Methods of modulating c-kit tyrosine protein kinase function with indolinone compounds

• US 20020010203A1
• Filed: 12/22/2000
• Published: 01/24/2002
• Est. Priority Date: 12/22/1999
• Status: Abandoned Application

• Current Assignee: Sugen Incorporated (Pharmacia Corp.)
• Original Assignee: Sugen Incorporated (Pharmacia Corp.)
• Inventors: McMahon, Gerald, Lipson, Ken
• Application Number:
  US09/741,842
• Publication Number:
  US 20020010203A1
• Time in Patent Office: Days
• US Class Current: 514/418
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

The present invention concerns compounds and their use to inhibit the activity of a receptor tyrosine kinase. The invention is preferably used to treat cell proliferative disorders such as cancers characterized by over-activity or inappropriate activity c-kit kinase.

Claims

1. A method for treating or preventing an abnormal condition in an organism, wherein said abnormal condition is associated with an aberration in a signal transduction pathway mediated by a c-kit kinase, wherein said method comprises the step of administering to said organism a therapeutically effective amount of an indolinone compound that modulates, in vitro, the catalytic activity of c-kit kinase.

2. The method of claim 1 wherein said aberration in said signal transduction pathway is mediated by an interaction between said c-kit kinase and a natural binding partner, and said indolinone compound modulates, in vitro, the interaction between said c-kit kinase and said natural binding partner.

3. The method of claim 1 wherein said abnormal condition is a disease related to inappropriate c-kit kinase signal transduction.

4. The method of claim 1, wherein said abnormal condition is selected from the group consisting of mastocytosis, the presence of one or more mast cell tumors, asthma, and allergy associated chronic rhinitis.

5. The method of claim 1, wherein said abnormal condition is selected from the group consisting of small cell lung cancer, non-small cell lung cancer, acute myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, a colorectal carcinoma, a gastric carcinoma, a gastrointestinal stromal tumor, a testicular cancer, a glioblastoma, and an astrocytoma.

6. The method of claim 1 wherein said organism is a mammal.

7. The method of claim 1 wherein said organism is a human.

8. The method of any one of claims 1, 2 and 3 wherein said indolinone compound is a compound of the structure set forth in Formula I:

9. The method of any one of claims 1, 2 and 3 wherein said indolinone compound is a compound of the structure set forth in Formula II:

10. The method of any one of claims 1, 2 and 3 wherein said indolinone compound is selected from the group consisting of compounds