Johannsen B, Scheunemann M, Spies H, Brust P, Wober J, Syhre R, Pietzsch H J
Forschungszentrum Rossendorf E.V., Institut Für Bioanorganische und Radiopharmazeutische Chemie, Dresden, Germany.
Nucl Med Biol. 1996 May;23(4):429-38. doi: 10.1016/0969-8051(96)00015-7.
Starting from the lead structure of ketanserin, a prototypic serotonin (5-HT) antagonist, new oxotechnetium(V) and oxorhenium(V) complexes were synthesized that are able to compete with [3H]ketan-serin in receptor-binding assays. To imitate organic 5-HT2 receptor ligands, fragments of ketanserin were combined with chelate moieties. Neutral compounds of the general formula [MOL1L2] (M = Tc, Re; L1 = HS-CH2CH2-S-CH2CH2-SH, N-(2-mercaptophenyl)salicylideneimine, N-(2-mercaptoethyl)-salicylideneimine, 3-(2-([N,N-bis(2-mercapto-S-ethyl)]-amino)ethyl)-2,4-(1H, 3H)-quinazolinedione and L2 = HS-R with R = subst. alkyl) were prepared by common action of a Tc(V) or Re(V) precursor with a mixture of equimolar amounts of a tridentate ligand L1 and a monodentate thiolate L2 bearing fragments of the lead structure. Lipophilic complexes consisting of a small S4 thiolate/thioether chelate unit, protonable nitrogen-containing spacer, and simple benzyl moiety significantly inhibited the specific binding of [3H]ketan-serin with IC50 values between 10 and 50 nM.
从原型5-羟色胺（5-HT）拮抗剂酮色林的先导结构出发，合成了新的锝（V）和铼（V）氧配合物，它们在受体结合试验中能够与[3H]酮色林竞争。为了模拟有机5-HT2受体配体，将酮色林的片段与螯合部分结合。通过使锝（V）或铼（V）前体与等摩尔量的三齿配体L1和带有先导结构片段的单齿硫醇盐L2的混合物共同作用，制备了通式为[MOL1L2]（M = Tc，Re；L1 = HS-CH2CH2-S-CH2CH2-SH，N-（2-巯基苯基）水杨基亚胺，N-（2-巯基乙基）水杨基亚胺，3-（2-（[N，N-双（2-巯基-S-乙基）]氨基）乙基）-2,4-（1H，3H）-喹唑啉二酮，L2 = HS-R，R = 取代烷基）的中性化合物。由小的S4硫醇盐/硫醚螯合单元、可质子化的含氮间隔基和简单苄基部分组成的亲脂性配合物以10至50 nM之间的IC50值显著抑制了[3H]酮色林的特异性结合。
