Synthesis and in vitro evaluation of (18)F-labelled S-fluoroalkyl diarylguanidines: Novel high-affinity NMDA receptor antagonists for imaging with PET

Edward G Robins; Yongjun Zhao; Imtiaz Khan; Anthony Wilson; Sajinder K Luthra; Erik Rstad

doi:10.1016/j.bmcl.2010.01.052

Synthesis and in vitro evaluation of (18)F-labelled S-fluoroalkyl diarylguanidines: Novel high-affinity NMDA receptor antagonists for imaging with PET

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1749-51. doi: 10.1016/j.bmcl.2010.01.052. Epub 2010 Jan 20.

Authors

Edward G Robins¹, Yongjun Zhao, Imtiaz Khan, Anthony Wilson, Sajinder K Luthra, Erik Rstad

Affiliation

¹ GE Healthcare MDx Research, MRC Cyclotron Building, Hammersmith Hospital, London W12 0NN, United Kingdom.

PMID: 20138515
DOI: 10.1016/j.bmcl.2010.01.052

Abstract

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.

MeSH terms

Animals
Binding Sites
Fluorine Radioisotopes
Guanidines / chemical synthesis*
Guanidines / chemistry
Guanidines / pharmacology
Positron-Emission Tomography
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / chemistry
Rats
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism
Sulfhydryl Compounds / pharmacology
Sulfides / chemical synthesis*
Sulfides / chemistry

Substances

CNS 5161
Fluorine Radioisotopes
Guanidines
Radiopharmaceuticals
Receptors, N-Methyl-D-Aspartate
Sulfhydryl Compounds
Sulfides