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-fluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.
本发明提供了具有结构 I 的新型α-氟烷基化合物和相应的二氢四苯嗪化合物 IV 以及用于制备此类化合物的中间体。本发明提供的α-氟烷基化合物既有外消旋形式,也有对映体富集形式,可以包含
氟-18 和
氟-19 中的一种或两种。α-氟烷基化合物对 VMAT-2 具有很高的亲和力,VMAT-2 是一种与人类糖尿病等有关的
生物标志物。包含一个
氟-18 基团的 α-氟烷基化合物可用作针对 VMAT-2
生物标志物的 PET 成像剂。非辐射α-氟烷基化合物可用作发现 PET 成像剂的探针。