title: Synthesis and evaluation of potent pyrrolidine H(3) antagonists.
abstract: The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable, to afford several compounds with high affinity and selectivity for the H(3) receptor.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60031, USA. anil.vasudevan@abbott.com
authors.forename: Anil
authors.initials: A
authors.lastname: Vasudevan
authors.forename: Scott E
authors.initials: SE
authors.lastname: Conner
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gentles
authors.forename: Ramin
authors.initials: R
authors.lastname: Faghih
authors.forename: Huaqing
authors.initials: H
authors.lastname: Liu
authors.forename: Wesley
authors.initials: W
authors.lastname: Dwight
authors.forename: Lynne
authors.initials: L
authors.lastname: Ireland
authors.forename: Chae Hee
authors.initials: CH
authors.lastname: Kang
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Esbenshade
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Hancock
mesh_terms: D000215:Acylation; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D006633:Histamine Antagonists; D008024:Ligands; D011759:Pyrrolidines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3