Novel [F-18]-labelled L-glutamic acid and L-glutamine derivatives (II), their use and processes for their preparation
What is described are the compounds and the synthesis of [F-18]-labelled L-glutamic acid, [F-18]-labelled L-glutamate, their derivatives of the formula (I) and their use.
1 ) Compounds of the general formula I
in which
A represents
a) hydroxyl,
b) branched or straight-chain C 1 -C 5 alkoxy,
c) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
e) N(C 1 -C 5 alkyl) 2 ,
f) NH 2 ,
g) N(H)-L,
h) O-L or
i) O—Z,
G represents
a) hydroxyl,
b) O—Z,
c) branched or straight-chain O—C 1 -C 5 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkenyl,
e) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) a -O—C 1 -C 4 alkyl,
f) branched or straight-chain O—C 2 -C 5 alkynyl or
g) triphenylmethoxy,
R 1 and R 2 represent
a) hydrogen,
b) branched or straight-chain 18 F—C 6 -C 10 alkoxy,
c) branched or straight-chain 18 F—C 6 -C 10 alkyl,
d) branched or straight-chain 18 F—C 6 -C 10 alkenyl,
e) branched or straight-chain 18 F—C 6 -C 10 alkynyl,
f) hydroxyl,
g) branched or straight-chain C 1 -C 5 alkyl or
h) branched or straight-chain C 1 -C 5 alkoxy,
with the proviso that one of the substituents R 1 or R 2 contains exactly one 18 F isotope and the respective other substituent contains no 18 F isotope,
L represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 1 -C 5 alkynyl, and
Z represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
2 ) Compounds according to claim 1 , selected from the group of compounds of the formulae:
3 ) Process for preparing compounds of the general formula (I) according to claim 1 ,
which comprises
removing one or more protective groups present in a compound of the formula (II)
in which
A′ represents
a) hydroxyl,
b) branched or straight-chain C 1 -C 5 alkoxy
c) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl-O—C 1 -C 4 alkyl,
e) N(C 1 -C 5 alkyl) 2 ,
f) NH 2 ,
g) N(H)-L′,
h) O-L′,
G′ represents
a) hydroxyl,
b) O—Z′,
c) branched or straight-chain O—C 1 -C 5 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkenyl,
e) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
f) branched or straight-chain O—C 2 -C 5 alkynyl or
g) triphenylmethoxy,
R 1 and R 2 represent
a) hydrogen,
b) branched or straight-chain 18 F—C 6 -C 10 alkoxy,
c) branched or straight-chain 18 F—C 6 -C 10 alkyl,
d) branched or straight-chain 18 F—C 6 -C 10 alkenyl,
e) branched or straight-chain 18 F—C 6 -C 10 alkynyl,
f) hydroxyl,
g) branched or straight-chain C 1 -C 5 alkyl or
h) branched or straight-chain C 1 -C 5 alkoxy,
with the proviso that exactly one of the substituents R 1 or R 2 contains exactly one 18 F isotope and the respective other substituent contains no 18 F isotope,
Q represents
a) N(H)-tert-butoxycarbonyl,
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
e) N(H)-2,2,2-trichloroethoxycarbonyl,
f) N(H)-1,1-dimethylpropynyl,
g) N(H)-1-methyl-1-phenylethoxycarbonyl,
h) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
i) N(H)-cyclobutylcarbonyl,
j) N(H)-1-methylcyclobutylcarbonyl,
k) N(H)-vinylcarbonyl,
l) N(H)-allylcarbonyl,
m) N(H)-adamantylcarbonyl,
n) N(H)-diphenylmethylcarbonyl,
o) N(H)-cinnamylcarbonyl,
p) N(H)-formyl,
q) N(H)-benzoyl,
r) N(H)-trityl,
s) N(H)-n-methoxydiphenylmethyl,
t) N(H)-di(p-methoxyphenyl)phenylmethyl,
u)
v) N-(tert-butoxycarbonyl) 2 ,
L′ represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight chain C 1 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X′ and X″ independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted aralkyl or
d) substituted or unsubstituted heteroaryl,
Z′ represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
4 ) Compounds of the general formula (II):
in which
A′ represents
a) hydroxyl,
b) branched or straight-chain C 1 -C 5 alkoxy,
c) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
e) N(C 1 -C 5 alkyl) 2 ,
f) NH 2 ,
g) N(H)-L′,
h) O-L′,
G′ represents
a) hydroxyl,
b) O—Z′,
c) branched or straight-chain O—C 1 -C 5 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkenyl,
e) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
f) branched or straight-chain O—C 2 -C 5 alkynyl or
g) triphenylmethoxy,
R 1 and R 2 represent
a) hydrogen,
b) branched or straight-chain 18 F—C 6 -C 10 alkoxy,
c) branched or straight-chain 18 F—C 6 -C 10 alkyl,
d) branched or straight-chain 18 F—C 6 -C 10 alkenyl,
e) branched or straight-chain 18 F—C 6 -C 10 alkynyl,
f) hydroxyl,
g) branched or straight-chain C 1 -C 5 alkyl or
h) branched or straight-chain C 1 -C 5 alkoxy,
with the proviso that exactly one of the substituents R 1 or R 2 contains exactly one 18 F isotope and the respective other substituent contains no 18 F isotope,
Q represents
a) N(H)-tert-butoxycarbonyl,
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
e) N(H)-2,2,2-trichloroethoxycarbonyl,
f) N(H)-1,1-dimethylpropynyl,
g) N(H)-1-methyl-1-phenylethoxycarbonyl,
h) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
i) N(H)-cyclobutylcarbonyl,
j) N(H)-1-methylcyclobutylcarbonyl,
k) N(H)-vinylcarbonyl,
l) N(H)-allylcarbonyl,
m) N(H)-adamantylcarbonyl,
n) N(H)-diphenylmethylcarbonyl,
o) N(H)-cinnamylcarbonyl,
p) N(H)-formyl,
q) N(H)-benzoyl,
r) N(H)-trityl,
s) N(H)-p-methoxydiphenylmethyl,
t) N(H)-di(p-methoxyphenyl)phenylmethyl,
u)
v) N-(tert-butoxycarbonyl) 2 ,
L′ represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 1 -C 5 alkynyl,
X′ and X″ independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted aralkyl or
d) substituted or unsubstituted heteroaryl,
Z′ represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
5 ) Compounds according to claim 4 , selected from the group of compounds of the formulae:
6 ) Process for preparing compounds of the general formula (II) according to claim 4 ,
which comprises
reacting a compound of the formula (III) with F-18 fluoride,
in which
A″ represents
a) branched or straight-chain C 1 -C 5 alkoxy,
b) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) N(C 1 -C 5 alkyl) 2 ,
e) NH 2 ,
f) N(H)-L″,
g) O-L″,
G″ represents
a) branched or straight-chain O—C 1 -C 5 alkyl,
b) branched or straight-chain O—C 2 -C 5 alkenyl,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkynyl or
e) triphenylmethoxy,
R 3 and R 4 represent
a) hydrogen,
b) branched or straight-chain E-C 6 -C 10 alkoxy,
c) branched or straight-chain E-C 6 -C 10 alkyl,
d) branched or straight-chain E-C 6 -C 10 alkenyl,
e) branched or straight-chain E-C 6 -C 10 alkenyl,
f) hydroxyl,
g) branched or straight-chain C 1 -C 5 alkyl or
h) branched or straight-chain C 1 -C 5 alkoxy,
with the proviso that exactly one of the substituents R 3 or R 4 contains an E and the respective other substituent contains no E,
E represents a leaving group,
Q′ represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
g) N(H)-2,2,2-trichloroethoxycarbonyl,
h) N(H)-1,1-dimethylpropynyl,
i) N(H)-1-methyl-1-phenylethoxycarbonyl,
j) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N(H)-cyclobutylcarbonyl,
l) N(H)-1-methylcyclobutylcarbonyl,
m) N(H)-vinylcarbonyl,
n) N(H)-allylcarbonyl,
o) N(H)-adamantylcarbonyl,
p) N(H)-diphenylmethylcarbonyl,
q) N(H)-cinnamylcarbonyl,
r) N(H)-formyl,
s) N(H)-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxydiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
L″ represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X′ and X″ independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
7 ) Compounds of the formula (III)
in which
A″ represents
a) branched or straight-chain C 1 -C 5 alkoxy,
b) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) N(C 1 -C 5 alkyl) 2 ,
e) NH 2 ,
f) N(H)-L″,
g) O-L″,
G″ represents
a) branched or straight-chain O—C 1 -C 5 alkyl,
b) branched or straight-chain O—C 2 -C 5 alkenyl,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkynyl or
e) triphenylmethoxy,
R 3 and R 4 represent
a) hydrogen,
b) branched or straight-chain E-C 6 -C 10 alkoxy,
c) branched or straight-chain E-C 6 -C 10 alkyl,
d) branched or straight-chain E-C 6 -C 10 alkenyl,
e) branched or straight-chain E-C 6 -C 10 alkynyl,
f) hydroxyl,
g) branched or straight-chain C 1 -C 5 alkyl or
h) branched or straight-chain C 1 -C 5 alkoxy,
