N-methylaminomethyl isoindole compounds and compositions comprising and methods of using the same

• US 20080214615A1
• Filed: 09/14/2007
• Published: 09/04/2008
• Est. Priority Date: 09/15/2006
• Status: Active Grant

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: Chen, Roger Shen-Chu, Muller, George W.
• Granted Patent: US 8,648,096 B2
• Time in Patent Office: Days
• US Class Current: 514/323
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/04 for inducing labour or abortion; Uterotonics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

This invention relates to N-methylaminomethyl-isoindoline compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

Claims

1. A compound of formula (I):

2. The compound of claim 1 having a structure of formula (II):

3. The compound of claim 2, wherein X is C═

O.

4. The compound of claim 2, wherein R is methyl or ethyl.

5. The compound of claim 2, wherein R is NHR′

, and wherein R¹ is (C₆-C₁₀)aryl, optionally substituted with one or more (C₁-C₆)alkyl or (C₁-C₆)alkoxy.

6. The compound of claim 5, wherein said alkyl or alkoxy is substituted with one or more of halogen.

7. The compound of claim 2, wherein R is a 5 to 10 membered heteroaryl.

8. The compound of claim 2, wherein X is CH₂.

9. The compound of claim 8, wherein R is methyl or ethyl.

10. The compound of claim 2, wherein R is NHR′

, and wherein R′

is (C₆-C₁₀)aryl, optionally substituted with one or more (C₁-C₆)alkyl, (C₁-C₆)alkoxy, or halogen.

11. The compound of claim 10, wherein R¹ is phenyl, optionally substituted with one or more methyl, methoxy, trifluoromethyl, or chloride.

12. The compound of claim 2, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the compound is:

13. A pharmaceutical composition comprising a compound of claim 1.

14. A method of treating, managing or preventing a disease or disorder which comprises administering to a patient in need of such treatment, management or prevention a therapeutically or prophylactically effective amount of a compound of claim 1, wherein the disease or disorder is cancer, a disorder associated with angiogenesis, pain, macular degeneration or a related syndrome, a skin disease, a pulmonary disorder, an asbestos-related disorder, a parasitic disease, an immunodeficiency disorder, a CNS disorder, CNS injury, atherosclerosis or a related disorder, dysfunctional sleep or a related disorder, hemoglobinopathy or a related disorder, or a TNFα

related disorder.

15. The method of claim 14, wherein the disease is cancer.

16. The methods of claim 15, wherein the cancer is hematologic or solid cancer.

17. The method of claim 14, which further comprises administration of one or more additional active agents.

18. The method of claim 14, wherein the compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is administered orally or parenterally.

19. A single unit dosage form comprising a compound of claim 1.

20. The single unit dosage form of claim 19, which is suitable for oral or parenteral administration.

21. The single unit dosage form of claim 20, which is suitable for oral administration.

22. The single unit dosage form of claim 21, which is a tablet or a capsule.