科研之友
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摘要
Synthesis, biological activity, and structure-selectivity relationship (SSR) studies of a novel series of potential dopamine D3 receptor radioligands as imaging agents for positron emission tomography (PET) are reported. Considering a structurally diverse library of D3 ligands, SSR studies were performed for a new series of fluorinated pyridinylphenyl amides using CoMFA and CoMSIA methods. The in vitro D3 affinities of the predicted series of biphenyl amide ligands 9a-d revealed single-digit to sub-nanomolar potencies (K-i=0.52-1.6 nM), displaying excellent D3 selectivity over the D2 subtype of 110- to 210-fold for the test compounds 9 a-c. Radiofluorination by nucleophilic substitution of Br or NO2 by F-18 led to radiochemical yields of 66-92 % for [F-18]9a-d. However, the specific activities of [F-18]9b and [F-18]9d were insufficient, rendering their use for in vivo studies impossible. Biodistribution studies of [F-18]9 a and [F-18]9c using rat brain autoradiography revealed accumulation in the ventricles, thus indicating insufficient biokinetic properties of [F-18]9a and [F-18]9c for D3 receptor imaging in vivo.
- 出版日期2010-6
