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US 2014/0227196 A1Published application
Porphyrin compounds and their use as mri contrast agents
AssigneesThe Hospital for Sick Children, The Governing Council of the University of Toronto
InventorsXiao-an ZHANG, Wei Ran CHENG, Inga HAEDICKE, Hai-Ling CHENG
Life of this patent
Estimating the term…
Abstract
Water soluble porphyrin compounds useful in the field of magnetic resonance imaging (MRI) as contrast agents. Particular compounds include manganese.
Claims20
A water soluble porphyrin compound of formula (A), or a salt thereof:
- wherein one or more of D, E and F is defined as in paragraphs (a) to (c):
- (a) (i) D is of the formula (LD):
- wherein:
- each LD and LD1 is independently a covalent bond or a rigid bivalent linker;
- one or the other or both of D1 and D2 is a water-solubilizing group;
- one or more of D3, D4 and D5 is a water-solubilizing group;
- and
- mD has a value of from 0 to 20;
- or
- (ii) D is of the formula (LD′):
- wherein:
- LD is a rigid trivalent linker;
- each LD1 is, independently of any other LD1, a covalent bond or a rigid bivalent linker;
- each LD2 is, independently of any other LD2, a covalent bond or a rigid bivalent linker;
- each LD3 is, independently of any other LD3, a covalent bond or a rigid bivalent linker;
- each LD4 is, independently of any other LD4, a covalent bond or a rigid bivalent linker;
- one or the other or both of D1 and D2 is a water-solubilizing group;
- one or more of D3, D4 and D5 is a water-solubilizing group;
- one or the other or both of D6 and D7 is a water-solubilizing group;
- one or more of D8, D9 and D10 is a water-solubilizing group;
- mD1 has a value of from 0 to 20;
- and
- mD2 has a value of from 0 to 20;
- (b) (i) E is of the formula (LE):
- wherein:
- each LE and LE1 is, independently, a covalent bond or a rigid bivalent linker;
- one or the other or both of E1 and E2 is a water-solubilizing group;
- one or more of E3, E4 and E5 is a water-solubilizing group;
- mE has a value of from 0 to 20;
- or
- (ii) E is of the formula (LE′):
- wherein:
- LE is a rigid trivalent linker;
- each LE1 is, independently of any other LE1, a covalent bond or a rigid bivalent linker;
- each LE2 is, independently of any other LE2, a covalent bond or a rigid bivalent linker;
- each LE3 is, independently of any other LE3, a covalent bond or a rigid bivalent linker;
- each LE4 is, independently of any other LE4, a covalent bond or a rigid bivalent linker;
- one or the other or both of E1 and E2 is a water-solubilizing group;
- one or more of E3, E4 and E5 is a water-solubilizing group;
- one or the other or both of E6 and E7 is a water-solubilizing group;
- one or more of E8, E9 and E10 is a water-solubilizing group;
- mE1 has a value of from 0 to 20;
- and
- mE2 has a value of from 0 to 20;
- (c) (i) F is of the formula (LF):
- wherein:
- each LF and LF1 is, independently, a covalent bond or a rigid bivalent linker;
- one or the other or both of F1 and F2 is a water-solubilizing group;
- one or more of F3, F4 and F5 is a water-solubilizing group;
- LF1 is a covalent bond or a rigid bivalent linker;
- and
- mF has a value of from 0 to 20;
- or
- (ii) F is of the formula (LF′):
- wherein:
- LF is a rigid trivalent linker;
- each LF1 is, independently of any other LF1, a covalent bond or a rigid bivalent linker;
- each LF2 is, independently of any other LF2, a covalent bond or a rigid bivalent linker;
- each LF3 is, independently of any other LF3, a covalent bond or a rigid bivalent linker;
- each LF4 is, independently of any other LF4, a covalent bond or a rigid bivalent linker;
- one or the other or both of F1 and F2 is a water-solubilizing group;
- one or more of F3, F4 and F5 is a water-solubilizing group;
- one or the other or both of F6 and F7 is a water-solubilizing group;
- one or more of F8, F9 and F10 is a water-solubilizing group;
- mF1 has a value of from 0 to 20;
- and
- mF2 has a value of from 0 to 20;
- and wherein:
- when D, E and F are all defined as in paragraphs (a) to (c), G is a water-solubilizing group, or C is defined as in paragraph (d):
- (d) (i) C is of the formula (LG):
- wherein:
- each LG and LG1 is, independently, a covalent bond or a rigid bivalent liner;
- one of the other or both of G1 and G2 is a water-solubilizing group;
- one or more of G3, G4 and G5 is a water-solubilizing group;
- LG1 is a covalent bond or a rigid bivalent linker;
- and
- mG has a value of from 0 to 20;
- or
- (ii) G is of the formula (LG′):
- wherein:
- LG is a rigid trivalent linker;
- each LG1 is, independently of any other LG1, a covalent bond or a rigid bivalent linker;
- each LG2 is, independently of any other LG2, a covalent bond or a rigid bivalent linker;
- each LG3 is, independently of any other LG3, a covalent bond or a rigid bivalent linker;
- each LG4 is, independently of any other LG4, a covalent bond or a rigid bivalent linker;
- one or the other or both of G1 and G2 is a water-solubilizing group;
- one or more of G3, G4 and G5 is a water-solubilizing group;
- one or the other or both of G6 and G7 is a water-solubilizing group;
- one or more of G8, G9 and G10 is a water-solubilizing group;
- mG1 has a value of from 0 to 20;
- and
- mG2 has a value of from 0 to 20;
- and
- the sum of mD, mD1, mD2, mE, mE1, mE2, mF, mF2, mG, mG1 and mG2 is from 0 to 30;
- and
- M is a paramagnetic metal ion present in at least one porphyrin ring, and may be the same or different when present in a plurality of porphyrin rings.
93 more elements
A water soluble porphyrin compound of formula (A), or a salt thereof:
- wherein:
- each of R1 to R8 and D, F, F and G is independently selected from the group consisting of:
- hydrogen, halogen, thiol, cyano, nitro, amido (—C(O)NH2), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), alkylammonium (—NR3+), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2, a C3-C20 cycloalkyl group containing a nitrogen atom in its ring wherein the cycloalkyl group is bonded to the porphyrin ring by a carbon or nitrogen atom, a C3-C20 aryl group containing a nitrogen atom in its ring, and
- wherein n is from 1 to 20;
- C1-C20 alkyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C3-C20 cycloalkyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C3-C20 heterocycloalkyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C1-C20 alkenyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C3-C20 cycloalkenyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C3-C20 heterocycloalkenyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2, alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C6 to C20 aryl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C3 to C20 heteroaryl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C7 to C20 arylalkyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C4 to C20 heteroarylalkyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C2 to C20 alkynyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C1 to C20 heteroalkyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- C2 to C20 heteroalkenyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
- and
- C2 to C20 heteroalkynyl, optionally substituted with up to 4 of any of hydroxyl, halogen, thiol, cyano, nitro, oxo (═O), carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2),
- wherein each R is independently straight chain or branched C1-C20 alkyl,
- wherein at least one of R1 to R8 and D, E, F and G is carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), amino, alkylamino (—NHR), dialkylamino (—NR2), aminoalkyl (—(C1-C20 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH).
18 more elements
Dependencies are inferred from the claim text.