SPECT imaging agents for serotonin transporters

摘要

The present invention is directed to compounds of Formula (I) or pharmaceutically acceptable salts thereof; wherein X is hydrogen, Cl, Br, I, NO₂, NR³R⁴ or —L—Ch; Y is hydrogen, —CH₂OR⁵, —CH₂NCH₃R¹, NO₂, NR³R⁴ or —L—Ch; Y′ is hydrogen, —CH₂OH⁵, —CH₂NCH₃R¹, NO₂, NR³R⁴ OR —L—Ch; provided that at least one of the Y or Y′ is —CH₂NCH₃R¹; Z is S, O, NR⁶ CR⁷R⁸, C(O) or —C(═CR⁷R⁸)-; A is hydrogen, Cl, I, Br or —L—Ch; R¹ is hydrogen, C₁-C₅ alkyl, C₃-C₈ cycloalkyl C_1-5 alkylcarbonyl, (C₃-C₈ cycloalkyl) carbonyl, pnenyl, benzyl, naphthyl, naphthylmethyl or L—Ch; R² is hydrogen or methyl; and R³-R⁸ are as defined herein. Radiolabeled compounds of the invention are useful as selective serotonin transporter (SERT) imaging agents for single photon emission tomography (SPECT). As such the compounds are useful for studying the underlying pharmacology and interaction of specific serotinin reuptake site inhibitors (SSRI), commonly used antidepressants, at the SERT sites in the human brain. Certain compounds of the invention, including IDAM (5-iodo-2[[2-2-[(dimethylamino)methyl]phenyl]thio]benzylalcohol) display affinity to SERT sites and show more high selectively for SERT over NET and DAT.