Compositions containing and methods of using N-acyl-1H-aminoindenes

• US 6,737,547 B1
• Filed: 09/15/1999
• Issued: 05/18/2004
• Est. Priority Date: 12/31/1998
• Status: Expired due to Fees

• Current Assignee: Teva Pharmaceutical Industries Limited
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Cohen, Sasson, Nachman, Rachel, Speiser, Tzipora, Sklarz, Benjamin
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US09/397,633
• Time in Patent Office: 1,707 Days
• Field of Search: 514/480, 514/481, 514/615, 514/629, 560/27, 560/28, 564/215, 564/222
• US Class Current: 564/215
• CPC Class Codes: C07C 233/03 with carbon atoms of carboxamide groups bound to hydrogen atoms
• CPC Class Codes: C07C 233/06 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 233/14 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 2602/08 the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 271/24 with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring

Abstract

The present invention provides novel aminoindenes having the structure:

wherein n is 1 or 2, R¹ is hydrogen, linear or branched chain C₁-C₈ alkyl or linear or branched chain C₁-C₈ alkoxy and R² is hydrogen or a halogen. Such compounds may be used to treat neurodegenerative conditions such as Alzheimer'"'"'s disease, head trauma, stroke, hypoxia, anoxia, epilepsy, convulsions, seizures.

Claims

1. A pharmaceutical composition comprising a compound having the structure:

wherein n is 1 or 2, R¹ is hydrogen, a linear or branched chain C₁-C₈ alkyl or a linear or branched chain C₁-C₈ alkoxy and R² is hydrogen or a halogen and a pharmaceutically acceptable carrier selected for a particular route of administration, the administration being selected from the group consisting of oral, intravenous, intraperitoneal, intramuscular, subcutaneous, intra-articular, intra-nasal, intra-thecal, intra-dermal, transdermal and inhalation.

2. The pharmaceutical composition of claim 1, wherein the halogen is chlorine.

7. A method of treating a subject suffering from a disorder selected from the group consisting of Alzheimer'"'"'s disease, head trauma, stroke, hypoxia, anoxia, epilepsy, convulsions, or seizures which comprises administering to the subject an amount of the pharmaceutical composition of claim 1 effective to treat the disorder in the subject.

8. The method of claim 7, wherein the disorder is Alzheimer'"'"'s disease.

9. The method of claim 7, wherein the disorder is head trauma.

10. The method of claim 7, wherein the disorder is stroke.

11. The method of claim 7, wherein the disorder is hypoxia.

12. The method of claim 7, wherein the disorder is anoxia.

13. The method of claim 7, wherein the disorder is epilepsy.

14. The method of claim 7, wherein the disorder is convulsions.

15. The method of claim 7, wherein the disorder is seizures.

16. The method of claim 7, wherein the administering comprises oral, parenteral, topical, transdermal, rectal, nasal, or buccal administration.

22. The compound of claim 16 having the structure:

32. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 22 and a pharmaceutically acceptable carrier.

33. The method of claim 7, wherein the amount is an amount from about 12.5 mg/kg to about 150 mg/kg.

3. A compound having the structure:

wherein n is 1 or 2, R¹ is hydrogen, a linear or branched chain C₁-C₈ alkyl or a linear or branched chain C₁-C₈ alkoxy and R² is hydrogen or a halogen;

provided that when n is 1 and R¹ is isobutyl, R² cannot be H, and that when n is 2, R¹ and R² both cannot be hydrogen.

4. The compound of claim 3, wherein the halogen is chlorine.

5. The compound of claim 3 selected from the group consisting of:

N-formyl-3-amino-1H-indene;

N-acetyl-3-amino-6-chloro-1H-indene;

N-formyl-6-chloro-3-amino-1H-indene; and

N-methoxycarbonyl-3-amino-1H-indene.

23. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier.

24. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 4 and a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 and a pharmaceutically acceptable carrier.

34. The compound of claim 3 having the structure:

35. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 34 and a pharmaceutically acceptable carrier.

6. The compound of 3 claim having the structure:

26. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 6 and a pharmaceutically acceptable carrier.

17. A compound having the structure:

wherein n is 1 or 2, R¹ is hydrogen, a linear or branched chain C₁-C₈ alkyl or a linear or branched chain C₁-C₈ alkoxy and R² is hydrogen or a halogen;

provided that when n is 1 and R¹ is isobutyl, R² cannot be H, that when n is 2, R¹ and R² both cannot be hydrogen, and that when R¹ is a methyl group, R² cannot be hydrogen.

18. The compound of claim 17 selected from the group consisting of:

N-formyl-3-amino-1H-indene;

N-acetyl-3-amino-6-chloro-1H-indene;

N-formyl-6-chloro-3-amino-1H-indene; and

N-methoxycarbonyl-3-amino-1H-indene.

19. The compound of claim 17 having the structure:

20. The compound of claim 17 having the structure:

21. The compound of claim 17 having the structure:

27. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 17 and a pharmaceutically acceptable carrier.

28. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 18 and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 19 and a pharmaceutically acceptable carrier.

30. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 20 and a pharmaceutically acceptable carrier.

31. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 21 and a pharmaceutically acceptable carrier.