Precursors of glutamate derivatives
This invention relates to novel precursors suitable for 18 F radiolabeling of glutamate derivatives, methods for preparing such compounds and its intermediates, compositions comprising such compounds, kits comprising such compounds or compositions and methods for 18 F radiolabeling of glutamate derivatives wherein the obtained 18 F radiolabeled glutamate derivatives are suitable for diagnostic imaging by Positron Emission Tomography (PET) of proliferative diseases e.g. tumor in mammals.
1. A compound of the formula I
wherein
R 1 is triphenylmethyl,
A is selected from the group consisting of:
a) Monocyclic aryl,
b) Bicyclic aryl,
c) Biaryl,
d) Monocyclic heteroaryl, and
e) Bicyclic heteroaryl
optionally, A is bearing one or more substituents selected from the group consisting of:
a) Halogen,
b) Nitro,
c) Alkyl,
d) Trifluoromethyl, and
e) Z,
wherein Z is
where R 1 is triphenylmethyl, and
# indicates the position of the bond to A, or
a single isomer, tautomer, diastereomer, enantiomer or stereoisomer thereof, or mixtures thereof, or a suitable salt thereof.
2. The compound according to claim 1 wherein
A is selected from the group consisting of:
a) phenyl,
b) biphenyl,
c) naphthyl, and
d) quinolinyl,
optionally, A is bearing one or more substituents selected from the group consisting of:
a) Halogen,
b) Nitro,
c) Ci—C 3 alkyl,
d) Trifluoromethyl, and
e) Z.
3. The compound according to claim 1 with (2S,4S)-configuration of formula 1a
R 1 and A are as defined in claim 1 .
4. Compound according to claim 1 selected from the list below
Di-tert-butyl (4S)-4-(3-{[(4-nitrophenyl)sulfonyl]oxy}propyl)-N-trityl-L-glutamate
Di-tert-butyl (4S)-4-(3-{[(3-nitrophenyl)sulfonyl]oxy}propyl)-N-trityl-L-glutamate
Di-tert-butyl) (4S)-4-{3-[biphenyl-4-ysulfonyl)oxy]propyl}-N-trityl-L-glutamate
Di-tert-butyl (4S)-4-{3-[(2-naphthylsulfonyl)oxy]propyl}-N-trityl-L-glutamate
Di-tert-butyl (4S)-4-{3-[(1-naphthylsulfonyl)oxy]propyl}-N-trityl-L-glutamate
Di-tert-butyl (4S)-4-(3-{[(2,4,6-trichlorophenyl)sulfony]oxy}propyl)-N-trityl-L-glutamate
Tetra-tert-butyl (2S,4S,2′S,4′S)-2,2′-[biphenyl-4,4′-diylbis(sulfonyloxypropane-3,1-diyl)]bis[4-(tritylamino)pentanedioate]
Di-tert-butyl (4S)-4-(3-{[(7-nitro-1-naphthyl)sulfonyl]oxy}propyl)-N-trityl-L-glutamate
Di-tert-butyl (4S)-4-[3-({[4-nitro-3-(trifluoromethyl)phenyl]sulfonyl}oxy)propyl]-N-trityl-L-glutamate
di-tert-butyl (4S)-4-(3-{[(4-methylphenyl)sulfonyl]oxy}propyl)-N-trityl-L-glutamate
di-tert-butyl (4R)-4-{3-[(2-naphthylsulfonyl)oxy]propyl}-N-trityl-L-glutamate
5. A compound of Formula I according to claim 1 in the solid form.
6. A method for obtaining compounds of formula I comprising the step:
Sulfonylation of a compound of Formula II with a sulfonylhalide or sulfonyl anhydride having a suitable substituent A,
wherein R 1 is triphenylmethyl,
A is selected from the group:
a) Monocyclic aryl,
b) Bicyclic aryl,
c) Biaryl,
d) Monocyclic heteroaryl, and
e) Bicyclic heteroaryl
optionally, A is bearing one or more substituents selected from the group comprising:
a) Halogen,
b) Nitro,
c) Alkyl,
d) Trifluoromethyl, and
e) Z,
wherein Z is
R 1 is triphenylmethyl (Trityl), and
# indicates the position of the bond to A.
7. The method according to claim 6 for obtaining a compound with (2S,4S)-configuration (of formula 1a wherein the compound of formula II is a compound of the formula IIa:
8. A composition comprising a compound of formula I.
9. A kit comprising one vial or more than one vial comprising a predetermined quantity of compounds of Formula I.