title: Amino substituted analogs of 1-phenyl-3-phenylimino-2-indolones with potent galanin Gal3 receptor binding affinity and improved solubility.
abstract: A series of amino analogs of 1,3-dihydro-1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-2H-indol-2-one (1) were synthesized to improve aqueous solubility, while retaining high affinity for the human galanin Gal3 receptor. A very potent analog (9e, 1,3-dihydro-1-[3-(2-pyrrolidinylethoxy)phenyl]-3-[[3-(trifluoromethyl)phenyl]imino]-2H-indol-2-one, Ki=5 nM) shows good selectivity and solubility of 48 microg/mL at pH 7.4.
authors.affiliation: Lundbeck Research USA, Inc., 215 College Road, Paramus, NJ 07652, USA. PACL@Lundbeck.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Konkel
authors.forename: Mathivanan
authors.initials: M
authors.lastname: Packiarajan
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.forename: Upendra P
authors.initials: UP
authors.lastname: Topiwala
authors.forename: Hermogenes
authors.initials: H
authors.lastname: Jimenez
authors.forename: Ian Jamie
authors.initials: IJ
authors.lastname: Talisman
authors.forename: Heather
authors.initials: H
authors.lastname: Coate
authors.forename: Mary W
authors.initials: MW
authors.lastname: Walker
mesh_terms: D000588:Amines / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D044093:Receptor, Galanin, Type 3 / Q000187:drug effects* / Q000378:metabolism; D012995:Solubility
chemical_list: D000588:Amines; D007211:Indoles; D044093:Receptor, Galanin, Type 3