and selected examples such as A-349821 showed functional antagonism of H(3) receptors in vitro and in a mouse dipsogenia model.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park 60064-6123, USA. ramin.fagih@abbott.com
authors.forename: Ramin
authors.initials: R
authors.lastname: Faghih
authors.forename: Wesley
authors.initials: W
authors.lastname: Dwight
authors.forename: Jia Bao
authors.initials: JB
authors.lastname: Pan
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Fox
authors.forename: Kathy M
authors.initials: KM
authors.lastname: Krueger
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Esbenshade
authors.forename: Jill M
authors.initials: JM
authors.lastname: McVey
authors.forename: Kennan
authors.initials: K
authors.lastname: Marsh
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Hancock
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D000882:Haplorhini; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D011869:Radioligand Assay; D051381:Rats; D017982:Receptors, Biogenic Amine / Q000187:drug effects / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000588:Amines; D006633:Histamine Antagonists; D017982:Receptors, Biogenic Amine; D018100:Receptors, Histamine H3