title: Novel imidazole-based histamine H3 antagonists.
abstract: A novel series of imidazole containing histamine H(3) receptor ligands were investigated and found to be potent functional antagonists. After improving the stability of these molecules towards liver microsomes, these compounds were found to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4-ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. jjablono@its.jnj.com
authors.forename: Jill A
authors.initials: JA
authors.lastname: Jablonowski
authors.forename: Kiev S
authors.initials: KS
authors.lastname: Ly
authors.forename: Michael
authors.initials: M
authors.lastname: Bogenstaetter
authors.forename: Curt A
authors.initials: CA
authors.lastname: Dvorak
authors.forename: Jamin D
authors.initials: JD
authors.lastname: Boggs
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Dvorak
authors.forename: Brian
authors.initials: B
authors.lastname: Lord
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Miller
authors.forename: Curt
authors.initials: C
authors.lastname: Mazur
authors.forename: Sandy J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008024:Ligands; D008956:Models, Chemical; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D054828:Histamine H3 Antagonists; D007093:Imidazoles; D008024:Ligands