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Details for Patent: 6,211,245

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Details for Patent: 6,211,245

Title: Compounds active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases
Abstract:Method and compositions for treating a patient having a neurological disease or disorder, such as stroke, head trauma, spinal cord injury, spinal cord ischemia, ischemia- or hyproxia-induced nerve cell damage, epilepsy, anxiety, neuropsychiatric or cognitive deficits due to ischemia or hypoxia such as those that frequently occur as a consequence of cardiac surgery under cardiopulmonary bypass, or neurodegenerative diseases such as Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, or amyotrophic lateral sclerosis (ALS).
Inventor(s): Mueller; Alan L. (Salt Lake City, UT), Moe; Scott T. (Salt Lake City, UT)
Assignee: NPS Pharmaceuticals, Inc. (Salt Lake City, UT)
Filing Date:Nov 04, 1998
Application Number:09/186,341
Claims:1. A compound of Formula VIII: ##STR187##

wherein:

Z is selected from the group consisting of --CH.sub.2 CH.sub.2 --, --CH.sub.2 CH(CH.sub.3)--, and --CH.dbd.CH--;

X.sup.1 and X.sup.2 are independently selected from the group consisting of --F, --Cl, --CH3, --OH, and lower O-alkyl in the 1-, 3-, 7-, or 9-substituent positions;

m is independently an integer from 0 to 2;

--NHR is selected from the group consisting of --NH.sub.2, --NHCH.sub.3, and --NHC.sub.5 H;

R.sup.1 is selected from the group consisting of --H, alkyl, hydroxyalkyl, --OH, --O--alkyl, and --O--acyl, and

R.sup.2 is selected from the group consisting of --H, alkyl, hydroxyalkyl, and pharmaceutically acceptable salts and complexes thereof, wherein the compound is active at an NMDA receptor.

2. The compound of claim 1, wherein:

Z is --CH.sub.2 CH.sub.2 --;

X.sup.1 or X.sup.2 is --F, or both X.sup.1 and X.sup.2 are --F;

either R.sup.1 or R.sup.2 is methyl or both R.sup.1 and R.sup.1 are --H; and

--NHR is selected from the group consisting of --NH.sub.2 or --NHCH.sub.3.

3. A compound selected from the group consisting of ##STR188##

and pharmaceutically acceptable salts and complexes thereof.

4. The compound of claim 3, wherein said compound is ##STR189##

5. The compound of claim 3, wherein said compound is ##STR190##

6. The compound of claim 3, wherein said compound is ##STR191##

7. The compound of claim 3, wherein said compound is ##STR192##

8. The compound of claim 3, wherein said compound is ##STR193##

9. A pharmaceutical composition, comprising a compound of claim 1, and a pharmaceutically acceptable carrier.

10. A pharmaceutical composition comprising a compound of claim 2, and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition, comprising a compound selected from the group consisting of ##STR194##

and pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier.

12. The pharmaceutical composition of claim 11, wherein said compound is ##STR195##

13. The pharmaceutical composition of claim 11, wherein said compound is ##STR196##

14. The pharmaceutical composition of claim 11, wherein said compound is ##STR197##

15. The pharmaceutical composition of claim 11, wherein said compound is ##STR198##

16. The pharmaceutical composition of claim 11, wherein said compound is ##STR199##

17. A pharmaceutical composition, comprising a compound as in any of claims 1, 3, or 6, and a pharmaceutically acceptable carrier.

18. The pharmaceutical composition of claim 17, wherein said pharmaceutical composition is adapted for the treatment or a neurological disease or disorder.

19. The pharmaceutical composition of claim 17, wherein said pharmaceutical composition is adapted to provide neuroprotection to a patient.

20. The pharmaceutical composition of claim 17, wherein said compound is a hydrochloride salt.

21. The pharmaceutical composition of claim 17, wherein said compound is a hydrochloride salt.

22. The pharmaceutical composition of claim 17, wherein said compound is a hydrochloride salt.

23. A method for treating a patient having a neurological disease or disorder comprising administering a compound of claim 1.

24. A method for treating a patient having a neurological disease or disorder comprising administering a compound of claim 2.

25. A method for treating a patient having a neurological disease or disorder, comprising administering a compound selected from the group consisting of ##STR200##

and pharmaceutically acceptable salts and complexes thereof.

26. The method of claim 25, wherein said compound is selected from the group consisting of ##STR201##

and pharmaceutically acceptable salts and complexes thereof.

27. The method of claim 25, wherein said compound is ##STR202##

28. The method of claim 25, wherein said compound is ##STR203##

29. The method of claim 25, wherein said compound is ##STR204##

30. The method of claim 29, wherein said compound is ##STR205##

31. The method of claim 29, wherein said compound is ##STR206##

32. The method of any of claims 23 or 29, wherein said neurological disease or disorder is selected from the group consisting of consisting of stroke, head trauma, spinal cord injury, epilepsy, anxiety, Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

33. The method of claim 32, wherein said neurological disease or disorder is stroke.

34. The method of claim 32, wherein said neurological disease or disorder is head trauma.

35. The method of claim 32, wherein said neurological disease or disorder is spinal cord injury.

36. The method of claim 32, wherein said neurological disease or disorder is epilepsy.

37. The method of claim 32, wherein said neurological disease or disorder is anxiety.

38. The method of claim 32, wherein said neurological disease or disorder is Alzheimer's disease.

39. The method of claim 32, wherein said neurological disease or disorder is Huntington's disease.

40. The method of claim 32, wherein said neurological disease or disorder is Parkinson's disease.

41. The method of claim 32, wherein said neurological disease or disorder is amyotrophic lateral sclerosis.

42. The method of claim 33, wherein said stroke is global ischemic.

43. The method of claim 33, wherein said stroke is hemorrhagic.

44. The method of claim 33, wherein said stroke is focal ischemic.

45. A method for providing neuroprotection to a patient, comprising administering a compound as in any of claims 1, 3, or 6.
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