SYNTHESIS OF (N-[C-11]METHYL)Y-29794, A COMPETITIVE INHIBITOR OF PROLYL ENDOPEPTIDASE

Prolyl endopeptidase (PEP: [E.C.3.4.21.26]) is a widely distributed se rine peptidase that cleaves a variety of oligopeptides in the brain an d peripheral tissues. Y-29794 hylaminooctylthio)-6-isopropyl-3-pyridyl -2-thienyl ketone) is a potent competitive reversible inhibitor of thi s enzyme. In order to study the biodistribution of PEP in vivo we have synthesized (N-[C-11]methyl)Y-29794, by [C-11]alkylation of the N-des methyl precursor. The radiotracer was purified by silica gel Sep-Pak a nd was obtained in 10-17% yields (EOB: synthesis times shorter than 45 min) with >98% radiochemical purities and specific activities >550 Ci /mmol (EOS).