title: D-amino acid homopiperazine amides: discovery of A-320436, a potent and selective non-imidazole histamine H(3)-receptor antagonist.
abstract: Structure-activity relationships of homopiperazine-containing alkoxybiaryl nitriles employing various D-amino acid moieties and their N-furanoyl analogues were undertaken. This led to A-320436, a potent and selective non-imidazole H(3)-receptor antagonist possessing balanced affinity for both rat and human H(3)-receptors. This compound was shown to demonstrate in vitro and in vivo functional antagonism and is non-neurotoxic at doses (i.p.) up to 163 mg/kg in a general observation test.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. michael.curtis@abbott.com
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curtis
authors.forename: Wesley
authors.initials: W
authors.lastname: Dwight
authors.forename: John
authors.initials: J
authors.lastname: Pratt
authors.forename: Marlon
authors.initials: M
authors.lastname: Cowart
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Esbenshade
authors.forename: Kathy M
authors.initials: KM
authors.lastname: Krueger
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Fox
authors.forename: Jia Bao
authors.initials: JB
authors.lastname: Pan
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Pagano
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Hancock
authors.forename: Ramin
authors.initials: R
authors.lastname: Faghih
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D006633:Histamine Antagonists; D010879:Piperazines; D018100:Receptors, Histamine H3