with the proviso that exactly one of the substituents R 3 or R 4 contains an E and the respective other substituent contains no E,
E represents a leaving group,
Q′ represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
g) N(H)-2,2,2-trichloroethoxycarbonyl,
h) N(H)-1,1-dimethylpropynyl,
i) N(H)-1-methyl-1-phenylethoxycarbonyl,
j) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N(H)-cyclobutylcarbonyl,
l) N(H)-1-methylcyclobutylcarbonyl,
m) N(H)-vinylcarbonyl,
n) N(H)-allylcarbonyl,
o) N(H)-adamantylcarbonyl,
p) N(H)-diphenylmethylcarbonyl,
q) N(H)-cinnamylcarbonyl,
r) N(H)-formyl,
s) N(H)-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxydiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
L″ represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X′ and X″ independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
8 ) A method comprising using the compounds of the formula (III) for preparing compounds of the formula (I) or (II):
in which
A″ represents
a) branched or straight-chain C 1 -C 5 alkoxy,
b) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) N(C 1 -C 5 alkyl) 2 ,
e) NH 2 ,
f) N(H)-L″,
g) O-L″,
G″ represents
a) branched or straight-chain O—C 1 -C 5 alkyl,
b) branched or straight-chain O—C 2 -C 5 alkenyl,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkynyl or
e) triphenylmethoxy,
R 3 and R 4 represent
a) hydrogen,
b) branched or straight-chain E-C 6 -C 10 alkoxy,
c) branched or straight-chain E-C 6 -C 10 alkyl,
d) branched or straight-chain E-C 6 -C 10 alkenyl,
e) branched or straight-chain E-C 6 -C 10 alkynyl,
f) hydroxyl,
g) branched or straight-chain C 1 -C 5 alkyl or
h) branched or straight-chain C 1 -C 5 alkoxy,
with the proviso that exactly one of the substituents R 3 or R 4 contains an E and the respective other substituent contains no E,
E represents a leaving group,
Q′ represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
g) N(H)-2,2,2-trichloroethoxycarbonyl,
h) N(H)-1,1-dimethylpropynyl,
i) N(H)-1-methyl-1-phenylethoxycarbonyl,
j) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N(H)-cyclobutylcarbonyl,
l) N(H)-1-methylcyclobutylcarbonyl,
m) N(H)-vinylcarbonyl,
n) N(H)-allylcarbonyl,
o) N(H)-adamantylcarbonyl,
p) N(H)-diphenylmethylcarbonyl,
q) N(H)-cinnamylcarbonyl,
r) N(H)-formyl,
s) N(H)-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
L″ represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X′ and X″ independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
9 ) Compounds of the formula (IV)
in which
G′″ represents
a) branched or straight-chain O—C 1 -C 5 alkyl,
b) branched or straight-chain O—C 2 -C 5 alkenyl,
c) branched or straight-chain O—C 1 -C 5 alkyl) n -O—C 1 -C 4 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkynyl or
e) triphenylmethoxy,
R 5 and R 6 represent
a) hydrogen,
b) hydroxyl,
c) branched or straight-chain C 1 -C 5 alkyl,
d) branched or straight-chain C 1 -C 5 alkoxy or
e) R 7 -E′,
with the proviso that exactly one of the substituents R 5 or R 6 contains an E′ and the respective other substituent contains no E′,
E′ represents a leaving group
R 7 represents
a) branched or straight-chain C 6 -C 10 alkoxy,
b) branched or straight-chain C 6 -C 10 alkyl,
c) branched or straight-chain C 6 -C 10 alkenyl or
d) branched or straight-chain C 6 -C 10 alkynyl,
Q′″ represents
a) N-tert-butoxycarbonyl
b) N-allyloxycarbonyl,
c) N-benzyloxycarbonyl,
d) N-ethoxycarbonyl,
e) N-methoxycarbonyl,
f) N-propoxycarbonyl,
g) N-2,2,2-trichloroethoxycarbonyl,
h) hydrogen,
i) N-1-methyl-1-phenylethoxycarbonyl,
j) N-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N-cyclobutylcarbonyl,
l) N-1-methylcyclobutylcarbonyl,
m) N-vinylcarbonyl,
n) N-allylcarbonyl,
o) N-adamantylcarbonyl,
p) N-diphenylmethylcarbonyl,
q) N-cinnamylcarbonyl,
r) N-formyl,
s) N-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
X′″ and X″″ independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
10 ) A method comprising using compounds of the formula (VI) for preparing compounds of the formula (I) or (II):
in which
G′″ represents
