Amino substituted analogs of 1-phenyl-3-phenylimino-2-indolones with potent galanin Gal3 receptor binding affinity and improved solubility.
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.
Konkel
Michael J
MJ
Lundbeck Research USA, Inc., 215 College Road, Paramus, NJ 07652, USA. PACL@Lundbeck.com
Packiarajan
Mathivanan
M
Chen
Heidi
H
Topiwala
Upendra P
UP
Jimenez
Hermogenes
H
Talisman
Ian Jamie
IJ
Coate
Heather
H
Walker
Mary W
MW
D000588:Amines / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D044093:Receptor, Galanin, Type 3 / Q000187:drug effects* / Q000378:metabolism; D012995:Solubility
D000588:Amines; D007211:Indoles; D044093:Receptor, Galanin, Type 3