1016167-58-0Relevant articles and documents
Synthesis, radiofluorination, and in vitro evaluation of pyrazolo[1,5-a]pyridine-based dopamine D4 receptor ligands: Discovery of an inverse agonist radioligand for PET
Prante, Olaf,Tietze, Rainer,Hocke, Carsten,L?ber, Stefan,Hübner, Harald,Kuwert, Torsten,Gmeiner, Peter
, p. 1800 - 1810 (2008)
A series of fluoro-substituted analogs structurally derived from the aminomethyl-substituted pyrazolo[1,5-a]pyridine lead compounds 9 (FAUC 113) and 10 (FAUC 213) were synthesized and evaluated as high-affinity D4 receptor (D4R) ligands (3a-3h, Ki = 1.3-28 nM). The para-fluoroethoxy-substituted derivatives 3f and 3h revealed an outstanding D4 subtype selectivity of more than 3 orders of magnitude over both congeners D2 and D3 combined with inverse agonism at D4R. The corresponding 18F-labeled radioligands revealed high serum stability in vitro and log P values of 2-3. In vitro rat brain autoradiography showed specific binding of [18F]3h in distinct brain regions, including the gyrus dentate of the hippocampus, that were inhibited by both eticlopride (65-80%) and the selective D4R antagonist 10 (78-93%). The observed binding pattern was mainly consistent with the known D4R distribution in the rat brain. Thus, [18F]3h (FAUC F41) represents a potential radioligand for studying the D4R in vivo by positron emission tomography (PET).
