1,7-diaryl-1,6-heptadiene-3,5-dione derivatives, methods for the production and use thereof

A method for photodynamic inactivation of microorganisms on or within a patient, wherein the method comprises the following steps:

• (A) bringing microorganisms on or within a patient into contact with at least one photosensitizer, wherein the photosensitizer is at least one 1,7-diaryl-1,6-heptadiene-3,5-dione derivative with formula (100)
• and/or with formula (101):
• or respectively a pharmacologically acceptable salt and/or ester and/or complex thereof,
• wherein Q3, Q3a, Q4 and Q4a, respectively independently of each other, represent one substituted or unsubstituted, monocyclic or polycyclic aromatic residue or one substituted or unsubstituted, monocyclic or polycyclic heteroaromatic residue,
• wherein K represents hydrogen or a cation, and
• wherein Mz+ represents a cation of a metal or boron, wherein z is the formal oxidation number of the metal M or boron and z represents a whole number from 1 to 7, and wherein
• (a1) at least one of the residues Q3, Q3a, Q4 and Q4a, respectively independently of each other, is an unsubstituted, monocyclic or polycyclic heteroaromatic residue, which has at least 5 ring atoms, wherein the ring atoms contain at least one carbon atom and at least one nitrogen atom which optionally can be protonated, or
• (a2) at least one of the residues Q3, Q3a, Q4 and Q4a, respectively independently of each other, is substituted with at least one organic residue W1, wherein the at least one organic residue W1 has the general formula (4), (5), (6), (7), (8):
• -(C(D)(E))h-X, (4)
• -A-(C(D)(E))h-X, (5)
• -(C(D)(E))k-aryl-(C(D)(E))l-X, (6)
• -A-(C(D)(E))k-aryl-(C(D)(E))l-X, (7)
• -((C(D)(E))m-A)p-(C(D)(E))n-X, (8)
• -A-((C(D)(E))m-A)p-(C(D)(E))n-X, (9),
• wherein h represents a whole number from 1 to 20, wherein k and l, respectively independently of each other, represents a whole number from 0 to 10, and wherein m, n and p, respectively independently of each other, represent a whole number from 1 to 6 and
• wherein A, respectively independently of each other, represents oxygen or sulphur,
• wherein D and E, respectively independently of each other, represent hydrogen, halogen, G-R(I), or G-C(=G)-R(II), wherein G, respectively independently of each other, represents oxygen or sulphur, and wherein the residues R(I) and R(II), respectively independently of each other, represent hydrogen, methyl, ethyl, n-propyl, n-butyl, n-pentyl, phenyl or benzyl, wherein phenyl and benzyl may be unsubstituted or substituted,
• wherein aryl represents a substituted or unsubstituted aromatic group or a substituted or unsubstituted heteroaromatic group which does not contain a nitrogen atom,
• wherein X, respectively independently of each other, is an organic residue which (i) contains at least one neutral nitrogen atom which can be protonated, or (ii) at least one positively charged nitrogen atom or (iii) at least one positively charged phosphorus atom, and
• wherein the residues R1, R2, R3, R4 and R5, respectively independently of each other, represent hydrogen, halogen, alkyl containing 1 to 12 C atoms, cycloalkyl containing 1 to 12 C atoms, alkylaryl containing 1 to 12 C atoms, aryl containing 5 to 20 C atoms, ether containing 2 to 12 C atoms or glycol containing 2 to 12 C atoms,
• or wherein
• (b) the residue R3 is an organic residue W2, wherein the one organic residue W2 has the general formula (4), (5), (6), (7), (8), (9), or (10):
• -(C(D)(E))h-X, (4)
• -A-(C(D)(E))h-X, (5)
• -(C(D)(E))k-aryl-(C(D)(E))l-X, (6)
• -A-(C(D)(E))k-aryl-(C(D)(E))l-X, (7)
• -((C(D)(E))m-A)p-(C(D)(E))n-X, (8)
• -A-((C(D)(E))m-A)p-(C(D)(E))n-X, (9),
• -(-C(D)=C(E)-)r-X, (10),
• and
• wherein, optionally, at least one of the residues Q3, Q3a, Q4 and Q4a, respectively independently of each other, is substituted with at least one organic residue W1 which has the general formula (4), (5), (6), (7), (8), or (9),
• wherein h represents a whole number from 1 to 20, wherein k and l, respectively independently of each other, represents a whole number from 0 to 10 and wherein m, n, p, and r, respectively independently of each other, represent a whole number from 1 to 6, and
• wherein A, respectively independently of each other, represents oxygen or sulphur,
• wherein D and E, respectively independently of each other, represent hydrogen, halogen, G-R(I), or G-C(=G)-R(II), wherein G, respectively independently of each other, represents oxygen or sulphur, and wherein the residues R(I) and R(II), respectively independently of each other, represent hydrogen, methyl, ethyl, n-propyl, n-butyl, n-pentyl, phenyl or benzyl, wherein phenyl and benzyl may be unsubstituted or substituted,
• wherein aryl represents a substituted or unsubstituted aromatic group or a substituted or unsubstituted heteroaromatic group which does not contain a nitrogen atom,
• wherein X, respectively independently of each other, is an organic residue which (i) contains at least one neutral nitrogen atom which can be protonated, (ii) contains at least one positively charged nitrogen atom or (iii) contains at least one positively charged phosphorus atom, and
• wherein the residues R1, R2, R4 and R5, respectively independently of each other, represent hydrogen, halogen, alkyl containing 1 to 12 C atoms, alkylaryl containing 1 to 12 C atoms, aryl containing 5 to 20 C atoms, ether containing 2 to 12 C atoms or glycol containing 2 to 12 C atoms;
• and
• (B) irradiating the microorganisms and the at least one photosensitizer with electromagnetic radiation of a suitable wavelength and energy density to inactivate said microorganisms.