a) branched or straight-chain O—C 1 -C 5 alkyl,
b) branched or straight-chain O—C 2 -C 5 alkenyl,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkynyl or
e) triphenylmethoxy,
R 5 and R 6 represent
a) hydrogen,
b) hydroxyl,
c) branched or straight-chain C 1 -C 5 alkyl,
d) branched or straight-chain C 1 -C 5 alkoxy or
e) R 7 -E′,
with the proviso that exactly one of the substituents R 5 or R 6 contains an E′ and the respective other substituent contains no E′,
E′ represents a leaving group
R 7 represents
a) branched or straight-chain C 6 -C 10 alkoxy,
b) branched or straight-chain C 6 -C 10 alkyl,
c) branched or straight-chain C 6 -C 10 alkenyl or
d) branched or straight-chain C 6 -C 10 alkynyl,
Q′″ represents
a) N-tert-butoxycarbonyl
b) N-allyloxycarbonyl,
c) N-benzyloxycarbonyl,
d) N-ethoxycarbonyl,
e) N-methoxycarbonyl,
f) N-propoxycarbonyl,
g) N-2,2,2-trichloroethoxycarbonyl,
h) hydrogen,
i) N-1-methyl-1-phenylethoxycarbonyl,
j) N-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N-cyclobutylcarbonyl,
l) N-1-methylcyclobutylcarbonyl,
m) N-vinylcarbonyl,
n) N-allylcarbonyl,
o) N-adamantylcarbonyl,
p) N-diphenylmethylcarbonyl,
q) N-cinnamylcarbonyl,
r) N-formyl,
s) N-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
X′ and X″″ independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
11 ) Imaging kit, comprising compounds of the general formula III or IV.
12 ) Pharmaceutical composition, comprising compounds of the general formula I, II, III or IV and suitable pharmaceutical carrier substances.
13 ) Compounds of the general formula V
in which
A 1 represents
a) hydroxyl,
b) branched or straight-chain C 1 -C 5 alkoxy,
c) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
ed) N(C 1 -C 5 alkyl) 2 ,
f) NH 2 ,
g) N(H)-L 1 ,
h) O-L 1 or
i) O—Z 1 ,
G 1 represents
a) hydroxyl,
b) O—Z 1 ,
c) branched or straight-chain O—C 1 -C 5 alkyl,
d) branched or straight-chain O—C 1 -C 5 alkenyl,
e) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
f) branched or straight-chain O—C 1 -C 5 alkynyl or
g) triphenylmethoxy,
R 8 and R 9 represent
a) hydrogen,
b) substituted or unsubstituted 18 F—C 6 -C 10 mono- or bicyclic aryl,
c) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
d) substituted or unsubstituted 18 F—C 5 -C 10 mono- or bicyclic heteroaryl,
e) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F,
f) substituted or unsubstituted 18 F—C 3 -C 6 cycloalkyl,
g) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl- 18 F,
h) hydroxyl,
i) branched or straight-chain C 1 -C 5 alkyl,
j) branched or straight-chain C 1 -C 5 alkoxy,
k) substituted or unsubstituted O-alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
l) substituted or unsubstituted O-alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F or
m) substituted or unsubstituted O—C 3 -C 6 cycloalkyl- 18 F,
alkylene being optionally interrupted by one or more O, S or N,
with the proviso that one of the substituents R 8 or R 9 contains exactly one 18 F isotope and the respective other substituent contains no 18 F isotope,
L 1 represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
Z 1 represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
14 ) Compounds according to claim 13 , selected from the group of compounds of the formulae:
15 ) Process for preparing compounds of the general formula (V) according to claim 13 ,
which comprises
removing one or more protective groups present in a compound of the formula (VI)
in which
A 2 represents
a) hydroxyl,
b) branched or straight-chain C 1 -C 5 alkoxy,
c) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
e) N(C 1 -C 5 alkyl) 2 ,
f) NH 2 ,
g) N(H)-L 2 or
h) O-L 2
G 2 represents
a) hydroxyl,
b) O—Z 2 ,
c) branched or straight-chain O—C 1 -C 5 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkenyl,
e) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
f) branched or straight-chain O—C 2 -C 5 alkynyl or
g) triphenylmethoxy,
R 8 and R 9 represent
a) hydrogen,
b) substituted or unsubstituted 18 F—C 6 -C 10 mono- or bicyclic aryl,
c) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
