1-12. (canceled)
13. An organometallic compound of the general formula (I),
MR1R2R3R4R5R6\u2003\u2003(I),
which may be charged or neutral, and which may be present in the form of a salt andor an optically resolved enantiomer,
in which,
M is a transition metal selected from the group of Ru, Os, Rh, and Ir;
R1, R2, R3, R4, R5, R6 are neutral or charged ligands of the transition metal, whereby two, three or more of the ligands R1-R6 may be present in the form of one or more single compounds, the single compound being
a bi-, tri- or polydentate compound, andor,
an alkene, alkyne, cyclopentadienyl, andor an arene, the alkene, alkyne cyclopentadienyl, andor an arene being optionally substituted and optionally comprising one or more heteroatoms;
and,
in which at least one bioactive organic compound selected from inhibitors of resistance pathways, related compounds, andor derivatives of any of the fore-mentioned, is present in the organometallic compound, whereby the bioactive organic compound is directly attached to the metal, thus constituting at least one of the ligands selected from R1-R6, andor is covalently bound to any of the ligands selected from R1-R6.
14. The organometallic compound of claim 13, in which the bioactive organic compound is an inhibitor of resistance selected from Glutathione S-transferase inhibitors, \u25a1-Glutamyl Cysteine Synthetase inhibitors, multidrug resistance proteinP-glycoproteins inhibitors, and inhibitors of cell signalling pathways.
15. The organometallic compound of claim 13, in which three neighbouring ligands selected from R1-R6, are present in the form of an alkene, alkyne, cyclopentadienyl andor arene, optionally substituted and optionally comprising one or more heteroatoms, the alkene, alkyne andor arene optionally constituting the bioactive compound andor optionally being bound to the bioactive compound.
16. The organometallic compound of claim 13, which comprises the structure of
in which,
A is an arene, optionally substituted and optionally comprising one or more heteroatoms;
R18, R19, R20, are ligands of the central ruthenium atom which are, independently of each other, selected from halogens andor N-, O-, S-, or P-donor ligands;
R17 is an optional residue selected from an alkyl, alkenyl, alkynyl, aryl, optionally substituted and optionally comprising one or more heteroatoms;
whereby the at least one bioactive organic compound constitutes at least one selected from R17-R20, or is covalently linked to any of the R17-R20, with the proviso that residues selected from R17-R20, which constitute the bioactive organic compound, or which are covalently bound the bioactive organic compound, are not halogens.
17. The organometallic compound of claim 13, in which three neighbouring ligands of R1-R6 are formed by an arene of the formula (VI)
in which R8, R9, R10, R11, R12, R13 are, independently of each other, hydrogen, alkyl, alkenyl, alkynyl, aryl, optionally substituted and optionally comprising one or more heteroatoms, and in which two or more residues selected from R9, R9, R10, R11, R12, R13 may be covalently linked with each other thus forming a bi- or tri-, or polycyclic system, and in which any of the residues R8, R9, R10, R11, R12, R13 optionally constitutes or is optionally bound to the bioactive compound.
18. The organometallic compound of claim 13, in which at least one of R1, R2, R3, R4, R5, R6 is a residue suitable of increasing the solubility of the complex of formula (I) in water.
19. The organometallic compound of claim 13, in which any of R1, R2, R3, R4, R5, has the formula (XIII),
P R14R15R16\u2003\u2003(XIII),
in which,
R8, R9, R10 may be the same or different, are each C1-C6 alkyl, alkenyl, alkynyl, aryl, optionally substituted and optionally comprising one or more heteroatoms, or R8, R9, R10 may together with the phosphorous atom form a cycloalkyl group, such group being optionally heterocyclic.
20. The organometallic compound of claim 13, wherein two or three ligands selected from R1, R2, R3, R4, R5, and R6 form a single \u25a15 or \u25a16-ligand, respectively, to the transition metal M, and wherein the bioactive compound is covalently connected to said \u25a16 or \u25a15-ligand.
