ALPHA-FLUOROALKYL TETRABENAZINE AND DIHYDROTETRABENAZINE IMAGING AGENTS AND PROBES

摘要

The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV and intermediates useful in the preparation of such compounds. The alpha-fluoroalkyl compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine- 18 and fluorine 19. The alpha-fluoroalkyl compounds are shown to possess high affinity for VMAT-2, a biomarker implicated, for example, in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine- 18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-tluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.