[18F] labelled L-glutamic acid, [18F] labelled glutamine, their derivatives, their use and processes for their preparation

摘要

Fluorine-18 labeled derivatives (I) and (II) of glutamic acid, glutamine and related aminopentanedioic acid compounds, substituted by fluorine-18 or a fluorine-18-containing group in the 3- or 4-position, are new. Fluorine-18 labeled glutamic acid and glutamine compounds of formulae (I) and (II) (including their enantiomers and diastereomers) are new. A : OH, alkoxy, hydroxyalkoxy, -O-alkyl-(O-(1-4C) alkyl) n-O-(1-4C) alkyl, dialkylamino, NH 2, NHL, OL or OZ; G, G' : OH, OZ, alkoxy, alkenyloxy, -O-alkyl-(O-(1-4C) alkyl) n-O-(1-4C) alkyl or alkynyloxy; R 1>, R 2> : H, 18-F, (18-F)-fluoroalkoxy, (18-F)-fluoroalkyl, (18-F)-fluorohydroxyalkyl, (18-F)-fluoroalkenyl, (18-F)-fluoroalkynyl, OH, alkyl or alkoxy; provided that one of R 1> and R 2> contains a single 18-F isotope and the other is free of 18-F isotope; L, L' : alkyl, alkenyl, -alkyl-(O-(1-4C) alkyl) n-O-(1-4C) alkyl or alkynyl; Z : 1 equivalent of metal cation; n : 0-3; A' : OH, alkoxy, hydroxyalkoxy, -O-alkyl-(O-(1-4C) alkyl) n-O-(1-4C) alkyl, dialkylamino, NH 2, NHU, NHL' or OL'; Q : NHCOOM, 1,1-dimethylpropynylamino, NHCOM', tritylamino, p-methoxytritylamino, di-(p-methoxy)-tritylamino, -N=CX'X'' or N(COOtBu) 2; M : tBu, allyl, benzyl, Et, Me, propyl, CH 2CCl 3, C(Me) 2Ph or C(Me) 2-pC 6H 4-Ph; M' : cyclobutyl, 1-methylcyclobutyl, vinyl, allyl, adamantyl, CHPh 2, cinnamyl, H or Ph; U : COOtBu, COOCH 2CH=CH 2, COOCH 2Ph, COOMe, COOEt or COO-propyl; X, X' : alkyl, optionally substituted or aralkyl; unless specified otherwise alkyl moieties have 1-5C and alkenyl or alkynyl moieties 2-5C. Independent claims are included for: (1) the preparation of (I) and (II); (2) new glutamic acid or glutamine derivative intermediates of formula (III) (including their enantiomers and diastereomers); and (3) the use of glutamic acid or glutamine derivatives of formula (IV) and pyrrolidone derivatives of formula (V) (including their enantiomers and diastereomers) for the preparation of (I) or (II). A'', A''' : as for A', except that in NHU U is not COOMe or COO-propyl and that n= 0-2 in (III) and (IV); G'', G''' : as for G; Q', Q'' : as for Q; R 3>, R 4> : H, (E)-alkoxy, (E)-alkyl, (E)-hydroxyalkyl, (E)-alkenyl, (E)-alkynyl, OH, alkyl or alkoxy; provided that one of R 3> and R 4> contains E and the other is free of E; E, E' : Cl, Br, mesyloxy, trifluoromesyloxy, nonafluorobutoxy or tosyloxy; one of R 5>, R 5> : H and the other= E'; Q''' : H, COOM or COM'; unless specified otherwise alkyl moieties have 1-5C and alkenyl or alkynyl moieties 2-5C. [Image] [Image].