Tricarbonyl complexes with tridentate chelators for myocardium imaging
View Patent ↗Chelators of the formulae (I), (II) and (III) and tricarbonyl complexes of radioisotopes of Tc and Re bound to them, for use in myocardial imaging.
1. A compound comprising Formula (I), (II), or (III):
wherein,
n is an integer selected from 1 or 2, and
at least one of R1, R2, R3, and R4 is a linear group of the type —R x —O—R Y or a macrocyclic ether group,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted, and
provided that when the tridentate chelator is of the type of formula (I), when R1 is —R x —O—R Y wherein R Y is substituted, and R2, R3, and R4 are each hydrogen, R Y is not substituted apically by a further tris(pyrazolyl)methane moiety; and
when R1 is —R x —O—R Y and R2, R3, and R4 are each hydrogen, R1 cannot be —CH 2 —O—CH 2 —(p- t Bu-C 6 H 4 ).
2. The compound of claim 1 , wherein the compound is complexed with a 99m Tc radioisotope.
3. A compound comprising Formula (I):
wherein,
at least one of R1, R2, R3, and R4 is a linear or macrocyclic ether group of the type —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5), respectively,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted,
provided that when R1 is —R x —O—R Y wherein R Y is substituted, and R2, R3, and R4 are each H, R Y is not substituted apically by a further tris(pyrazolyl)methane moiety; and when R1 is —R x —O—R Y and R2, R3, and R4 are each H, R1 cannot be —CH 2 —O—CH 2 —(p- t Bu-C 6 H 4 ).
4. The composition of claim 3 , wherein R1 is chosen from CH 2 OCH 3 , CH 2 OCH 2 CH 3 , and CH 2 OCH 2 CH 2 CH 3 .
5. The composition of claim 3 , wherein R2, R3, and R4 are hydrogen.
6. The composition of claim 3 , wherein R1 is hydrogen; R2 and R4 are C 1 to C 3 alkyl; and R3 is the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
7. The composition of claim 6 , wherein R2 and R4 are methyl, and R3 is CH 2 CH 2 OCH 3 .
8. The composition of claim 3 , wherein R1 and R3 are hydrogen, and R2 and R4 are the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
9. The composition of claim 8 , wherein R2 and R4 are CH 2 OCH 3 .
10. The composition of claim 3 , wherein R1 is hydrogen and R2, R3, and R4 are the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
11. The composition of claim 10 , wherein R2, R3, and R4 are CH 2 OCH 3 .
12. The composition of claim 3 , wherein R1, R2, and R4 are hydrogen and R3 is the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
13. The composition of claim 12 , wherein R3 is CH 2 OCH 3 .
14. The composition of claim 12 , wherein R3 is CH 2 OCH 2 CH 3 .
15. The composition of claim 3 , wherein R2, R3, and R4 are hydrogen.
16. A compound comprising Formula (II):
wherein,
n is an integer selected from 1 or 2, and
at least one of R1, R2, R3, and R4 is a linear or macrocyclic ether group of the type —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5), respectively,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted.
17. The composition of claim 16 , wherein n is equal to 1; R1 is the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl; and R2, R3, and R4 are hydrogen.
18. The composition of claim 17 , wherein R1 is CH 2 CH 2 OCH 3 .
19. A compound comprising Formula (III):
wherein,
n is an integer selected from 1 or 2, and
at least one of R1, R2, R3, and R4 is a linear or macrocyclic ether group of the type —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5), respectively,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted.
20. The composition of claim 19 , wherein n is equal to 2; R1, R2, and R4 are the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl; and R3 is hydrogen.
21. The composition of claim 20 , wherein R1 is CH 2 CH 2 OCH 3 , and R2 and R4 are CH 2 OCH 3 .