Dihydropteridinones for the treatment of cancer diseases
Disclosed is the use of a compound of general Formula (1), optionally in form of its tautomers, racemates, enantiomers, diastereomers and the mixtures thereof and optionally in form of the pharmacologically acceptable acid addition salts, solvates, hydrates, polymorphs, physiologically functional derivatives or prodrugs thereof, for the preparation of a pharmaceutical composition for the treatment of diseases characterized by abnormal cell proliferation in a human or non-human mammalian body by inhibition of polo like kinases as mitotic regulators.
1. A method of treating cancer selected from the group consisting of carcinomas, sarcomas, melanomas, myeloma, hematologic neoplasias, lymphomas and childhood cancers said method comprises administering to a patient a therapeutically effective amount of a compound selected from the group consisting of the compounds of Formula shown in the following Table
Config.
Example
R 1
R 2
R 1 or R 2
27
H
R
44
H
R
55
H
R
58
H
R
102
H
R
103
H
R
105
H
R
110
H
R
115
H
R
133
H
R
134
H
R
234
H
R
240
H
R
and
46
H
R
Example
R 3
R 4
L n —R 5 m
27
44
H
55
58
102
103
105
110
115
133
134
234
240
and
46
wherein the abbreviations X 1 , X 2 , X 3 , X 4 and X 5 used in the Table in each case denote a link to a position in the general Formula shown in the Table instead of the corresponding groups R 1 , R 2 , R 3 , R 4 and L-R 5 , optionally in form of the pharmacologically acceptable acid addition salts thereof.
2. The method according to claim 1 , wherein the cancer hematologic neoplasm is leukemia.
3. The method according to claim 1 wherein the compound is
Konfig. R 1
Bsp.
R 1
R 2
od. R 2
R 3
R 4
L n —R 5 m
46
H
R
wherein the abbreviations X 1 , X 2 , X 3 , X 4 and X 5 used in the Table denote a link to a position in the general Formula shown in the Table instead of the corresponding groups R 1 , R 2 , R 3 , R 4 and L-R 5 , optionally in form of the pharmacologically acceptable acid addition salts thereof.
4. The method according to claim 1 wherein the compound is
Konfig. R 1
Bsp.
R 1
R 2
od. R 2
R 3
R 4
L n —R 5 m
110
H
R
wherein the abbreviations X 1 , X 2 , X 3 , X 4 and X 5 used in the Table denote a link to a position in the general Formula shown in the Table instead of the corresponding groups R 1 , R 2 , R 3 , R 4 and L-R 5 , optionally in form of the pharmacologically acceptable acid addition salts thereof.
5. The method of claim 1 , wherein the carcinomas, sarcomas, melanomas, myeloma, hematologic neoplasias, lymphomas and childhood cancers are selected from the group consisting of central nervous system tumours, bronchial and mediastinal tumours, tumours of the gastrointestinal tract, gynaecological cancers, urinary tract and testicular cancers, tumours of endocrine tissue, Ewing-sarcoma, osteosarcoma, osteogenic sarcoma, chondrosarcoma, synovial sarcoma, leiomyosarcoma, rhabdomyosarcoma, mesothelial sarcoma, mesothelioma, fibrosarcoma, angiosarcoma, hemangioendothelioma, liposarcoma, glioma, astrocytoma, myxosarcoma, malignant fibrous histiocytoma, mesenchymous, mixed mesodermal tumour, neuroblastoma, melanoma, nodular and lentigo-maligna melanoma, immunocytoma myeloma, plasmocytoma myeloma, multiple myeloma, leukemia, acute or chronic leukemia of myeloid, Hodgkin-lymphoma or T- and B-cell non-Hodgkin-lymphomas.