title: 3-arylimino-2-indolones are potent and selective galanin GAL3 receptor antagonists.
abstract: A series of 3-imino-2-indolones are the first published, high-affinity antagonists of the galanin GAL3 receptor. One example, 1,3-dihydro-1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-2H-indol-2-one (9), was shown to have high affinity for the human GAL3 receptor (Ki=17 nM) and to be highly selective for GAL3 over a broad panel of targets, including GAL1 and GAL2. Compound 9 was also shown to be an antagonist in a human GAL3 receptor functional assay (Kb=29 nM).
authors.affiliation: Lundbeck Research USA, Inc., 215 College Road, Paramus, New Jersey 07652, USA. pacl@Lundbeck.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Konkel
authors.forename: Bharat
authors.initials: B
authors.lastname: Lagu
authors.forename: Lakmal W
authors.initials: LW
authors.lastname: Boteju
authors.forename: Hermogenes
authors.initials: H
authors.lastname: Jimenez
authors.forename: Stewart
authors.initials: S
authors.lastname: Noble
authors.forename: Mary W
authors.initials: MW
authors.lastname: Walker
authors.forename: Gamini
authors.initials: G
authors.lastname: Chandrasena
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Blackburn
authors.forename: Sham S
authors.initials: SS
authors.lastname: Nikam
authors.forename: Jon L
authors.initials: JL
authors.lastname: Wright
authors.forename: Brian E
authors.initials: BE
authors.lastname: Kornberg
authors.forename: Tracy
authors.initials: T
authors.lastname: Gregory
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Pugsley
authors.forename: Hyacinth
authors.initials: H
authors.lastname: Akunne
authors.forename: Kim
authors.initials: K
authors.lastname: Zoski
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Wise
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007097:Imines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008024:Ligands; D011869:Radioligand Assay; D051381:Rats; D044091:Receptor, Galanin, Type 1 / Q000187:drug effects; D044092:Receptor, Galanin, Type 2 / Q000187:drug effects; D044093:Receptor, Galanin, Type 3 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D007097:Imines; D007211:Indoles; D008024:Ligands; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D044093:Receptor, Galanin, Type 3; D000242:Cyclic AMP; C512433:1,3-dihydro-1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-2H-indol-2-one