Synthesis and in vitro evaluation of N,N′-diphenyl and N-naphthyl-N′-phenylguanidines as N-methyl- -aspartate receptor ion-channel ligands

A series of N,N′-diphenyl and N-naphthyl-N′-phenyl guanidine derivatives was synthesized as potential N-methyl- -aspartate (NMDA) receptor positron emission tomography (PET) ligands. The affinity of the different compounds was determined using in vitro receptor binding assays, and their log P values were estimated using HPLC analysis. The effect of N′-3 and N′-3,5 substitution on affinity and lipophilicity was examined. The Kivalues ranged from 1.87 to 839 nM, while log P values between 1.22 and 2.88 were observed.