Claims for Patent: 6,992,207

Summary for Patent: 6,992,207

Title:	Melphalan derivatives and their use as cancer chemotherapeutic drugs
Abstract:	The invention refers to new alkylating di- and tripeptides based on a melphalan unit, and one or two additional amino acids or amino acid derivatives, which can be used in the treatment of carcinogenic diseases. Further, the invention refers to a pharmaceutical composition comprising the alkylating peptides of the invention.
Inventor(s):	Lewensohn; Rolf (Danderyd, SE), Gullbo; Joakim (Uppsala, SE), Larsson; Rolf (Uppsala, SE), Ehrsson; Hans (Bromma, SE), Luthman; Kristina (Gothenburg, SE)
Assignee:	Oncopeptides AB (Danderyd, SE)
Application Number:	10/297,588
Patent Claims:	1. A di- or tripepetide having the formula I: ##STR00005## wherein R.sub.1 is alkyloxy, cycloalkyloxy, aryloxy, arylalkyloxy, NH.sub.2, alkylamino, cycloalkylamino, or arylamino; R.sub.2 is ##STR00006## wherein R.sub.3 is independently NH.sub.2, OH, O-alkyl, N-alkyl, O-acyl, NH-acyl, N(CH.sub.2CH.sub.2Cl ).sub.2, NO.sub.2, F, CF.sub.3 or H, and n is 1 or 2; X is ##STR00007## wherein R.sub.5 is H; R.sub.4 is a natural or modified cyclic or aromatic amino acid, or H; and pharmaceutically acceptable salts thereof. 2. A di- or tripepetide having the formula V: ##STR00008## wherein R.sub.1 is alkyloxy, cycloalkyloxy, aryloxy, arylalkyloxy, NH.sub.2, alkylamino, cycloalkylamino, or arylamino; R.sub.3 is NH.sub.2, OH, O-alkyl, N-alkyl, O-acyl, NH-acyl, N(CH.sub.2CH.sub.2Cl).sub.2, NO.sub.2, F, CF.sub.3 or H: and R.sub.4 is a natural or modified cyclic or aromatic amino acid, or H; and pharmaceutically acceptable salts thereof. 3. A method of manufacturing a medicament, comprising: formulating the peptide according to claim 1 with a pharmaceutically acceptable excipient. 4. The peptide according to claim 1, wherein R.sub.3 is F. 5. The peptide according to claim 2, wherein R.sub.1 is alkyloxy; R.sub.3 is F, CF.sub.3, H, OH, O-alkyl, NO.sub.2, N(CH.sub.2CH.sub.2Cl).sub.2, NH-acyl or NH.sub.2; and R.sub.4 is H. 6. The peptide according to claim 5, which is L-melphanyl-p-L-fluoro-phenylalanine ethyl ester or a pharmaceutically acceptable salt thereof. 7. The peptide according to claim 5, which is L-melphanyl-p-L-fluoro-phenylalanine isopropyl ester or a pharmaceutically acceptable salt thereof. 8. The peptide according to claim 2, wherein R.sub.1 is alkyloxy; R.sub.3 is F, CF.sub.3, H, OH, O-alkyl, NH-acyl, NO.sub.2, N(CH.sub.2CH.sub.2Cl).sub.2 or NH.sub.2; and R.sub.4 is a natural or modified cyclic or aromatic amino acid. 9. The peptide according to claim 8, which is L-prolin-L-melphanyl-p-fluorophenylalanine ethyl ester or a pharmaceutically acceptable salt thereof. 10. A pharmaceutical composition for the treatment of malignant tumours, comprising at least one peptide compound according to claim 1, together with at least one pharmaceutically acceptable carrier and/or excipient. 11. The pharmaceutical composition according to claim 10, for the treatment of breast cancer, lung cancer, ovarian cancer, leukemias, lymphomas and multiple myeloma. 12. A method of treating malignant tumours, comprising: administering a pharmaceutically effective dose of the peptide according to claim 1 to a subject in need thereof. 13. A method of manufacturing a medicament, comprising: formulating the peptide according to claim 2 with a pharmaceutically acceptable excipient. 14. The peptide according to claim 2, wherein R.sub.3 is F. 15. A pharmaceutical composition for the treatment of malignant tumors, comprising at least peptide compound according to claim 2, together with at least one pharmaceutically acceptable carrier and/or excipient. 16. The pharmaceutical composition according to claim 15, for the treatment of breast cancer, lung cancer, ovarian cancer, leukemias, lymphomas and multiple myeloma. 17. A method of treating malignant tumours, comprising: administering a pharmaceutically effective dose of the peptide according to claim 2 to a subject in need thereof.