A pharmaceutical composition comprising:

• (A) at least one 1,7-diaryl-1,6-heptadiene-3,5-dione derivative with formula (100)
• and/or with formula (101)
• or respectively a pharmacologically acceptable salt and/or ester and/or complex thereof,
• wherein the residues Q3, Q3a, Q4 and Q4a, respectively independently of each other, represent one substituted or unsubstituted, monocyclic or polycyclic aromatic residue or one substituted or unsubstituted, monocyclic or polycyclic heteroaromatic residue,
• wherein K represents hydrogen or a cation, and
• wherein Mz+ represents a cation of a metal or boron, wherein z is the formal oxidation number of the metal M or boron and z represents a whole number from 1 to 7, and wherein
• (a1) at least one of the residues Q3, Q3a, Q4 and Q4a, respectively independently of each other, is an unsubstituted, monocyclic or polycyclic heteroaromatic residue, which has at least 5 ring atoms, wherein the ring atoms contain at least one carbon atom and at least one nitrogen atom which optionally can be protonated, or
• (a2) at least one of the residues Q3, Q3a, Q4 and Q4a, respectively independently of each other, is substituted with at least one organic residue W1, wherein the at least one organic residue W1 has the general formula (4), (5), (6), (7), (8), or (9):
• -(C(D)(E))h-X, (4)
• -A-(C(D)(E))h-X, (5)
• -(C(D)(E))k-aryl-(C(D)(E))l-X, (6)
• -A-(C(D)(E))k-aryl-(C(D)(E))l-X, (7)
• -((C(D)(E))m-A)p-(C(D)(E))n-X, (8)
• -A-((C(D)(E))m-A)p-(C(D)(E))n-X, (9),
• wherein h represents a whole number from 1 to 20, wherein k represents a whole number from 0 to 10, wherein l represents a whole number from 0 to 10, and wherein m, n and p, respectively independently of each other, represent a whole number from 1 to 6, and
• wherein A, respectively independently of each other, represents oxygen or sulphur,
• wherein D and E, respectively independently of each other, represent hydrogen, halogen, G-R(I), or G-C(=G)-R(II), wherein G, respectively independently of each other, represents oxygen or sulphur, and wherein the residues R(I) and R(II), respectively independently of each other, represent hydrogen, methyl, ethyl, n-propyl, n-butyl, n-pentyl, phenyl or benzyl, wherein phenyl and benzyl may be unsubstituted or substituted,
• wherein aryl represents a substituted or unsubstituted aromatic group or a substituted or unsubstituted heteroaromatic group which does not contain a nitrogen atom,
• wherein X, respectively independently of each other, is an organic residue which (i) contains at least one neutral nitrogen atom which can be protonated, or (ii) contains at least one positively charged nitrogen atom, or (iii) contains at least one positively charged phosphorus atom, and
• wherein the residues R1, R2, R3, R4 and R5, respectively independently of each other, represent hydrogen, halogen, alkyl containing 1 to 12 C atoms, cycloalkyl containing 1 to 12 C atoms, alkylaryl containing 1 to 12 C atoms, aryl containing 5 to 20 C atoms, ether containing 2 to 12 C atoms or glycol containing 2 to 12 C atoms,
• or wherein
• (b) the residue R3 is an organic residue W2, wherein the one organic residue W2 has the general formula (4), (5), (6), (7), (8), (9), or (10):
• -(C(D)(E))h-X, (4)
• -A-(C(D)(E))h-X, (5)
• -(C(D)(E))k-aryl-(C(D)(E))l-X, (6)
• -A-(C(D)(E))k-aryl-(C(D)(E))l-X, (7)
• -((C(D)(E))m-A)p-(C(D)(E))n-X, (8)
• -A-((C(D)(E))m-A)p-(C(D)(E))n-X, (9),
• -(-C(D)=C(E)-)r-X, (10),
• and
• wherein, optionally, at least one of the residues Q3, Q3a, Q4 and Q4a, respectively independently of each other, is substituted with at least one organic residue W1 which has the general formula (4), (5), (6), (7), (8), or (9),
• wherein h represents a whole number from 1 to 20, wherein k represents a whole number from 0 to 10, wherein l represents a whole number from 0 to 10, and wherein m, n, p, and r, respectively independently of each other, represent a whole number from 1 to 6, and
• wherein A, respectively independently of each other, represents oxygen or sulphur,
• wherein D and E, respectively independently of each other, represent hydrogen, halogen, G-R(I), or G-C(=G)-R(II), wherein G, respectively independently of each other, represents oxygen or sulphur, and wherein the residues R(I) and R(II), respectively independently of each other, represent hydrogen, methyl, ethyl, n-propyl, n-butyl, n-pentyl, phenyl or benzyl, wherein phenyl and benzyl may be unsubstituted or substituted,
• wherein aryl represents a substituted or unsubstituted aromatic group or a substituted or unsubstituted heteroaromatic group which does not contain a nitrogen atom,
• wherein X, respectively independently of each other, is an organic residue which (i) contains at least one neutral nitrogen atom which can be protonated, (ii) contains at least one positively charged nitrogen atom, or (iii) contains at least one positively charged phosphorus atom, and
• wherein the residues R1, R2, R4 and R5, respectively independently of each other, represent hydrogen, halogen, alkyl containing 1 to 12 C atoms, alkylaryl containing 1 to 12 C atoms, aryl containing 5 to 20 C atoms, ether containing 2 to 12 C atoms or glycol containing 2 to 12 C atoms;
• and
• (B) one or more physiologically acceptable excipients.