21. The organometallic compound of claim 13, wherein the bioactive compound is selected from:
an inhibitor of Glutathione S-transferase inhibitor selected from ethacrynic acid, peptidomimetics based on gluthatione, p-chlorophenoxyisobutyrate, Gossypol, indomethacin, non-steroidal anti-inflammatory compounds based on ibuprofen and ketoprofen, misonidazole, Piriprost, Sulfasalazine, and derivatives of these;
an inhibitor of y-Glutamyl Cysteine Synthetase selected from sulfoxime-based compounds such as buthinone sulfoxime and methinone sulfoxime, S-sulfocysteine, S-sulfohomocysteine, cystamine, and derivatives of these;
an inhibitor of the multidrug resistance protein selected from the group of quinidine, vinblastine, terfernadine, tamoxifen, verapamil, cyclosporin, amitriptyline, progesterone, and derivatives of these.
an inhibitors of a cell signaling pathway selected from the group of pleurotin, azelaic acid, bischloroethylnitrosourea, palmarumycin, and derivatives of these.
22. A method for treating andor preventing cancer andor metastasis, the method comprising the step of administering to an individual an effective amount an organometallic compound of the general formula (I),
MR1R2R3R4R5R6\u2003\u2003(I),
which may be charged or neutral, and which may be present in the form of a salt andor an optically resolved enantiomer,
in which,
M is a transition metal selected from the group of Ru, Os, Rh, and Ir;
R1, R2, R3, R4, R5, R6 are neutral or charged ligands of the transition metal, whereby two, three or more of the ligands R1-R6 may be present in the form of one or more single compounds, the single compound being
a bi-, tri- or polydentate compound, andor,
an alkene, alkyne, cyclopentadienyl, andor an arene, the alkene, alkyne cyclopentadienyl, andor an arene being optionally substituted and optionally comprising one or more heteroatoms;
and,
in which at least one bioactive organic compound selected from inhibitors of resistance pathways, related compounds, andor derivatives of any of the fore-mentioned, is present in the organometallic compound, whereby the bioactive organic compound is directly attached to the metal, thus constituting at least one of the ligands selected from R1-R6, andor is covalently bound to any of the ligands selected from R1-R6.
23. The method of claim 22, which is a method for specifically preventing andor treating metastasis.
24. The method of claim 22, in which the bioactive organic compound is an inhibitor of resistance selected from Glutathione S-transferase inhibitors, O-Glutamyl Cysteine Synthetase inhibitors, multidrug resistance proteinP-glycoproteins inhibitors, and inhibitors of cell signalling pathways.
25. The method of claim 22, in which three neighbouring ligands selected from R1-R6, are present in the form of an alkene, alkyne, cyclopentadienyl andor arene, optionally substituted and optionally comprising one or more heteroatoms, the alkene, alkyne andor arene optionally constituting the bioactive compound andor optionally being bound to the bioactive compound.
26. The method of claim 22, wherein the organometallic compound comprises the structure of formula (III),
in which,
A is an arene, optionally substituted and optionally comprising one or more heteroatoms;
R18, R19, R20, are ligands of the central ruthenium atom which are, independently of each other, selected from halogens andor N-, O-, S-, or P-donor ligands;
R17 is an optional residue selected from an alkyl, alkenyl, alkynyl, aryl, optionally substituted and optionally comprising one or more heteroatoms;
whereby the at least one bioactive organic compound constitutes at least one selected from R17-R20, or is covalently linked to any of the R17-R20, with the proviso that residues selected from R17-R20, which constitute the bioactive organic compound, or which are covalently bound the bioactive organic compound, are not halogens.
27. The method of claim 22, in which three neighbouring ligands of R1-R6 are formed by an arene of the formula (VI)
in which R8, R9, R10, R11, R12, R13 are, independently of each other, hydrogen, alkyl, alkenyl, alkynyl, aryl, optionally substituted and optionally comprising one or more heteroatoms, and in which two or more residues selected from R8, R9, R10, R11, R12, R13 may be covalently linked with each other thus forming a bi- or tri-, or polycyclic system, and in which any of the residues R8, R9, R10, R11, R12, R13 optionally constitutes or is optionally bound to the bioactive compound.
28. The method of claim 22, in which at least one of R1, R2, R3, R4, R5, R6 is a residue suitable of increasing the solubility of the complex of formula (I) in water.
29. The method of claim 22, in which any of R1, R2, R3, R4, R5, R6 has the formula (XIII),
P R14R15R16\u2003\u2003(XIII),
in which,
R8, R9, R10 may be the same or different, are each C1-C6 alkyl, alkenyl, alkynyl, aryl, optionally substituted and optionally comprising one or more heteroatoms, or R8, R9, R10 may together with the phosphorous atom form a cycloalkyl group, such group being optionally heterocyclic.
