Macrocylic ligands with picolinate group(s), complexes thereof and also medical uses thereof
The present invention relates to compounds, ligands, and/or complexes that are useful in medical imaging and/or in therapy, especially in cancer treatment. The present invention also relates to a pharmaceutical composition comprising said compounds, ligands, and/or complexes that are useful for medical imaging, targeting, and/or treatment of cancers. The present invention also relates to a process for preparing these compounds, ligands, and/or complexes.
1. A compound of general formula (I) or a pharmaceutically acceptable salt of general formula (I)
in which:
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 represent, independently of each other, one of the following:
H, a (C 1 -C 20 )alkyl group or a (C 1 -C 20 )alkylene-(C 6 -C 00 )aryl group, wherein said alkyl, alkylene and aryl groups optionally are substituted with one or more organic acid functions;
X 1 , X 2 and X 3 represent, independently of each other, one of the following:
H, —C(O)N(Re)(Rd), a (C 1 -C 20 )alkyl, a (C 2 -C 20 )alkenyl, a (C 2 -C 20 )alkynyl, or a (C 6 -C 10 )aryl, with Re and Rd being, independently of each other, H or a (C 1 -C 20 )alkyl group, wherein said alkyl, alkenyl and alkynyl groups optionally comprise one or more heteroatoms and/or one or more (C 6 -C 10 )arylenes in their chains and, wherein said alkyl, alkenyl and alkynyl groups optionally are substituted with a (C 6 -C 10 )aryl,
wherein said alkyl, alkenyl, alkynyl and aryl groups optionally are substituted with one or more organic acid functions;
Y 1 , Y 2 and Y 3 represent, independently of each other, a C(O)OH group or a group of formula (II), with at least one of Y 1 , Y 2 , and Y 3 , being a group of formula (II):
in which:
the radicals Ri represent, independently of each other, one of the following:
H, a halogen, N 3 , a (C 1 -C 20 )alkyl, a (C 2 -C 20 )alkenyl, a (C 2 -C 20 )alkynyl, or a (C 6 -C 10 )aryl, wherein said alkyl, alkenyl and alkynyl groups optionally comprise one or more heteroatoms and/or one or more (C 6 -C 10 )arylenes in their chains and, wherein said alkyl, alkenyl, and alkynyl groups optionally are substituted with a (C 6 -C 10 )aryl;
wherein said alkyl, alkenyl, alkynyl and aryl groups optionally are substituted with one or more organic acid functions.
2. The compound of claim 1 , wherein R 1 and R 2 , R 3 and R 4 or R 5 and R 6 represent H.
3. The compound of claim 1 , wherein the one or more heteroatoms of said alkyl, alkenyl and alkynyl groups of the radicals Ri are selected from the group consisting of N, O and S.
4. The compound of claim 1 selected from the group consisting of the following compounds:
5. A pharmaceutical composition comprising the compound of claim 1 and optionally one or more pharmaceutically acceptable excipients.
6. The pharmaceutical composition of claim 5 further comprising an iodinated oil.
7. The pharmaceutical composition of claim 6 , wherein the iodinated oil comprises ethyl esters of iodinated fatty acids of poppy oil.
8. A complex comprising the compound of claim 1 and a meta atom M.
9. A method for the therapeutic treatment of a patient suffering from cancer, the method comprising administering to said patient of the complex of claim 8 wherein the metal atom M is a radioisotope.
10. The method according to claim 9 , wherein the cancer is liver cancer.
11. A method for detecting a tumor in a patient via a medical imaging, the method comprising:
administering to said patient the complex of claim 8 ; and
conducting the medical imaging method on said administered patient thereby detecting the tumor.
12. A pharmaceutical composition comprising a complex of claim 5 and optionally one or more pharmaceutically acceptable excipients.
13. The pharmaceutical composition of claim 12 further comprising an iodinated oil.
14. The pharmaceutical composition of claim 13 , wherein the iodinated oil comprises ethyl esters of iodinated fatty acids of poppy oil.