Treatment of cognitive disorders with (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof

• US 8,569,354 B2
• Filed: 11/12/2012
• Issued: 10/29/2013
• Est. Priority Date: 11/19/2008
• Status: Expired due to Fees

• Current Assignee: Forum Pharmaceuticals Inc.
• Original Assignee: Envivo Pharmaceuticals, Inc.
• Inventors: Chesworth, Richard, Shapiro, Gideon, Koenig, Gerhard
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Ivanova, Svetlana M
• Application Number:
  US13/674,290
• Publication Number:
  US 20130137717A1
• Time in Patent Office: 351 Days
• Field of Search: None
• US Class Current: 514/412
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

(R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide has been found to have procognitive effects in humans at unexpectedly low doses. Thus, (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof can be used at unexpectedly low doses to improve cognition.

Claims

1. A method of improving cognition in α

patient suffering from Schizophrenia or Alzheimer'"'"'s disease, comprising;

administering to said patient a daily dose of 3 mg, 2.70 mg, 2.50 mg, 2.25 mg, 2 mg, 1.75 mg, 1.50 mg, 1.25 mg, 1 mg, 0.7 mg, 0.5 mg, 0.3 mg, or 0.1 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is:

(R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride;

(R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate;

or (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride solvate.

3. The method of claim 2, wherein the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is administered to said patient.

4. The method of claim 3, wherein the daily dose is 1 mg, 2 mg, or 3 mg.

5. The method of claim 3, wherein the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride.

6. The method of claim 3, wherein the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate.

7. The method of claim 6, wherein the daily dose is 1 mg.

8. The method of claim 6, wherein the daily dose is 2 mg.

9. The method of claim 6, wherein the daily dose is 3 mg.

10. The method of claim 1, wherein the patient is suffering from Schizophrenia.

11. The method of claim 10, wherein the schizophrenia comprises a paranoid type, a disorganized type, catatonic type, or an undifferentiated type.

12. The method of claim 10, wherein the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, or pharmaceutically acceptable salt thereof, is administered as a pharmaceutical composition.

13. The method of claim 1, wherein the patient is suffering from Alzheimer'"'"'s disease.

14. The method of claim 13, wherein the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, or pharmaceutically acceptable salt thereof, is administered as a pharmaceutical composition.

15. A method of improving cognition in a patient suffering from Schizophrenia or Alzheimer'"'"'s disease, comprising:

administering to said patient a pharmaceutical composition comprising a daily dose of 3 mg, 2.70 mg, 2.50 mg, 2.25 mg, 2 mg, 1.75 mg, 1.50 mg, 1.25 mg, 1 mg, 0.7 mg, 0.5 mg, 0.3 mg, or 0.1 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, or a pharmaceutically acceptable salt thereof.

16. The method of claim 15, wherein the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is:

(R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride;

(R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate;

or (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride solvate.

17. The method of claim 16, wherein the pharmaceutical composition comprises the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide.

18. The method of claim 17, wherein the daily dose is 1 mg, 2 mg, or 3 mg.

19. The method of claim 17, wherein the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride.

20. The method of claim 17, wherein the pharmaceutically acceptable salt of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate.

21. The method of claim 20, wherein the daily dose is 1 mg.

22. The method of claim 20, wherein the daily dose is 2 mg.

23. The method of claim 20, wherein the daily dose is 3 mg.

24. The method of claim 15, wherein the patient is suffering from Schizophrenia.

25. The method of claim 24, wherein the schizophrenia comprises a paranoid type, a disorganized type, catatonic type, or an undifferentiated type.

26. The method of claim 15, wherein the patient is suffering from Alzheimer'"'"'s disease.