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

• US 8,642,638 B2
• Filed: 11/19/2009
• Issued: 02/04/2014
• 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:
  US13/129,782
• Publication Number:
  US 20110288119A1
• Time in Patent Office: 1,538 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 improve cognition.

Claims

1. A method of improving cognition in a patient suffering from Schizophrenia, comprising:

administering to said patient a daily dose in the range of between 0.1 mg to 3.0 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 the patient.

4. 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.

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 monohydrate.

6. The method of claim 5, wherein the daily dose is in the range of between 0.3 mg to 1.5 mg.

7. The method of claim 5, wherein the daily dose is in the range of between 0.7 mg to 1.25 mg.

8. The method of claim 5, wherein the daily dose is in the range of between 1.0 mg to 3.0 mg.

9. The method of claim 5, wherein the daily dose is in the range of between 1.5 mg to 2.5 mg.

10. The method of claim 5, wherein the daily dose is in the range of between 1.75 mg to 2.25 mg.

11. The method of claim 5, wherein the daily dose is in the range of between 2.0 mg to 3.0 mg.

12. The method of claim 1, wherein the schizophrenia comprises a paranoid type, a disorganized type, catatonic type, or an undifferentiated type.

13. The method of claim 12, 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.

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

administering to said patient a daily dose in the range of between 0.1 mg to 3.0 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, or a pharmaceutically acceptable salt thereof.

15. The method of claim 14, 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.

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 administered to said patient.

17. The method of claim 16, 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.

18. The method of claim 16, 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.

19. The method of claim 18, wherein the daily dose is in the range of between 0.3 mg to 1.5 mg.

20. The method of claim 18, wherein the daily dose is in the range of between 0.7 mg to 1.25 mg.

21. The method of claim 18, wherein the daily dose is in the range of between 1.0 mg to 3.0 mg.

22. The method of claim 18, wherein the daily dose is in the range of between 1.5 mg to 2.5 mg.

23. The method of claim 18, wherein the daily dose is in the range of between 1.75 mg to 2.25 mg.

24. The method of claim 18, wherein the daily dose is in the range of between 2.0 mg to 3.0 mg.

25. The method of claim 14, 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.