In vitro affinities of various halogenated benzamide derivatives as potential radioligands for non-invasive quantification of D2-like dopamine receptors

Benzamide derivatives as radiotracers have played an important role in diagnosing malfunction in dopaminergic neurotransmission. A variety of halogenated and two unsubstituted benzamide derivatives were synthesised and their in vitro affinities to dopaminergic, serotonergic and adrenergic receptors and their lipophilicities were determined. As references IBZM (3), raclopride (4) and FLB457 (5) were tested as well. The two iodinated compounds NAE (27) and NADE (28) displayed Ki values of 0.68 and 14 nM for the D2 receptor. The well-established radiotracers FP (1) and DMFP (2) showed affinities in the same range as did the brominated compounds NABrE (29) and NABrDE (30). The log D7.4 values of 2.91 for NAE (27) and of 2.81 for NADE (28) are in the range of those found for IBZM (3), FP (1) and DMFP (2). These facts allow to expect good properties for the two iodinated compounds NAE (27) and NADE (28) regarding in vivo imaging with SPECT.

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