Compositions containing a ruthenium(III) complex and a heterocycle
View Patent ↗Compositions, containing a ruthenium(III) complex and a heterocycle, methods for their manufacture, medicament containing these compositions and a kit. The invention relates to a composition (A), obtained by reacting a compound of the general formula (I) M 3−n−p−2pr [RuX 6−n−p−q−2r B n (H 2 O) p (OH) q (O) r ] 2r+1 (I) with a compound of the general formula (II) B′(HX′) S . (II) Furthermore, the invention relates to a composition (B), obtained by mixing a compound of the general formula (III) (B′H) 3−n−p−2pr [RuX 6−n−p−q−2r B n (H 2 O) p (OH) q (O) r ] 2r+1 (III) with a compound of the general formula (IV) MX′. (IV)
1. A composition comprising a mixture of:
(i) a compound of the general formula (III):
(B′H) 3−n−p−2pr [RuX 6−n−p−q−2r B n (H 2 O) p (OH) q (O) r ] 2r+1 (III)
wherein each of B and B′ independently represents a monocyclic or multi cyclic basic heterocycle selected from imidazol, pyrazol, triazol or indazol, each X independently represents a halide, pseudo-halide, HCO 3 − , or RCOO − , in which R represents a substituted or unsubstituted C 1 -C 6 -alkyl or C 2 -C 6 -alkenyl or a substituted or unsubstituted aryl, n=1 or 2, r=0, and each of p and q=0 or 1, or r=0.5 and each of p and q=0 or 0.5; and
(ii) a compound of the formula (IV):
MX′ (IV)
wherein M represents an alkali metal cation or ammonia and X′ represents a halide, pseudo-halide, HCO 3 − , or RCOO − , in which R is hydrogen or a substituted or unsubstituted C 1 -C 6 -alkyl or C 2 -C 6 -alkenyl or a substituted or unsubstituted aryl, phosphate, sulphate or acetate.
2. A composition of claim 1 obtained by a process comprising reacting:
(i) a compound of the formula (I):
M 3−n−p−2pr [RuX 6−n−p−q−2r B n (H 2 O) p (OH) q (O) r ] 2r+1 (I)
wherein each M independently represents an alkali metal cation or ammonia, each B independently represents a monocyclic or multi cyclic basic heterocycle selected from imidazol, pyrazol, triazol or indazol, each X independently represents a halide, pseudo-halide, HCO 3 −, or RCOO − , in which R is a substituted or unsubstituted C 1 -C 6 -alkyl or C 2 -C 6 -alkenyl or a substituted or unsubstituted aryl, n=1 or 2, r=0, and each of p and q=0 or 1, or r=0.5 and each of p and q=0 or 0.5; and
(ii) a compound of the formula (II):
B′(HX') s (II)
wherein B′ represents a monocyclic or multi cyclic basic heterocycle selected from imidazol, pyrazol, triazol or indazol, each X′ independently represents a halide, pseudo-halide, HCO 3 − , or RCOO − , in which R is hydrogen or a substituted or unsubstituted C 1 C 6 -alkyl or C 2 -C 6 -alkenyl or a substituted or unsubstituted aryl, phosphate, sulphate, acetate, and s is an integer of 1 or more.
3. A composition according to claim 2 , wherein the compound of the formula (I) is sodium trans-[tetrachlorobis(1H-indazol)-ruthenate (III)], and wherein the compound of formula (II) is indazolium hydrochloride.
4. A composition according to claim 2 , wherein the molar ratio of the compound of the formula (I) to the compound of the formula (II) is 1:1.1.
5. A medicament comprising a composition according to claim 1 .
6. A method of treating a tumor comprising administering to a patient a composition according to claim 2 , wherein the tumor is selected from the group consisting of a breast cancer, an ovarian cancer, a lung cancer, a colorectal tumor, a prostate cancer, a melanoma, a liver cancer, an astrocytoma, a neuroblastoma, a leukemia, an epidermoid carcinoma, a cervical carcinoma, a bladder carcinoma, an endometrioma, a tongue carcinoma, a glioblastoma, a lymphoid tumor, and a renal cell carcinoma.
7. The composition according to claim 1 , further comprising a compound of the formula (II):
B′(HX') s (II)
wherein B′ represents a monocyclic or multi cyclic basic heterocycle selected from imidazol, pyrazol, triazol or indazol, each X′ independently represents a halide, pseudo-halide HCO 3 − , or RCOO − , in which R is hydrogen or a substituted or unsubstituted C 1-C 6 -alkyl or C 2 -C 6 -alkenyl or a substituted or unsubstituted aryl, phosphate, sulphate, acetate, and s is an integer of 1 or more.
8. The composition according to claim 2 , wherein B is indazol.
9. The composition according to claim 8 , wherein B′ is indazol.
10. The composition according to claim 1 , wherein B is indazol.
11. The composition according to claim 10 , wherein B′ is indazol.
12. The method according to claim 6 , wherein the tumor is selected from the group consisting of an ovarian cancer, a lung cancer, a colorectal tumor, a prostate cancer, a melanoma, a liver cancer, an epidermoid carcinoma, a bladder carcinoma, an endometrioma, a tongue carcinoma, and a renal cell carcinoma.
13. The method according to claim 12 , wherein the tumor is an ovarian cancer or a colorectal tumor.
14. A method of treating a tumor comprising administering to a patient a composition according to claim 1 , wherein the tumor is selected from the group consisting of a breast cancer, an ovarian cancer, a lung cancer, a colorectal tumor, a prostate cancer, a melanoma, a liver cancer, an astrocytoma, a neuroblastoma, a leukemia, an epidermoid carcinoma, a cervical carcinoma, a bladder carcinoma, an endometrioma, a tongue carcinoma, a glioblastoma, a lymphoid tumor, and a renal cell carcinoma.
15. The method according to claim 14 , wherein the tumor is selected from the group consisting of an ovarian cancer, a lung cancer, a colorectal tumor, a prostate cancer, a melanoma, a liver cancer, an epidermoid carcinoma, a bladder carcinoma, an endometrioma, a tongue carcinoma, and a renal cell carcinoma.
16. The method according to claim 15 , wherein the tumor is an ovarian cancer or a colorectal tumor.