Claims for Patent: 7,214,695

Summary for Patent: 7,214,695

Title:	Compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding
Abstract:	Kinetic stabilization of the native state of transthyretin is an effective mechanism for preventing protein misfolding. Because transthyretin misfolding plays an important role in transthyretin amyloid diseases, inhibiting such misfolding can be used as an effective treatment or prophylaxis for such diseases. Treatment methods, screening methods, as well as specific transthyretin stabilizing compounds are disclosed.
Inventor(s):	Kelly; Jeffery W. (La Jolla, CA), Powers; Evan T. (La Jolla, CA), Razavi; Hossein (Danbury, CT)
Assignee:	The Scripps Research Institute (La Jolla, CA)
Application Number:	10/741,649
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,214,695
Patent Claims:	1. A compound of formula ##STR00068## or a pharmaceutically acceptable salt thereof, wherein Ar is, 3,5-difluorophenyl, 2,6-difluorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-(trifluoromethyl)phenyl, or 3-(trifluoromethyl)phenyl. 2. The compound of claim 1 that is 4-Carboxy-2-(3,5-difluorophenyl)-benzoxazole; 4-Carboxy-2-(2,6-difluorophenyl)-benzoxazole; 4-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole; 4-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole; 4-Carboxy-2-(3,5-dichlorophenyl)-benzoxazole; 4-Carboxy-2-(2,6-dichlorophenyl)-benzoxazole; 5-Carboxy-2-(3,5-difluorophenyl)-benzoxazole; 5-Carboxy-2-(2,6-difluorophenyl)-benzoxazole; 5-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole; 5-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole; 5-Carboxy-2-(3,5-dichlorophenyl)-benzoxazole; 5-Carboxy-2-(2,6-dichlorophenyl)-benzoxazole; 6-Carboxy-2-(3,5-difluorophenyl)-benzoxazole; 6-Carboxy-2-(2,6-difluorophenyl)-benzoxazole; 6-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole; 6-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole; 6-Carboxy-2-(3,5-dichlorophenyl)-benzoxazole; 6-Carboxy-2-(2,6-dichlorophenyl)-benzoxazole; 7-Carboxy-2-(3,5-difluorophenyl)-benzoxazole; 7-Carboxy-2-(2,6-difluorophenyl)-benzoxazole; 7-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole; 7-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole; 7-Carboxy-2-(3,5-dichlorophenyl)-benzoxazole; 7-Carboxy-2-(2,6-dichlorophenyl)-benzoxazole; or. 3. The compound of claim 1 that is 2-(3,5-Dichloro -phenyl)-benzoxazole-6-carboxylic acid. 4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier. 5. The pharmaceutical composition of claim 4 that is formulated for single dosage administration. 6. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier. 7. The pharmaceutical composition of claim 6 that is formulated for single dosage administration. 8. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier. 9. The pharmaceutical composition of claim 8 that is formulated for single dosage administration. 10. The compound of claim 1 that is 4-Carboxy-2-(3,5-difluorophenyl) -benzoxazole. 11. The compound of claim 1 that is 4-Carboxy-2-(2,6-difluorophenyl) -benzoxazole. 12. The compound of claim 1 that is 4-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole. 13. The compound of claim 1 that is 4-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole. 14. The compound of claim 1 that is 4-Carboxy-2-(3,5-dichlorophenyl) -benzoxazole. 15. The compound of claim 1 that is 4-Carboxy-2-(2,6-dichlorophenyl) -benzoxazole. 16. The compound of claim 1 that is 5-Carboxy-2-(3,5-difluorophenyl) -benzoxazole. 17. The compound of claim 1 that is 5-Carboxy-2-(2,6-difluorophenyl) -benzoxazole. 18. The compound of claim 1 that is 5-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole. 19. The compound of claim 1 that is 5-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole. 20. The compound of claim 1 that is 5-Carboxy-2-(3,5-dichlorophenyl) -benzoxazole. 21. The compound of claim 1 that is 5-Carboxy-2-(2,6-dichlorophenyl) -benzoxazole. 22. The compound of claim 1 that is 6-Carboxy-2-(3,5-difluorophenyl) -benzoxazole. 23. The compound of claim 1 that is 6-Carboxy-2-(2,6-difluorophenyl) -benzoxazole. 24. The compound of claim 1 that is 6-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole. 25. The compound of claim 1 that is 6-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole. 26. The compound of claim 1 that is 6-Carboxy-2-(2,6-dichlorophenyl) -benzoxazole. 27. The compound of claim 1 that is 7-Carboxy-2-(3,5-difluorophenyl) -benzoxazole. 28. The compound of claim 1 that is 7-Carboxy-2-(2,6-difluorophenyl) -benzoxazole. 29. The compound of claim 1 that is 7-Carboxy-2-[(3-trifluoromethyl)phenyl]-benzoxazole. 30. The compound of claim 1 that is 7-Carboxy-2-[(2-trifluoromethyl)phenyl]-benzoxazole. 31. The compound of claim 1 that is 7-Carboxy-2-(3,5-dichlorophenyl) -benzoxazole. 32. The compound of claim 1 that is 7-Carboxy-2-(2,6-dichlorophenyl) -benzoxazole. 33. A pharmaceutical composition comprising a compound of claim 20 and a pharmaceutically acceptable carrier. 34. The pharmaceutical composition of claim 33 that is formulated for single dosage administration. 35. A pharmaceutical composition comprising a compound of claim 26 and a pharmaceutically acceptable carrier. 36. The pharmaceutical composition of claim 35 that is formulated for single dosage administration. 37. A pharmaceutical composition comprising a compound of claim 30 and a pharmaceutically acceptable carrier. 38. The pharmaceutical composition of claim 37 that is formulated for single dosage administration.