Hocke Carsten, Prante Olaf, Löber Stefan, Hübner Harald, Gmeiner Peter, Kuwert Torsten
Department of Nuclear Medicine, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
Bioorg Med Chem Lett. 2005 Nov 1;15(21):4819-23. doi: 10.1016/j.bmcl.2005.07.037.
A series of fluoro substituted aryl carboxamides was synthesized revealing high affinity for the dopamine D3 receptor. In contrast to 2-methoxy substitution, a 2,3-dichloro substitution pattern at the phenylpiperazine moiety induces a 10-fold increase of D3 affinity which is expressed by Ki values of 0.53, 1.1, and 9.0 nM for 8b, 8d, and 8f. Applying aromatic 18F-for-Br(Cl) substitution, high radiochemical yields between 76-82% were obtained for [18F]8c-f. The most promising ligand, [18F]8d, was used as imaging agent of the D3 receptor in vitro. However, due to the lack of specific binding, further studies should aim at the development of radioligands with improved D3 receptor selectivity.
合成了一系列氟代芳基羧酰胺，这些化合物对多巴胺D3受体显示出高亲和力。与2-甲氧基取代不同，苯基哌嗪部分的2,3-二氯取代模式使D3亲和力提高了10倍，8b、8d和8f的Ki值分别为0.53、1.1和9.0 nM，体现了这种亲和力。通过芳基18F取代Br(Cl)，[18F]8c-f的放射化学产率很高，在76-82%之间。最有前景的配体[18F]8d在体外用作D3受体的显像剂。然而，由于缺乏特异性结合，进一步的研究应致力于开发具有更高D3受体选择性的放射性配体。
