Synthesis and biological evaluation of novel fluoro and iodo quinoline carboxamides as potential ligands of NK-3 receptors for in vivo imaging studies.

摘要

In order to develop radioligands of human NK-3 receptor (hNK-3r) for imaging studies by positron emission tomography (PET) or single photon emission computed tomography (SPECT), a new series of fluoro- and iodo-quinoline carboxamides were synthesized and evaluated in a target receptor binding assay. Compared to the unsubstituted parent compound SB 223 412 ( [Formula: see text] nM+/-9), affinity was not altered for the analogues 1c and 2c bearing a fluorine in position 8 ( [Formula: see text] approximately 24-27nM), and was only slightly reduced for compounds 1b, 2b, 1e and 2e fluorinated or iodinated at the position 7 ( [Formula: see text] approximately 49-67nM). A drastic reduction in binding ( [Formula: see text] [Formula: see text] 115nM) was observed for all other halogenated compounds 1a, 2a, 1d, 2d, 1f and 2f.