Synthesis and in vitro evaluation of (18)F-labelled S-fluoroalkyl diarylguanidines: Novel high-affinity NMDA receptor antagonists for imaging with PET.
Two S-[(18)F]fluoroalkylated diarylguanidines were synthesized and evaluated in vitro as potential tracers for imaging of N-methyl-d-aspartate receptors (NMDARs) with positron emission tomography (PET). [(18)F]1 and [(18)F]10 were synthesized by [(18)F]fluoroethylation and [(18)F]fluoromethylation of the thiol precursor 6, respectively. [(18)F]1 is a promising candidate NMDAR PET tracer, with low nanomolar affinity for the NMDA PCP-site, high selectivity and moderate lipophilicity.
GE Healthcare MDx Research, MRC Cyclotron Building, Hammersmith Hospital, London W12 0NN, United Kingdom.
Edward G
EG
Robins
Yongjun
Y
Zhao
Imtiaz
I
Khan
Anthony
A
Wilson
Sajinder K
SK
Luthra
Erik
E
Rstad
D000818:Animals; D001665:Binding Sites; D005462:Fluorine Radioisotopes; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry
C468267:CNS 5161; D005462:Fluorine Radioisotopes; D006146:Guanidines; D019275:Radiopharmaceuticals; D016194:Receptors, N-Methyl-D-Aspartate; D013438:Sulfhydryl Compounds; D013440:Sulfides