title: Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
abstract: Extensive structural modification of immepyr (+)-2 led to the discovery of trans-4-methyl-3-imidazoyl pyrrolidine (+/-)-3a as a potent and highly selective H3 agonist. The pyrroline (+/-)-3a was resolved, and its (+) enantiomer, Sch 50971 [(+)-3a], showed a greater separation of H3 and H1 activities in vivo (H3/H1 ratio >> 330) than (R)-alpha-methylhistamine (+)-1 (H3/H1 ratio = 17), the standard H3 agonist.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute, Kenilworth, New Jersy 07033-0539, USA.
authors.forename: N Y
authors.initials: NY
authors.lastname: Shih
authors.forename: R
authors.initials: R
authors.lastname: Aslanian
authors.forename: A T
authors.initials: AT
authors.lastname: Lupo
authors.forename: S
authors.initials: S
authors.lastname: Orlando
authors.forename: J J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: M J
authors.initials: MJ
authors.lastname: Green
authors.forename: A K
authors.initials: AK
authors.lastname: Ganguly
authors.forename: R
authors.initials: R
authors.lastname: West
authors.forename: S
authors.initials: S
authors.lastname: Tozzi
authors.forename: W
authors.initials: W
authors.lastname: Kreutner
authors.forename: J A
authors.initials: JA
authors.lastname: Hey
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C116732:4-methyl-3-imidazoylpyrrolidine; D007093:Imidazoles; D011759:Pyrrolidines; D018100:Receptors, Histamine H3