2-(3-AMINOARYL) AMINO-4-ARYL-THIAZOLES AND THEIR USE AS C-KIT INHIBITORS

• US 20110201620A1
• Filed: 01/28/2011
• Published: 08/18/2011
• Est. Priority Date: 08/02/2002
• Status: Active Grant

• Current Assignee: A+ Science AB (A+ Science Holding AB)
• Original Assignee: A+ Science AB (A+ Science Holding AB)
• Inventors: Giethlen, Bruno, Moussy, Alain, Wermuth, Camille, Ciufolini, Marco, Kinet, Jean-Pierre
• Granted Patent: US 8,450,302 B2
• Time in Patent Office: Days
• US Class Current: 514/253.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 277/42 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 277/56 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

The present invention relates to the use of masitinib or a pharmaceutically acceptable salt thereof, and in particular of masitinib mesylate, for the preparation of a medicament for the treatment of GIST, to the use of this therapy for the treatment of GIST, and a method of treating mammals, including humans, suffering from GIST by administering to said mammal in need of such treatment an effective dose of masitinib, and in particular masitinib mesylate.

Claims

1. A method for the treatment of a subject with Gastrointestinal Stromal Tumours (GIST), wherein said method comprises the administration of an effective amount of masitinib or a pharmaceutically acceptable salt thereof to said subject.

2. The method of claim 1, wherein the treatment is for treating or preventing cancer cell metastasis.

3. The method of claim 1, wherein said treatment comprises the oral administration of masitinib or a pharmaceutically acceptable salt thereof to a subject in need thereof.

4. The method of claim 1, wherein said effective amount of masitinib or a pharmaceutically acceptable salt thereof is a daily dose depending on the patient weight.

5. The method of claim 1, wherein said effective amount of masitinib or a pharmaceutically acceptable salt thereof is a daily dose below 18 mg/kg of subject weight.

6. The method of claim 1, wherein said effective amount of masitinib or a pharmaceutically acceptable salt thereof is for a first-line therapy a daily dose from 6 mg/kg to 9 mg/kg of subject weight.

7. The method of claim 1, wherein said effective amount of masitinib or a pharmaceutically acceptable salt thereof, in particular of masitinib mesylate, is for a first-line therapy a daily dose of 7.5 mg/kg of subject weight.

8. The method of claim 1, wherein said effective amount of masitinib or a pharmaceutically acceptable salt thereof is for a second-line therapy a daily dose from 10.5 to 15 mg/kg of subject weight.

9. The method of claim 1, wherein said effective amount of masitinib or a pharmaceutically acceptable salt thereof is for a second-line therapy a daily dose of 12.5 mg/kg of subject weight.

10. The method according claim 1, wherein the daily dose is 7.5, 9 or 10.5 mg/kg of subject weight.

11. The method of claim 1, wherein said effective amount of masitinib or a pharmaceutically acceptable salt thereof is administered in two intakes a day.

20. The method of claim 1, wherein masitinib or a pharmaceutically acceptable salt thereof, in particular masitinib mesylate, inhibits the growth of imatinib-resistant cells.

21. The method of claim 1, wherein masitinib or a pharmaceutically acceptable salt thereof is administrated in combination with another tyrosine kinase inhibitor.

22. The method claim 1, wherein masitinib or a pharmaceutically acceptable salt thereof is administrated in combination with imatinib

23. The method of claim 1, wherein masitinib or a pharmaceutically acceptable salt thereof is administrated to a patient whose tumour is not treatable by surgery.

24. The method of claim 1, wherein masitinib or a pharmaceutically acceptable salt thereof is administrated as a second-line treatment therapy to a patient, whose tumour is resistant to another tyrosine kinase inhibitor, and for example imatinib.

26. The method of claim 1, wherein said subject is a human patient.

27. The method of claim 1, wherein said masitinib pharmaceutically acceptable salt is masitinib mesylate.

28. The method of claim 1, wherein said masitinib or a pharmaceutically acceptable salt thereof is administered in a composition comprising a dose of at least 50 and lower than 150 mg of masitinib or a pharmaceutically acceptable salt thereof.

29. The method of claim 1, wherein said masitinib or a pharmaceutically acceptable salt thereof is administered in a composition comprising a dose of 100 mg of masitinib or a pharmaceutically acceptable salt thereof.

30. The method of claim 1, wherein said masitinib or a pharmaceutically acceptable salt thereof is administered in a composition comprising a dose of at least 150 and lower than 400 mg, of masitinib or a pharmaceutically acceptable salt thereof.

31. The method of claim 1, wherein said masitinib or a pharmaceutically acceptable salt thereof is administered in a composition comprising a dose of 200 mg of masitinib or a pharmaceutically acceptable salt thereof.

12. A method for the treatment of a subject with a proliferative disease wherein a tyrosine kinase is affected, said subject having cells showing a mutant kit and/or mutant PDGFRA gene(s), comprising the administration of masitinib or a pharmaceutically acceptable salt thereof, in particular of masitinib mesylate.

13. The method of claim 12, wherein said kit mutation is at least one mutation in exon 9, exon 11, exon 13, or exon 17.

14. The method of claim 12, wherein said mutation is a mutation conferring resistance to a tyrosine kinase.

15. The method of claim 12, wherein said mutation is a mutation conferring resistance to imatinib drug treatment.

16. A method for the long-term treatment of a subject with Gastrointestinal Stromal Tumours (GIST), wherein said method comprises the administration on a long-term of an effective amount of masitinib or a pharmaceutically acceptable salt thereof to said subject.

17. The method of claim 16, wherein said long-term treatment is a treatment over more than 12 months.

18. The method of claim 16, wherein said long-term treatment is a treatment over more than 2 years.

19. A method for the treatment of a subject with non-pre-treated, inoperable, locally advanced or metastatic GIST, wherein said method comprises the administration of an effective amount of masitinib or a pharmaceutically acceptable salt thereof to said subject.

25. A method for the treatment of a subject having cells resistant to a treatment of a proliferative disease wherein tyrosine kinase is affected, said treatment comprises the administration of a tyrosine kinase inhibitor other than masitinib, said method comprising the steps of:

Identifying in a subject a cell resistance to a treatment by a tyrosine kinase inhibitor other than masitinib of a proliferative disease wherein tyrosine kinase is affected;

Administering masitinib or a pharmaceutically acceptable salt thereof, in particular masitinib mesylate, to said subject.