162760-81-8Relevant articles and documents
Synthesis of ω-Fluoroalkoxy and Alkoxy Derivatives of Raclopride: Evaluation as Radioligands for PET study of Cerebral Dopamine D2 Receptors
Banks, William R.,Moerlein, Stephen M.,Parkinson, David,Welch, Michael J.
, p. 150 - 173 (2007/10/03)
A series of analogues of the dopamine D2 receptor antagonist raclopride were evaluated as radiopharmaceuticals for positron emission tomography (PET). In vitro assays indicate that the D2 affinity of the ligands are descreased by replacement of the 2-methoxy group of raclopride with ω-fluoroalkoxy substituents, and increased by removal of the 6-hydroxy substituent. The 2-fluoroethoxy derivative of deshydroxy raclopride, [(S)-2-[(3,5)-dichloro-2-(2'-fluoroethoxy)benzamido)-methyl]-1-ethylpyrrolidine], exhibited a D2 affinity (Ki = 12nM) close to that of raclopride itself (Ki = 9.5 nM). A one-step radiosynthesis of the fluorine-18 labeled analogue of this ligand with specific radioactivity > 2 Ci/μmol and 35 percent radiochemical yield (decay-corrected) was developed; there was poor receptor-specific localization of this radioligand in vivo in rats, however. These results underscore the inadequacy of in vitro receptor assays as the sole screening test for PET radiopharmaceuticals. Future development of this series of ligands should emphasize placement of the fluorine-18 label at an aromatic site remote from the intramolecular hydrogen-bonding sites necessary for receptor-active conformations