d) substituted or unsubstituted 18 F—C 5 -C 10 mono- or bicyclic heteroaryl,
e) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F,
f) substituted or unsubstituted 18 F—C 3 -C 6 cycloalkyl,
g) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl- 18 F
h) hydroxyl,
i) branched or straight-chain C 1 -C 5 alkyl,
j) branched or straight-chain C 1 -C 5 alkoxy,
k) substituted or unsubstituted O-alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
l) substituted or unsubstituted O-alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F or
m) substituted or unsubstituted O—C 3 -C 6 cycloalkyl- 18 F,
alkylene being optionally interrupted by one or more O, S or N,
with the proviso that one of the substituents R 8 or R 9 contains exactly one 18 F isotope and the respective other substituent contains no 18 F isotope,
Q 1 represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
e) N(H)-2,2,2-trichloroethoxycarbonyl,
f) N(H)-1,1-dimethylpropynyl,
g) N(H)-1-methyl-1-phenylethoxycarbonyl,
h) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
i) N(H)-cyclobutylcarbonyl,
j) N(H)-1-methylcyclobutylcarbonyl,
k) N(H)-vinylcarbonyl,
l) N(H)-allylcarbonyl,
m) N(H)-adamantylcarbonyl,
n) N(H)-diphenylmethylcarbonyl,
o) N(H)-cinnamylcarbonyl,
p) N(H)-formyl,
q) N(H)-benzoyl,
r) N(H)-trityl,
s) N(H)-p-methoxyphenyldiphenylmethyl,
t) N(H)-di(p-methoxyphenyl)phenylmethyl,
u)
v) N-(tert-butoxycarbonyl) 2 ,
L 2 represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) or straight-chain C 2 -C 5 alkynyl,
X 1 and X independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted arylalkyl or
d) substituted or unsubstituted heteroaryl,
Z 2 represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
16 ) Compounds of the general formula (VI):
in which
A 2 represents
a) hydroxyl,
b) branched or straight-chain C 1 -C 5 alkoxy,
c) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
e) N(C 1 -C 5 alkyl) 2 ,
f) NH 2 ,
g) N(H)-L 2 or
h) O-L 2
G 2 represents
a) hydroxyl,
b) O—Z 2 ,
c) branched or straight-chain O—C 1 -C 5 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkenyl,
e) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
f) branched or straight-chain O—C 2 -C 5 alkynyl or
g) triphenylmethoxy,
R 8 and R 9 represent
a) hydrogen,
b) substituted or unsubstituted 18 F—C 6 -C 10 mono- or bicyclic aryl,
c) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
d) substituted or unsubstituted 18 F—C 5 -C 10 mono- or bicyclic heteroaryl,
e) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F,
f) substituted or unsubstituted 18 F—C 3 -C 6 cycloalkyl,
g) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl- 18 F,
h) hydroxyl,
i) branched or straight-chain C 1 -C 5 alkyl,
j) branched or straight-chain C 1 -C 5 alkoxy,
k) substituted or unsubstituted O-alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
l) substituted or unsubstituted O-alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F or
m) substituted or unsubstituted O—C 3 -C 6 cycloalkyl- 18 F,
alkylene being optionally interrupted by one or more O, S or N,
with the proviso that one of the substituents R 8 or R 9 contains exactly one 18 F isotope and the respective other substituent contains no 18 F isotope,
Q 1 represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
e) N(H)-2,2,2-trichloroethoxycarbonyl,
f) N(H)-1,1-dimethylpropynyl,
g) N(H)-1-methyl-1-phenylethoxycarbonyl,
h) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
i) N(H)-cyclobutylcarbonyl,
j) N(H)-1-methylcyclobutylcarbonyl,
k) N(H)-vinylcarbonyl,
l) N(H)-allylcarbonyl,
m) N(H)-adamantylcarbonyl,
n) N(H)-diphenylmethylcarbonyl,
o) N(H)-cinnamylcarbonyl,
p) N(H)-formyl,
q) N(H)-benzoyl,
r) N(H)-trityl,
s) N(H)-p-methoxyphenyldiphenylmethyl,
t) N(H)-di(p-methoxyphenyl)phenylmethyl,
u)
v) N-(tert-butoxycarbonyl) 2 ,
L 2 represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X 1 and X 2 independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted arylalkyl or
d) substituted or unsubstituted heteroaryl,
Z 2 represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
