IP Library › Granted Patent US 10,526,359

Granted Patent B2

US 10,526,359 · App. 15/822,616 · Granted Jan 7, 2020

Thiosaccharide mucolytic agents

Inventors: Stefan Oscarson (Blackrock, IE); John Vincent Fahy (San Francisco, CA); Shaopeng Yuan (San Francisco, CA); Stephen Carrington (Roundwood, IE)

Assignees: The Regents of the University of California; University College Dublin

C07H15/04 A61K31/70 A61K31/702 A61K31/7016 A61K31/7028 C07D309/10 C07H5/04 C07H13/04

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Quick Facts

Patent No.: US 10,526,359
App. No.: 15/822,616
Granted: Jan 7, 2020
Kind: B2

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Abstract

There are provided, inter alia, methods for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, the methods including administering to the subject an effective amount of a thiosaccharide mucolytic agent, and compounds and pharmaceutical compositions useful for the methods.

Claims (224)

1. A method for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, said method comprising administering to said subject in need thereof an effective amount of a thiol saccharide mucolytic agent, wherein said thiol saccharide mucolytic agent has the formula:

wherein,

R 1 is —SH, —OR 1A or —NR 1B , wherein

R 1A is H, substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 1B is —C(O)R 1C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 1C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2 is —SH, —OR 2A or NR 2B , wherein

R 2A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2B is —C(O)R 2C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 2C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3 is —SH, —OR 3A or —NR 3B , wherein

R 3A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3B is —C(O)R 3c , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 3C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5 is H, —SH, —SAc, —OR 5A or —NR 5B , wherein

R 5A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5B is —C(O)R 5C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 5C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7 is —SH, —OR 7A or —NR 7B , wherein

R 7A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7B is —C(O)R 7C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 7C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8 is —SH, —OR 8A or —NR 8B , wherein

R 8A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8B is —C(O)R 8C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 8C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9 is —SH, —OR 9A or —NR 9B , wherein

R 9A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9B is —C(O)R 9C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 9C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 10 is H, —SH, —SAc, —OR 10A or —NR 10B , wherein

R 10A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 10B is —C(O)R 10C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 10C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl,

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein said method comprises decreasing mucus viscoelasticity in said subject.

3. The method of claim 1 , wherein said thiosaccharide mucolytic agent comprises D-glucopyranose, D-galactopyranose, D-mannopyranose, D-glucopyranoside, D-galactopyranoside, or D-mannopyranoside moieties.

4. The method of claim 1 , wherein said thiosaccharide mucolytic agent comprises D-galactopyranose.

5. The method of claim 1 , wherein

R 1 is —OR 1A ; and

R 2 , R 3 , R 5 , R 7 , R 8 , and R 9 are —OH; and

R 10 is —SH or —OR 10A .

6. The method of claim 5 , wherein

R 1A is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl.

7. The method of claim 6 , wherein

R 1A is unsubstituted C 1 -C 10 thiol-alkyl; and

R 1 is —OH.

8. The method of claim 7 , wherein R 1A is thioethyl.

9. The method of claim 5 , wherein

R 1A is H; and

R 10 is —SH.

10. The method of claim 1 , wherein

R 1A is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2 , R 3 , R 5 , R 7 , R 8 , and R 9 are —OH; and

R 10 is —SH.

11. The method of claim 10 , wherein R 1A is unsubstituted C 1 -C 10 thiol-alkyl.

12. The method of claim 11 , wherein R1A is thioethyl.

13. The method of claim 1 , wherein

R 1 , R 3 , R 5 , R 8 , R 9 , and R 10 are —OH;

R 2 is —OH or —NR 2B ;

R 2C is substituted or unsubstituted C 1 -C 10 thiol-alkyl;

R 7 is —OH or —NR 7B ; and R 7C is substituted or unsubstituted C 1 -C 10 thiol-alkyl.

14. The method of claim 1 , wherein

R 1 is —OR 1A ;

R 1A is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3 , R 5 , R 8 , R 9 , and R 10 are —OH;

R 2 is —OH or —NR 2B ;

R 2C is substituted or unsubstituted C 1 -C 10 alkyl;

R 7 is —OH or —NR 7B ; and

R 7C is substituted or unsubstituted C 1 -C 10 alkyl.

15. The method of claim 14 , wherein

R 2 is —NHAc; and

R 7 is —NHAc.

16. A thiol saccharide compound with structure of Formula (III):

wherein,

R 1 is —OR 1A or —NR 1B , wherein

R 1A is H, substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 1B is —C(O)R 1C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 1C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2 is —SH, —OR 2A or —NR 2B , wherein

R 2A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2B is —C(O)R 2C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 2C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3 is —SH, —OR 3A or —NR 3B , wherein

R 3A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3B is —C(O)R 3C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 3C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5 is H, —SH, —SAc, —OR 5A or —NR 5B , wherein

R 5A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5B is —C(O)R 5C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 5C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7 is —SH, —OR 7A or —NR 7B , wherein

R 7A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7B is —C(O)R 7C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 7C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8 is —SH, —OR 8A or —NR 8B , wherein

R 8A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8B is —C(O)R 8C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 8C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9 is —SH, —OR 9A or —NR 9B , wherein

R 9A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9B is —C(O)R 9C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 9C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 10 is H, —SAc, —OR 10A or —NR 10B , wherein

R 10A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 10B is —C(O)R 10C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 10C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl.