30. The method of claim 22, wherein the bioactive compound is selected from:
an inhibitor of glutathione S-transferase selected from ethacrynic acid, peptidomimetics based on gluthatione, p-chlorophenoxyisobutyrate, Gossypol, indomethacin, non-steroidal anti-inflammatory compounds based on ibuprofen and ketoprofen, misonidazole, piriprost, sulfasalazine, and derivatives of these;
an inhibitor of y-Glutamyl Cysteine Synthetase selected from sulfoxime-based compounds such as buthinone sulfoxime and methinone sulfoxime, S-sulfocysteine, S-sulfohomocysteine, cystamine, and derivatives of these;
an inhibitor of the multidrug resistance protein selected from the group of quinidine, vinblastine, terfernadine, tamoxifen, verapamil, cyclosporin, amitriptyline, progesterone, and derivatives of these.
an inhibitors of a cell signaling pathway selected from the group of pleurotin, azelaic acid, bischloroethylnitrosourea, palmarumycin, and derivatives of these.
31. The method of claim 22, wherein two or three ligands selected from R1, R2, R3, R4, R5, and & form a single \u03b7 5 or \u03b7 6-ligand, respectively, to the transition metal M, and wherein the bioactive compound is covalently connected to said \u03b7 6 or \u03b7 5-ligand.
32. A method for reducing resistance of cancers andor metastasis against anti-cancer drugs, the method comprising the step of administrating an organometallic compound of the general formula (I),
MR1R2R3R4R5R6\u2003\u2003(I),
which may be charged or neutral, and which may be present in the form of a salt andor an optically resolved enantiomer,
in which,
M is a transition metal selected from the group of Ru, Os, Rh, and Ir;
R1, R2, R3, R4, R5, R6 are neutral or charged ligands of the transition metal, whereby two, three or more of the ligands R1-R6 may be present in the form of one or more single compounds, the single compound being
a bi-, tri- or polydentate compound, andor,
an alkene, alkyne, cyclopentadienyl, andor an arene, the alkene, alkyne cyclopentadienyl, andor an arene being optionally substituted and optionally comprising one or more heteroatoms;
and,
in which at least one bioactive organic compound selected from inhibitors of resistance pathways, related compounds, andor derivatives of any of the fore-mentioned, is present in the organometallic compound, whereby the bioactive organic compound is directly attached to the metal, thus constituting at least one of the ligands selected from R1-R6, andor is covalently bound to any of the ligands selected from R1-R6.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A system comprising:
a media content processing subsystem configured to:
receive media content through a network from a media content provider;
provide the media content to a viewer;
process a flagging request from the viewer, said flagging request designating a scene within a media content instance of the media content as a flagged scene; and
generate an indicator to be temporarily displayed as an overlay on said flagged scene on a display device in communication with said media content processing subsystem indicating that said scene has been flagged;
automatically generate an actionable data module corresponding to said flagged scene in response to said flagging request;
wherein said actionable data module comprises:
a media content identifier;
date and time of said flagged scene; and
additional content corresponding to said flagged scene, said additional content including at least one of an outtake, an alternative program ending, a director’s cut, a commercial for a product shown in said flagged scene, a cast photograph;
wherein said additional content is included with said media content received from the media content provider.
2. The system of claim 1, wherein said media content processing subsystem is further configured to update said actionable data module with data located on said network; and wherein the updating includes requesting from and receiving from said network updated additional content corresponding to said flagged scene.
3. The system of claim 2, wherein said additional content comprises one or more links to content located on said network.
4. The system of claim 1, further comprising:
the media content provider configured to provide said media content processing subsystem with a data stream comprising said media content instance of the media content;
wherein said additional content is at least in part derived from said data stream substantially simultaneously with said scene being flagged from said media content instance of the media content in said data stream.
5. The system of claim 1, wherein said media content processing subsystem comprises a storage device, and wherein said additional content comprises one or more links to content stored within said storage device.
6. The system of claim 1, wherein said media content processing subsystem comprises at least one of a set-top box, home communication terminal, digital home communication terminal, stand-alone personal video recorder, digital video disc player, video-enabled phone, and personal computer.
7. The system of claim 1, wherein said media content instance comprises at least one of a television program, pay-per-view content, video-on-demand content, Internet content, digital video disc content, and audio programming content.
8. The system of claim 1, wherein said additional content comprises at least one of descriptive information corresponding to said media content instance, purchasing options corresponding to one or more of said products displayed in said flagged scene, one or more links to web content, recording options, and one or more key words corresponding to said flagged scene.
