Synthesis and in vitro evaluation of N,N'-diphenyl and N-naphthyl-N'-phenylguanidines as N-methyl-D-aspartate receptor ion-channel ligands.
A series of N,N'-diphenyl and N-naphthyl-N'-phenyl guanidine derivatives was synthesized as potential N-methyl-D-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 K(i) values ranged from 1.87 to 839nM, while log P values between 1.22 and 2.88 were observed.
Dumont
Filip
F
Division of Functional Brain Mapping, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA. filip.dumont@rug.ac.be
Sultana
Abida
A
Waterhouse
Rikki N
RN
D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D006146:Guanidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D014055:Tomography, Emission-Computed
D006146:Guanidines; D016194:Receptors, N-Methyl-D-Aspartate; C026943:phenylguanidine