3-Amino-4-(2-((4-[18F]fluorobenzyl)methylamino)methylphenylsulfanyl)benzonitrile, an F-18 fluorobenzyl analogue of DASB: synthesis, in vitro binding, and in vivo biodistribution studies.
3-amino-4-(2[11C]methylaminomethylphenylsulfanyl)benzonitrile (C-11 DASB) exhibits excellent in vitro and in vivo properties toward the serotonin transporter. If labeled with a longer physical half-life radioisotope, this ligand could be more attractive to research groups lacking an on-site cyclotron or lacking C-11 synthesis capabilities. We produce p-[18F]fluorobenzyl iodide on a routine basis to synthesize several neuroimaging agents. Therefore, it was straightforward for us to substitute the DASB precursor with this prosthetic group and assess its biological properties. We designed a different synthesis strategy to obtain the DASB precursor (desmethyl DASB). Herein we report an efficient and facile synthetic route that provides higher chemical yields of 3-amino-4-(2-aminomethylphenylsulfanyl)benzonitrile and related analogues. In addition, we report our results from incorporating p-[18F]fluorobenzyl iodide in DASB precursor and its affect on the in vitro and in vivo biological properties of the DASB.
Garg
Sudha
S
PET Center, Department of Radiological Sciences, Wake Forest University Medical Center, Winston Salem, North Carolina 27157, USA.
Thopate
Shankar R
SR
Minton
Richard C
RC
Black
Kimberly W
KW
Lynch
Andrew J H
AJ
Garg
Pradeep K
PK
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D001596:Benzylamines / Q000737:chemistry*; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes / Q000138:chemical synthesis* / Q000737:chemistry; D006207:Half-Life; D008024:Ligands; D051379:Mice; D008956:Models, Chemical; D009943:Organophosphorus Compounds / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000494:pharmacology; D013440:Sulfides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D001596:Benzylamines; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D008024:Ligands; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; C083672:4-fluorobenzyl iodide