9. The system of claim 1, wherein said media content processing subsystem is further configured to generate one or more graphical user interfaces configured to provide a user with access to said additional content corresponding to said flagged scene.
10. The system of claim 1, further comprising:
a user input device configured to communicate with said media content processing subsystem;
wherein said user input device is configured to generate said flagging request.
11. The system of claim 1, further comprising:
one or more access devices configured to communicate with said media content processing subsystem;
wherein said access devices are configured to access said additional content corresponding to said flagged scene.
12. The system of claim 1, wherein said media content processing subsystem is further configured to customize one or more options available to a user of said media content processing subsystem, wherein said customization is based on said actionable data module.
13. An apparatus comprising:
a storage device; and
a processor communicatively coupled to said storage device, said processor configured to
receive a media content instance through a network from a media content provider;
process a flagging request received from a viewer while viewing the media content instance, said flagging request designating a scene within the media content instance as a flagged scene;
generate an indicator to be temporarily displayed as an overlay on said flagged scene on a display device in communication with said media content processing subsystem indicating that said scene has been flagged;
automatically generate an actionable data module corresponding to said flagged scene in response to said flagging request; and
store said actionable data module within said storage device;
wherein said actionable data module comprises:
a media content identifier;
date and time of said flagged scene; and
additional content corresponding to said flagged scene, said additional content including at least one of an outtake, an alternative program ending, a director’s cut, a commercial for a product shown in said flagged scene, a cast photograph, and advertiser information;
wherein said additional content is included with said media content received from the media content provider.
14. The apparatus of claim 13, wherein said processor is further configured to update said actionable data module with data located on said network; and wherein the updating includes requesting from and receiving from said network updated additional content corresponding to said flagged scene.
15. The system of claim 1, wherein said media content processing subsystem is further configured to receive at least one key word into the actionable data module, and at least one of provide access to additional content associated with said at least one key word, provide a link to users who flag media content having said at least one key word, and automatically record other media content having said at least one key word.
16. The system of claim 2, wherein said updated additional content is pinged for latency, and any content that has a latency that does not meet predefined transmission standards of said network is excluded from the updated additional content.
17. The apparatus of claim 13, further comprising:
a receiving device configured to receive a data stream comprising said media content instance;
wherein said additional content is at least in part derived from said data stream substantially simultaneously with said scene being flagged from said media content instance of the media content in said data stream.
18. The apparatus of claim 13, wherein said additional content comprises one or more links to content stored within said storage device.
19. The apparatus of claim 13, wherein said additional content comprises at least one of descriptive information corresponding to said media content instance, purchasing options corresponding to one or more of said products displayed in said flagged scene, one or more links to web content, recording options, and one or more key words corresponding to said flagged scene.
20. The apparatus of claim 13, further comprising a graphics engine, wherein said graphics engine is configured to generate one or more graphical user interfaces configured to provide a user with access to said additional content corresponding to said flagged scene.
21. A method comprising:
receiving a media content instance through a network from a media content provider;
receiving from a viewer of the media content instance a flagging request, said flagging request designating a scene within the media content instance as a flagged scene;
processing said flagging request; and
generating an indicator to be temporarily displayed as an overlay on said flagged scene on a display device in communication with said media content processing subsystem indicating that said scene has been flagged;
automatically generating, in a media content processing subsystem, an actionable data module corresponding to said flagged scene in response to said flagging request;
wherein said actionable data module comprises:
a media content identifier;
date and time of said flagged scene; and
additional content corresponding to said flagged scene, said additional content including at least one of an outtake, an alternative program ending, a director’s cut, a commercial for a product shown in said flagged scene, a cast photograph, and advertiser information;
wherein said additional content is included with said media content received from the media content provider.
22. The method of claim 21, further comprising updating said actionable data module with data located on a network; and wherein the updating includes requesting from and receiving from said network updated additional content corresponding to said flagged scene.
23. The method of claim 22, wherein said additional content comprises one or more links to content located on said network.
24. The method of claim 21, wherein said additional content comprises at least one of descriptive information corresponding to said media content instance, purchasing options corresponding to one or more of said products displayed in said flagged scene, one or more links to web content, recording options, and one or more key words corresponding to said flagged scene.
25. The method of claim 21, further comprising generating one or more graphical user interfaces configured to provide a user with access to said additional content corresponding to said flagged scene.