17. The compound of claim 16 , having the structure

18. The compound of claim 16 , having the structure

19. A pulmonary pharmaceutical composition comprising a pulmonary pharmaceutical carrier and a thiol saccharide mucolytic agent, wherein said thiol saccharide mucolytic agent has the formula:

wherein,

R 1 is —SH, —OR 1A or —NR 1B , wherein

R 1A is H, substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 1B is —C(O)R 1C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 1C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2 is —SH, —OR 2A or NR 2B , wherein

R 2A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2B is —C(O)R 2C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 2C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3 is —SH, —OR 3A or —NR 3B , wherein

R 3A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3B is —C(O)R 3C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 3C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5 is H, —SH, —SAc, —OR 5A or —NR 5B , wherein

R 5A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5B is —C(O)R 5C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 5C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7 is —SH, —OR 7A or —NR 7B , wherein

R 7A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7B is —C(O)R 7C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 7C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8 is —SH, —OR 8A or —NR 8B , wherein

R 8A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8B is —C(O)R 8C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 8C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9 is —SH, —OR 9A or —NR 9B , wherein

R 9A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9B is —C(O)R 9C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 9C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 10 is H, —SH, —SAc, —OR 10A or —NR 10B , wherein

R 10A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 10B is —C(O)R 10C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 10C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl,

or a pharmaceutically acceptable salt thereof.

20. The method of claim 1 , wherein R1 is —SH.

21. The method of claim 1 , wherein R5 is —SH.

22. The method of claim 1 , wherein R7 is —SH.

23. The method of claim 1 , wherein R10 is —SH.

24. The composition of claim 19 , wherein

R 1 is —OR 1A ; and

R 2 , R 3 , R 5 , R 7 , R 8 , and R 9 are —OH; and

R 10 is —SH or —OR 10A .

25. The composition of claim 24 , wherein

R 1A is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl.

26. The composition of claim 25 , wherein

R 1A is unsubstituted C 1 -C 10 thiol-alkyl; and

R 10 is —OH.

27. The composition of claim 26 , wherein R1A is thioethyl.

28. The composition of claim 24 , wherein

R 1A is H; and

R 10 is —SH.

29. The composition of claim 19 , wherein

R 1A is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2 , R 3 , R 5 , R 7 , R 8 , and R 9 are —OH; and

R 10 is —SH.

30. The composition of claim 29 , wherein R1A is unsubstituted C1-C10 thiol-alkyl.

31. The composition of claim 30 , wherein R1A is thioethyl.

32. The composition of claim 19 , wherein

R 1 , R 3 , R 5 , R 8 , R 9 , and R 10 are —OH;

R 2 is —OH or —NR 2B ;

R 2C is substituted or unsubstituted C 1 -C 10 thiol-alkyl;

R 7 is —OH or —NR 7B ; and R 7C is substituted or unsubstituted C 1 -C 10 thiol-alkyl.

33. The composition of claim 19 , wherein

R 1 is —OR 1A ;

R 1A is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3 , R 5 , R 8 , R 9 , and R 10 are —OH;

R 2 is —OH or —NR 2B ;

R 2C is substituted or unsubstituted C 1 -C 10 alkyl;

R 7 is —OH or —NR 7B ; and

R 7C is substituted or unsubstituted C 1 -C 10 alkyl.

34. The composition of claim 31 , wherein

R 2 is —NHAc; and

R 7 is —NHAc.

35. The composition of claim 19 , wherein R1 is —SH.

36. The composition of claim 19 , wherein R5 is —SH.

37. The composition of claim 19 , wherein R7 is —SH.

38. The composition of claim 19 , wherein R10 is —SH.

39. The method of claim 1 , wherein said thiol saccharide mucolytic agent has the structure:

40. The composition of claim 19 , wherein said thiol saccharide mucolytic agent has the structure:

41. A thiol saccharide compound with structure of Formula (III):

wherein,

R 1 is —SH, —OR 1A or —NR 1B , wherein

R 1A is H, substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 1B is —C(O)R 1C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 1C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2 is —SH, —OR 2A or —NR 2B , wherein

R 2A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 2B is —C(O)R 2C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 2C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3 is —SH, —OR 3A or —NR 3B , wherein

R 3A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 3B is —C(O)R 3C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 3C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5 is H, —SH, —SAc, —OR 5A or —NR 5B , wherein

R 5A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 5B is —C(O)R 5C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 5C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7 is —SH, —OR 7A or —NR 7B , wherein

R 7A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 7B is —C(O)R 7C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 7C is substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8 is —SH, —OR 8A or —NR 8B , wherein

R 8A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 8B is —C(O)R 8C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 8C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9 is —SH, —OR 9A or —NR 9B , wherein

R 9A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 9B is —C(O)R 9C , substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 9C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 10 is H, —SH, —SAc, —OR 10A or —NR 10B , wherein

R 10A is H, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

R 10B is —C(O)Roc, substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl; and

R 10C is substituted or unsubstituted C 1 -C 10 thiol-alkyl or substituted or unsubstituted 2 to 10 membered thiol-heteroalkyl;

provided, however, that at least one of R 3A , R 5A , R 7A , R 8A , and R 9A is not H.

Assignments (3)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 29, 2019

From: FAHY, JOHN VINCENT; YUAN, SHAOPENG

To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Reel/Frame 049025/0539 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 29, 2019

From: CARRINGTON, STEPHEN; OSCARSON, STEFAN

To: UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Reel/Frame 049025/0587 →

CONFIRMATORY LICENSE Recorded Feb 23, 2018

From: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT

Reel/Frame 045430/0355 →

Continuity (4)

Division 14847439 · Sep 8, 2015

Continuation PCTUS2014028656 · Mar 14, 2014

Provisional Application 61784856 · Mar 14, 2013

Related Publication 20180111955A1 · Apr 26, 2018

Cited By (1)

US 12,187,762