17 ) Process for preparing compounds of the general formula (VI) according to claim 16 ,
which comprises
reacting a compound of the formula (VII) with F-18 fluoride
in which
A represents
a) branched or straight-chain C 1 -C 5 alkoxy,
b) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) N(C 1 -C 5 alkyl) 2 ,
e) NH 2
f) N(H)-L 3 or
g) O-L 3 ,
G 3 represents
a) O—Z 3 ,
b) branched or straight-chain O—C 1 -C 5 alkyl,
c) branched or straight-chain O—C 2 -C 5 alkenyl,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
e) branched or straight-chain O—C 1 -C 5 alkynyl or
f) triphenylmethoxy,
R 10 and R 11 represent
a) hydrogen,
b) substituted or unsubstituted E 1 -C 6 -C 10 mono- or bicyclic aryl,
c) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic aryl-E 1 ,
d) substituted or unsubstituted E 1 -C 5 -C 10 mono- or bicyclic heteroaryl,
e) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl-E 1 ,
f) substituted or unsubstituted E 1 -C 3 -C 6 cycloalkyl,
g) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl-E 1 ,
h) hydroxyl,
i) branched or straight-chain C 1 -C 5 alkyl,
j) branched or straight-chain C 1 -C 5 alkoxy,
k) substituted or unsubstituted O-alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
l) substituted or unsubstituted O-alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F or
m) substituted or unsubstituted O—C 3 -C 6 cycloalkyl- 18 F,
alkylene being optionally interrupted by one or more O, S or N,
with the proviso that exactly one of the substituents R 10 or R 11 contains an E 1 and the respective other substituent contains no E 1 ,
E 1 represents a leaving group,
Q 2 represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
N(H)-propoxycarbonyl,
g) N(H)-2,2,2-trichloroethoxycarbonyl,
h) N(H)-1,1-dimethylpropynyl,
i) N(H)-1-methyl-1-phenylethoxycarbonyl,
j) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N(H)-cyclobutylcarbonyl,
l) N(H)-1-methylcyclobutylcarbonyl,
m) N(H)-vinylcarbonyl,
n) N(H)-allylcarbonyl,
o) N(H)-adamantylcarbonyl,
p) N(H)-diphenylmethylcarbonyl,
q) N(H)-cinnamylcarbonyl,
r) N(H)-formyl,
s) N(H)-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
L 3 represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 1 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X 3 and X 4 independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
Z 3 represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
18 ) Compounds of the formula (VII)
in which
A 3 represents
a) branched or straight-chain C 1 -C 5 alkoxy,
b) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) N(C 1 -C 5 alkyl) 2 ,
e) NH 2 ,
f) N(H)-L 3 or
g) O-L 3 ,
G 3 represents
a) O—Z 3 ,
b) branched or straight-chain O—C 1 -C 5 alkyl,
c) branched or straight-chain O—C 2 -C 5 alkenyl,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
e) branched or straight-chain O—C 1 -C 5 alkynyl or
f) triphenylmethoxy,
R 10 and R 11 represent
a) hydrogen,
b) substituted or unsubstituted E 1 -C 6 -C 10 mono- or bicyclic aryl,
c) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic aryl-E 1 ,
d) substituted or unsubstituted E 1 -C 5 -C 10 mono- or bicyclic heteroaryl,
e) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl-E 1 ,
f) substituted or unsubstituted E 1 -C 3 -C 6 cycloalkyl,
g) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl-E 1 ,
h) hydroxyl,
i) branched or straight-chain C 1 -C 5 alkyl,
j) branched or straight-chain C 1 -C 5 alkoxy,
k) substituted or unsubstituted O-alkylene-C 6 -C 10 mono- or bicyclic aryl- 18 F,
l) substituted or unsubstituted O-alkylene-C 5 -C 10 mono- or bicyclic heteroaryl- 18 F or
m) substituted or unsubstituted O—C 3 -C 6 cycloalkyl- 18 F,
alkylene being optionally interrupted by one or more O, S or N,
with the proviso that exactly one of the substituents R 10 or R 11 contains an E 1 and the respective other substituent contains no E 1 ,
E 1 represents a leaving group,
Q 2 represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
f) N(H)-propoxycarbonyl,
g) N(H)-2,2,2-trichloroethoxycarbonyl,
h) N(H)-1,1-dimethylpropynyl,
i) N(H)-1-methyl-1-phenylethoxycarbonyl,
j) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N(H)-cyclobutylcarbonyl,
l) N(H)-1-methylcyclobutylcarbonyl,
m) N(H)-vinylcarbonyl,
n) N(H)-allylcarbonyl,
o) N(H)-adamantylcarbonyl,
p) N(H)-diphenylmethylcarbonyl,
q) N(H)-cinnamylcarbonyl,
r) N(H)-formyl,
s) N(H)-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
L 3 represents
a) branched or straight-chain C 1 -C 5 , alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X 3 and X 4 independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
Z 3 represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
19 ) A method comprising using compounds of the formula (VII) for preparing compounds of the formula (V) or (VI):
in which
A 3 represents
a) branched or straight-chain C 1 -C 5 alkoxy,
b) branched or straight-chain hydroxy C 1 -C 5 alkoxy,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) N(C 1 -C 5 alkyl) 2 ,
e) NH 2 ,
N(H)-L 3 or
g) O-L 3 ,
G 3 represents
a) O—Z 3 ,
b) branched or straight-chain O—C 1 -C 5 alkyl,
c) branched or straight-chain O—C 2 -C 5 alkenyl,
d) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
e) branched or straight-chain O—C 1 -C 5 alkynyl or
f) triphenylmethoxy,
R 10 and R 11 represent
a) hydrogen,
b) substituted or unsubstituted E 1 -C 6 -C 10 mono- or bicyclic aryl,
c) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic aryl-E 1 ,
d) substituted or unsubstituted E 1 -C 5 -C 10 mono- or bicyclic heteroaryl,
e) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl-E 1 ,
f) substituted or unsubstituted E 1 -C 3 -C 6 cycloalkyl,
g) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl-E 1 ,
h) hydroxyl,
i) branched or straight-chain C 1 -C 5 alkyl,
j) branched or straight-chain C 1 -C 5 alkoxy,
k) substituted or unsubstituted O-alkylene-C 6 -C 10 mono- or bicyclic aryl-E 1 ,
l) substituted or unsubstituted O-alkylene-C 5 -C 10 mono- or bicyclic heteroaryl-E 1 or
m) substituted or unsubstituted O—C 3 -C 6 cycloalkyl-E 1 ,
alkylene being optionally interrupted by one or more O, S or N,
with the proviso that exactly one of the substituents R 10 or R 11 contains an E 1 and the respective other substituent contains no E 1 ,
E 1 represents a leaving group,
Q 2 represents
a) N(H)-tert-butoxycarbonyl
b) N(H)-allyloxycarbonyl,
c) N(H)-benzyloxycarbonyl,
d) N(H)-ethoxycarbonyl,
e) N(H)-methoxycarbonyl,
N(H)-propoxycarbonyl,
g) N(H)-2,2,2-trichloroethoxycarbonyl,
h) N(H)-1,1-di methylpropynyl,
i) N(H)-1-methyl-1-phenylethoxycarbonyl,
j) N(H)-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N(H)-cyclobutylcarbonyl,
l) N(H)-1-methylcyclobutylcarbonyl,
m) N(H)-vinylcarbonyl,
n) N(H)-allylcarbonyl,
o) N(H)-adamantylcarbonyl,
p) N(H)-diphenylmethylcarbonyl,
q) N(H)-cinnamylcarbonyl,
r) N(H)-formyl,
s) N(H)-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
L 3 represents
a) branched or straight-chain C 1 -C 5 alkyl,
b) branched or straight-chain C 2 -C 5 alkenyl,
c) branched or straight-chain C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl or
d) branched or straight-chain C 2 -C 5 alkynyl,
X 3 and X 4 independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
Z 3 represents a metal cation equivalent,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
20 ) Compounds of the formula (VIII)
in which
G 4 represents
a) branched or straight-chain O—C 1 -C 5 alkyl,
b) branched or straight-chain O—C 2 -C 5 alkenyl,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkynyl or
e) triphenylmethoxy,
R 12 and R 13 represent
a) hydrogen,
b) hydroxyl,
c) branched or straight-chain C 1 -C 5 alkyl,
d) branched or straight-chain C 1 -C 5 alkoxy or
e) R 14 -E 2 ,
with the proviso that exactly one of the substituents R 12 or R 13 contains an E 2 and the respective other substituent contains no E 2 ,
E 2 represents a leaving group,
R 14 represents
a) substituted or unsubstituted C 6 -C 10 mono- or bicyclic aryl,
b) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic
aryl,
c) substituted or unsubstituted C 5 -C 10 mono- or bicyclic heteroaryl,
d) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl,
