Patent
The present invention is directed towards new 18 F-folate radiopharmaceuticals, wherein the 18 F isotope F is linked via a prosthetic group, more specifically via a prosthetic group having a saccharide group, such as a cyclic mono- or oligosaccharide, preferably based on a pyranoside or furanoside, which is covalently linked to the glutamate portion of a folate or derivative thereof, a method of their preparation, as well as their use in diagnosis and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.
1. A compound of one of formulae Va, Vb or Vc:
including tautomer, enantiomer and racemate forms thereof,
wherein
R 5 represents H or C(1-4)alkyl
R 3 and R 4 are, independently of each other: H, C(1-4)alkyl or —COR′,
R′ represents H or C(1-4)alkyl,
m is 1, 2 or 3,
r has a value of 1 to 7,
Y 2 is O, N or S,
B 2 is H, or a protecting group,
R″ is H or a straight-chain or branched C(1-8)alkyl, which is unsubstituted or substituted by at least one CN, Hal, or NO 2 ,
Sp is a spacer which is a straight-chain or branched C(1-8)alkyl, which is unsubstituted or wherein at least one of the —CH 2 — groups is substituted with —OH, —NHR′, or —COOR′, wherein R′ represents H or C(1-8)alkyl,
L 1 ′ is a covalent bond or a straight-chain or branched C(1-6)alkyl, wherein one or more of the non-adjacent CH 2 groups may independently be replaced by a group selected from —O—, —CO—O—, —O—CO—, —NR′″—, —NR′″—CO—, and —CO—NR′″,
R′″ represents H or C(1-8)alkyl,
q is 0, 1, 2, 3 or 4,
R 9 is H or C(1-8)alkyl, and
R 10 and R 11 are, independently of each other: H, —OH, or —OC(1-8)alkyl.
2. The compound according to claim 1 , wherein m is 2.
3. The compound according to claim 1 , wherein q is 0.
4. A pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically acceptable carrier.
5. The compound according to claim 1 , having one of the formulae VIIIa, VIIIb or VIIIc:
wherein
Y 3 and Y 4 are, independently of each other: selected from H and C(1-4)alkyl, and
Y 5 is selected from H, C(1-4)alkyl or —COR′, and
R′ is H or C(1-4)alkyl.
6. The compound according to claim 1 , which is of formula Va.
7. The compound according to claim 1 , which is of formula Vb.
8. The compound according to claim 1 , which is of formula Vc.
9. The compound according to claim 5 , which is of formula VIIIa.
10. The compound according to claim 5 , which is of formula VIIIb.
11. The compound according to claim 5 , which is of formula VIIIc.
12. The compound according to claim 5 , wherein m is 2.
13. The compound according to claim 5 , wherein q is 0.