Metal complex compounds as photosensitizers for photodynamic therapy

A compound of formula I, including any stereoisomer or E/Z isomer thereof,

• wherein:
• M is a metal cation selected from the group consisting of:
• Fe2+, Ru2+, Os2+, Co3+, Rh2+, Rh3+, Ir3+, Ni2+, Pd2+, Pt2+, and Pt4+;
• y=1, 2, or 3;
• and z=0, 1, or 2;
• on the proviso that y+z=2 when M is Ni2+, Pd2+ or Pt2+, and y+z=3 when M is Fe2+, Ru2+, Os2+, Co3+, Rh2+, Rh3+, Ir3+, or Pt4+;
• m=0, 1, 2, 3, or 4;
• radicals T and T′ at each occurrence are each one a radical independently selected from the group consisting of:
• H and (C1-C3)-alkyl;
• radicals P3, P5, P6, Q3, Q4, Q5, Q6, R3, R5, R6, and R8 at each occurrence are each one a radical independently selected from the group consisting of:
• H, (C1-C3)-alkyl, (C3-C6)-cycloalkyl, CH═CHR, CF3, CHF2, CH2F, CF2CF3, F, Cl, Br, I, OR, C(═O)OR, O(C═O)R, C(═O)NR, NRC(═O)R′, NRR′, phenyl, mono-substituted phenyl, di-substituted phenyl, and tri-substituted phenyl;
• wherein substituents on the phenyl ring are attached to any of the possible substitution positions, and they are independently selected from the group consisting of:
• F, Cl, Br, I, NO2, (C1-C3)-alkyl, OH, O[(C1-C3)-alkyl], NH2, NH[(C1-C3)-alkyl], and N[(C1-C3)-alkyl]2;
• wherein when m>1 and radical R3 is CH2 a 6-membered ring may be formed between the CH2 of R3 and the T′ radical closest D the coumarin backbone provided that T′=CH2, thus providing a compound of formula IV;
• radical R7 is H, NO2, OR, NRR′, N(CH2COOH)2, N(CH2CH2SO3H)2, N(CH2CONHCH2CH2NMe2)2, or:
• an unsubstituted, a mono-(R)-substituted, a di-(R,R′)-substituted, or a tri-(R,R′,R″)-substituted radical of each one of the heterocyclic radicals 1-aziridinyl, 1-azetidinyl, 1-pyrrolidinyl, I-piperidinyl, 4-morpholinyl, or 1-piperazinyl;
• alternatively R6, R7, and R8 form together the bicycle system of the accompanying formula, wherein V1, V2, V3, V4, V5, V6, V7, V8, V9, V10, V11, and V12 are each one a radical independently selected from the group consisting of H and (C1-C3)-alkyl;
• radical R4 is H, (C1-C3)-alkyl, (C3-C6)-cycloalkyl, CF3, CHF2, CH2F, CF2CF3, F, Cl, Br, I, OR, C(═O)OR, O(C═O)R, C(═O)NR, NRC(═O)R′, NRR′, phenyl, a mono-(R)-substituted phenyl, a di-(R, R′)-substituted phenyl, a tri-(R, R′, R″)-substituted phenyl, or a radical CE1E2E3;
• wherein:
• E1 and E2 are radicals independently selected from the group consisting of:
• H, F, Cl, Br, I, OR, NRR′, NO2, (C1-C3)-alkyl, phenyl, and a mono-(R)-substituted phenyl;
• and E3 is OH, O[(C1-C3)-alkyl], or a radical of the accompanying formula wherein p=0, 1, 2, 3 or 4;
• and D1 and D2 at each occurrence are radicals independently selected from the group consisting of H, O[CH2]q—X, S[CH2]q—X, and N[[CH2]q—X]2, being q=1 or 2, and X=F, Cl, Br or I.
• or a radical of the accompanying formula wherein p=1, 2, 3 or 4;
• and D3 is a radical independently selected from the group consisting of H, H(C═O), [(C1-C3)-alkyl](C═O), (OH)2P(═O)O—CH2—O(C═O), or (PhO)(OH)P(═O)
• Lig at each occurrence is a bidentate ligand independently selected from the group consisting of ligands of accompanying formulae:
• Lig 1, Lig 2, Lig 3, Lig 4, Lig 5, Lig 6, Lig 7, Lig 8, Lig 9, Lig 10, Lig 11, Lig 12, and Lig 13;
• wherein G is either an N atom, or a C atom with one negative charge that is formed in situ from a C—H when a H+ is lost in the formation of the carbon-metal bond;
• and wherein R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20 and R21 at each occurrence is each one a radical independently selected from the group consisting of:
• H, (C1-C3)-alkyl, phenyl, and mono-, di- and tri-substituted phenyl, substituents attached to the phenyl ring being independently selected from F, Cl, Br, I, OR and NRR′;
• and
• A is an anion from a pharmaceutically acceptable acid;
• n being an integer or fractional number whereby the compound of formula I is electrically neutral;
• wherein R, R′ and R″ at each one of the above-mentioned occurrences are each one a radical independently selected from the group consisting of:
• H, F, Cl, Br, I, NO2, (C1-C3)-alkyl, OH, O[(C1-C3)-alkyl], NH2, NH[(C1-C3)-alkyl], and N[(C1-C3)-alkyl]2.