Thiophenes as phenyl bio-isosteres: application in radiopharmaceutical design--I. Dopamine uptake antagonists.
Possible applications of thiophenes in radiopharmaceutical chemistry have been explored. Thiophene for benzene ring substitution was applied to the synthesis of thienyl-[18F]GBR 13119, an analog of the potent and selective dopamine uptake inhibitor [18F]GBR 13119. In vivo regional brain distribution in mice shows essentially identical results for the thienyl and phenyl compounds (striatum/cerebellum ratios of greater than 4 at 60 min), suggesting successful substitution by the thiophene ring. The extension of this concept to the synthesis of no-carrier-added, high specific activity [18F]fluorothiophenes was examined: 5-[18F]fluoro-2-2-thiophene carboxaldehyde was prepared in 10-20% yields by an unprecedented [18F]fluoride-for-bromo substitution of 5-bromo-2-thiophenecarboxaldehyde. The possible advantages of thiophenes (lower log P, altered metabolism) in radiopharmaceutical chemistry are discussed.
Kilbourn
M R
MR
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; D010879:Piperazines; C062339:thienyl-GBR 13119; D004298:Dopamine