Amino substituted analogs of 1-phenyl-3-phenylimino-2-indolones with potent galanin Gal sub(3) 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 Gal sub(3) receptor. A very potent analog (9e, 1,3-dihydro-1-[3-(2- pyrrolidinylethoxy)phenyl]-3-[[3-(trifluoromethyl)phenyl]imino]-2H -indo l-2- one, K sub(i) = 5 nM) shows good selectivity and solubility of 48 mu g/mL at pH 7.4.