Analogues of etoposide for the treatment of tumours
View Patent ↗Compounds for treatment of a patient having a tumour that is metastatic and/or that reduces an organ function, wherein the compounds are of the general formula: wherein X is O, NH and S, wherein n is 0, 1 or 2, wherein R 1 and R 2 are H, methyl or ethyl, or together form a group CR 3 R 4 , and wherein R 3 and R 4 are H, methyl or ethyl.
1. A method of treating tumor in a subject in need thereof, wherein said method comprises administering to the subject a compound of formula (I)
wherein
X is selected from the group consisting of O, NH and S,
n is 0, 1 or 2, and
R 1 and R 2 are independently selected from the group consisting of H, methyl, and ethyl, or together form a group CR 3 R 4 wherein R 3 and R 4 are independently selected from the group consisting of H, methyl and ethyl,
wherein the tumor is metastatic and/or that reduces an organ function; and,
wherein the tumor is resistant to etoposide.
2. The method of claim 1 , wherein said method comprises administering to the subject a compound selected from the group consisting of
3. The method of claim 1 , wherein the subject is a human.
4. The method of claim 1 , wherein the tumor is resistant to treatment with a therapeutic protein or a chemotherapeutic drug exclusive of the compound of formula (I)
wherein
X is selected from the group consisting of O, NH and S,
n is 0, 1 or 2, and
R 1 and R 2 are independently selected from the group consisting of H, methyl, and ethyl, or together form a group CR 3 R 4 wherein R 3 and R 4 are independently selected from the group consisting of H, methyl and ethyl.
5. The method of claim 1 , wherein the tumor is a solid tumor.
6. The method of claim 5 , wherein the tumor is selected from the group consisting of adenocarcinoma, hypopharynx cancer, lung cancer, diffuse large cell lymphoma, Burkitt's lymphoma, Hodgkin lymphoma, Non-Hodgkin lymphoma, histiocytic lymphoma, lymphatic lymphoma, acute T-cell leukemia, pre-B-acute lymphoblastic leukemia, gall bladder cancer, bile duct carcinoma, thymus carcinoma, urothelium carcinoma, testicular cancer, prostate cancer, bladder cancer, brain tumor, AIDS-related Kaposi's sarcoma, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, ovarian cancer, breast cancer, and unknown primary origin (CUP) syndrome.
7. The method of claim 1 , wherein the treatment leads to a stagnation of tumor growth or a remission of the tumor.
8. The method of claim 1 , wherein said tumor reduces an organ function.
9. The method of claim 1 , wherein the tumor expresses at least one of CES1 and CES2.
10. The method of claim 9 , wherein the fraction of CES1 and/or CES2 expressing cells of the tumor is 0.50% or higher.
11. The method of claim 1 , further comprising administering to the subject a second therapeutic drug compound.
12. The method of claim 1 , wherein the compound of formula (I) is administered to the subject intravenously.