title: A new family of H3 receptor antagonists based on the natural product Conessine.
abstract: A new family of Histamine H(3) receptor antagonists (5a-t) has been prepared based on the structure of the natural product Conessine, a known H(3) antagonist. Several members of the new series are highly potent and selective binders of rat and human H(3) receptors and display inverse agonism at the human H(3) receptor. Compound 5n exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H(3) receptor in an in-vivo pharmacological model.
authors.affiliation: Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Santora
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Covel
authors.forename: Rena
authors.initials: R
authors.lastname: Hayashi
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Hofilena
authors.forename: Jason B
authors.initials: JB
authors.lastname: Ibarra
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Pulley
authors.forename: Michael I
authors.initials: MI
authors.lastname: Weinhouse
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Sengupta
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Duffield
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
authors.forename: Robert R
authors.initials: RR
authors.lastname: Webb
authors.forename: Carleton
authors.initials: C
authors.lastname: Sage
authors.forename: Albert
authors.initials: A
authors.lastname: Ren
authors.forename: Guilherme
authors.initials: G
authors.lastname: Pereira
authors.forename: Jens
authors.initials: J
authors.lastname: Knudsen
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Edwards
authors.forename: Marissa
authors.initials: M
authors.lastname: Suarez
authors.forename: John
authors.initials: J
authors.lastname: Frazer
authors.forename: William
authors.initials: W
authors.lastname: Thomsen
authors.forename: Erin
authors.initials: E
authors.lastname: Hauser
authors.forename: Kevin
authors.initials: K
authors.lastname: Whelan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Grottick
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D017442:Histamine Agonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000588:Amines; D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; C007111:conessine