IMIDAZOPYRAZINE SYK INHIBITORS

• US 20120220582A1
• Filed: 04/06/2012
• Published: 08/30/2012
• Est. Priority Date: 12/08/2008
• Status: Active Grant

• Current Assignee: Kronos Bio, Inc.
• Original Assignee: Gilead Connecticut, Inc. (Gilead Sciences Inc.)
• Inventors: CURRIE, Kevin S., MITCHELL, Scott A.
• Granted Patent: US 8,450,321 B2
• Time in Patent Office: Days
• US Class Current: 514/233.2
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/107 with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: C07D 498/04 Ortho-condensed systems
• CPC Class Codes: C07D 498/08 Bridged systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

Claims

1. A compound having the structure:

2. A pharmaceutical composition comprising

the compound of claim 1;

and

at least one pharmaceutically acceptable vehicle selected from the group consisting of carriers, adjuvants, and excipients.

3. A method for treating a patient having a disease, comprising

administering to the patient the compound of claim 1.

4. The method of claim 3, wherein the disease is selected from the group consisting of cancer, an allergic disorder, an inflammatory disease, an autoimmune disease, and an acute inflammatory reaction.

5. The method of claim 3, wherein the disease is leukemia or lymphoma.

6. The method of claim 5, wherein the disease is selected from the group consisting of B-cell lymphoma, Hodgkin'"'"'s lymphoma, non-Hodgkin'"'"'s lymphoma, hairy cell leukemia, multiple myeloma, chronic myelogenous leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphocytic leukemia.

7. The method of claim 3, wherein the disease is selected from the group consisting of rheumatoid arthritis, allergic rhinitis, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), multiple sclerosis, inflammatory bowel disease, Crohn'"'"'s disease, ulcerative colitis, systemic lupus erythematosus, and polycystic kidney disease.

8. The method of claim 3, wherein the compound is administered orally, intravenously, intramuscularly, or parenterally.

9. The method of claim 3, wherein the compound is administered orally.

10. A method for determining the presence of Syk kinase in a sample, comprising

contacting the sample with the compound of claim 1;

and

detecting a level of Syk activity in the sample.