3-arylimino-2-indolones are potent and selective galanin GAL3 receptor antagonists.
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).
Konkel
Michael J
MJ
Lundbeck Research USA, Inc., 215 College Road, Paramus, New Jersey 07652, USA. pacl@Lundbeck.com
Lagu
Bharat
B
Boteju
Lakmal W
LW
Jimenez
Hermogenes
H
Noble
Stewart
S
Walker
Mary W
MW
Chandrasena
Gamini
G
Blackburn
Thomas P
TP
Nikam
Sham S
SS
Wright
Jon L
JL
Kornberg
Brian E
BE
Gregory
Tracy
T
Pugsley
Thomas A
TA
Akunne
Hyacinth
H
Zoski
Kim
K
Wise
Lawrence D
LD
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
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