Porphyrin compounds and their use as MRI contrast agents

A water soluble porphyrin compound of formula (A), or a salt thereof:

• wherein:
• each of R1 to R8 and D, E, 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+), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2, a C3-C6 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-C6 aryl group containing a nitrogen atom in its ring, and
• wherein n is from 1 to 20;
• C1-C6 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, guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C3-C6 cycloalkyl, optionally substituted with up to 6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C3-C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C1-C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C3-C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C3-C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C3 to C6 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);
• C4 to C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C2 to C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• C1 to C6 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 C6 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-C6 alkyl)NH2), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), amido (—C(O)NH2);
• and
• C2 to C6 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-C6 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 two of D, E, F and G are carboxyl, sulfonate, phosphate (—OPO3H2), alkylphosphate (—OPO3RH), phosphonate (—PO3H2), alkylphosphonate (—PO3RH), phosphinate (—PO2H), alkylphosphinate (—PO2R), guanidine (—NHC(NH)NH2), alkyl guanidine (—NHC(NH)NRH), and
• and wherein M is a paramagnetic metal ion.