SYNTHESIS OF CARBON-11-LABELED, FLUORINE-18-LABELED, AND IODINE-125-LABELED GABA(A)-GATED CHLORIDE-ION CHANNEL BLOCKERS - SUBSTITUTED 5-TERT-BUTYL-2-PHENY1-1,3-DITHIANES AND 5-TERT-BUTYL-2-PHENY1-1,3-DITHIANE-OXIDES

A series of substituted 5-tert-butyl-2-phenyl-1,3-dithianes and tert-b utyl-2-phenyl-1,1,3,3-tetraoxo-1,3-dithianes was synthesized as ligand s for the GABA(A) receptor complex-associated neuronal chloride ion ch annels. The in vitro binding affinities of these compounds for the GAB A-gated chloride ion channel were determined by their ability to compe te with [H-3]TBOB for binding to rat brain slices. Of the eight compou nds tested, anophenyl)-2-methyl-1,1,3,3-tetraoxo-1,3-dithiane, 9b, -2- (4-fluorophenyl)-1,1,3,3-tetraoxo-1,3-dithiane, 10, and trans-5-tert-b utyl-2-(4-iodophenyl)-2-methyl-1, 1,3,3-tetraoxo-1,3-dithiane; 11, sho wed moderately high binding affinities (K-i = 41, 180, and 105 nM, res pectively). Four radioligand candidates from this series, tyl-2-(4-cya nophenyl)-2-[C-11]methyl-1,3-dithiane, [C-11]6, -tert-butyl-2-(4-[F-18 ]fluorophenyl)-1,3-dithiane, [F-18]7, 5-tert-butyl-2-(4-[F-18]fluoroph enyl)-1, 1,3,3-tetraoxo-1,3-dithiane, [F-18]10, and odophenyl)-2-methy l-1,1,3,3-tetraoxo-1,3-dithiane, [I-125]11, have been successfully pre pared for evaluation as in vivo imaging agents useful for positron emi ssion tomography and single photon emission computed tomography. Preli minary in vivo studies indicate significant uptake into mouse brain fo r [F-18]7, [F-18]10, and [I-125]11.