Fluoro analogs of WAY-100635 with varying pharmacokinetics properties

Radiolabeled derivatives of WAY-100635 have been shown to be important for imaging in vivo because of their antagonist properties and their specificit y for the 5-hydroxytryptamine(1A) (5-HT1A) receptor. Our goal is to prepare a series of radiofluorinated derivatives of WAY-100635 that, in the rat, r ange in pharmacokinetic properties from nearly irreversible to reversible i n their behavior. It appears that derivatives containing a cyclohexanecarbo xylic acid (e.g., FCWAY) with its high affinity and high target to nontarge t contrast, has properties suited to measure receptor concentration. Deriva tives based on phenylcarboxamide (e.g., FBWAY and MeFBAWAY) have properties more suited to the measurement of changes in endogenous serotonin. The com pound containing the pyrimidine moiety in place of the pyridine moeity in F BWAY (FBWAY 1,3N) appears to have intermediate properties. NUCL MED BIOL 27 ;5:457-462, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.