f) substituted or unsubstituted C 3 -C 6 cycloalkyl,
g) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl,
h) substituted or unsubstituted O-alkylene C 5 -C 10 mono- or bicyclic aryl,
i) substituted or unsubstituted O-alkylene C 5 -C 10 mono- or bicyclic heteroaryl or
j) substituted or unsubstituted O—C 3 -C 6 cycloalkyl,
alkylene being optionally interrupted by one or more O, S or N,
Q 3 represents
a) N-tert-butoxycarbonyl
b) N-allyloxycarbonyl,
c) N-benzyloxycarbonyl,
d) N-ethoxycarbonyl,
e) N-methoxycarbonyl,
f) N-propoxycarbonyl,
g) N-2,2,2-trichloroethoxycarbonyl,
h) hydrogen,
i) N-1-methyl-1-phenylethoxycarbonyl,
j) N-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N-cyclobutylcarbonyl,
l) N-1-methylcyclobutylcarbonyl,
m) N-vinylcarbonyl,
n) N-allylcarbonyl,
o) N-adamantylcarbonyl,
p) N-diphenylmethylcarbonyl,
q) N-cinnamylcarbonyl,
r) N-formyl or
s) N-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
X 5 and X 6 independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
21 ) A method comprising using compounds of the formula (VIII) for preparing compounds of the formula (V) or (VI):
in which
G 4 represents
a) branched or straight-chain O—C 1 -C 5 alkyl,
b) branched or straight-chain O—C 2 -C 5 alkenyl,
c) branched or straight-chain O—C 1 -C 5 alkyl-(O—C 1 -C 4 alkyl) n -O—C 1 -C 4 alkyl,
d) branched or straight-chain O—C 2 -C 5 alkynyl or
e) triphenylmethoxy,
R 12 and R 13 represent
a) hydrogen,
b) hydroxyl,
c) branched or straight-chain C 1 -C 5 alkyl,
d) branched or straight-chain C 1 -C 5 alkoxy or
e) R 14 -E 2 ,
with the proviso that exactly one of the substituents R 12 or R 13 contains an E 2 and the respective other substituent contains no E 2 ,
E 2 represents a leaving group,
R 14 represents
a) substituted or unsubstituted C 6 -C 10 mono- or bicyclic aryl,
b) substituted or unsubstituted alkylene-C 6 -C 10 mono- or bicyclic aryl,
c) substituted or unsubstituted C 5 -C 10 mono- or bicyclic heteroaryl,
d) substituted or unsubstituted alkylene-C 5 -C 10 mono- or bicyclic heteroaryl,
e) substituted or unsubstituted C 3 -C 6 cycloalkyl,
f) substituted or unsubstituted alkylene-C 3 -C 6 cycloalkyl
g) substituted or unsubstituted O-alkylene C 5 -C 10 mono- or bicyclic aryl,
h) substituted or unsubstituted O-alkylene-C 5 -C 10 mono- or bicyclic heteroaryl or
i) substituted or unsubstituted O—C 3 -C 6 cycloalkyl,
alkylene being optionally interrupted by one or more O, S or N,
Q 3 represents
a) N-tert-butoxycarbonyl
b) N-allyloxycarbonyl,
c) N-benzyloxycarbonyl,
d) N-ethoxycarbonyl,
e) N-methoxycarbonyl,
0 N-propoxycarbonyl,
g) N-2,2,2-trichloroethoxycarbonyl,
h) hydrogen,
i) N-1-methyl-1-phenylethoxycarbonyl,
j) N-1-methyl-1-(4-biphenylyl)ethoxycarbonyl,
k) N-cyclobutylcarbonyl,
l) N-1-methylcyclobutylcarbonyl,
m) N-vinylcarbonyl,
n) N-allylcarbonyl,
o) N-adamantylcarbonyl,
p) N-diphenylmethylcarbonyl,
q) N-cinnamylcarbonyl,
r) N-formyl,
s) N-benzoyl,
t) N(H)-trityl,
u) N(H)-p-methoxyphenyldiphenylmethyl,
v) N(H)-di(p-methoxyphenyl)phenylmethyl,
w)
x) N-(tert-butoxycarbonyl) 2 ,
X 5 and X 6 independently of one another represent
a) branched or straight-chain C 1 -C 5 alkyl,
b) substituted or unsubstituted aryl,
c) substituted or unsubstituted alkylaryl or
d) substituted or unsubstituted heteroaryl,
where n=0, 1, 2 or 3 and
all diastereomers and enantiomers are included.
22 ) Imaging-kit, comprising compounds of the general formula VII or VIII.
23 ) Pharmaceutical composition, comprising compounds of the general formula V, VI, VII or VIII and suitable pharmaceutical carrier substances.
24 ) Compounds according to claim 1 for use as a medicament.
25 ) Compounds according to claim 1 for use for imaging in tumour disorders.
26 ) Compounds according to claim 1 for producing a medicament for imaging in tumour disorders.
27 ) Compounds according to claim 1 , characterized in that the compounds are suitable for imaging in a dosage range of 37-600 MBq.
28 ) Compounds according to claim 27 , characterized in that the compounds are particularly suitable in a dosage range of 150 MBq-370 MBq.