IP Library › Granted Patent US 8,637,686
Granted Patent B2
US 8,637,686 · App. 13/097,930 · Granted Jan 28, 2014

Triazole macrocycle systems

Inventor: Huw M. Nash (Concord, MA)
Assignee: Aileron Therapeutics, Inc.
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 8,637,686
App. No.
13/097,930
Granted
Jan 28, 2014
Kind
B2
Abstract

Provided herein are novel alkynyl and azide containing amino acids; kits containing these amino acids; peptides containing these amino acids; peptide macrocycles whose secondary structures are stabilized with linkers containing triazoles synthesized by reacting the side chains of the alkynyl and azide containing amino acids; and methods of making and using the alkynyl and azide containing amino acids, kits, peptides, triazole containing linkers, and peptide macrocycles.

Claims (42)

1. A compound of Formula IIa or IIb:

wherein

R 1 and R 2 are independently alkyl, which is unsubstituted or substituted with halo-;

each Q and T is independently —CH 2 —;

R 7 and R 8 are independently —H;

R 10 and R 11 are independently —H;

R 12 is —H or alkyl;

g and h are each independently-integers and g+h is 3, 4, 5, or 6; and

the compound is enantiomerically enriched.

2. The compound of Formula IIa of claim 1 , wherein R 1 is unsubstituted alkyl.

3. The compound of Formula IIb of claim 1 , wherein R 2 is unsubstituted alkyl.

4. The compound of Formula IIa of claim 1 , wherein R 1 is methyl.

5. The compound of Formula IIb of claim 1 , wherein R 2 is methyl.

6. A kit comprising

(a) at least one compound selected from the group consisting of compounds of Formulas IIa and IIb:

wherein

R 1 is alkyl unsubstituted or substituted with halo-;

R 2 is alkyl unsubstituted or substituted with halo-;

each Q and T is independently —CH 2 —;

R 7 and R 8 are independently —H;

R 10 and R 11 are independently —H;

R 12 is —H or alkyl; and

g and h are each independently-integers and g+h is 3, 4, 5, or 6;

the compound is enantiomerically enriched; and

b) a macrocyclization reagent.

7. The kit of claim 6 , comprising the compound of Formula IIa wherein R 1 is unsubstituted alkyl.

8. The kit of claim 6 , comprising the compound of Formula IIb wherein R 2 is unsubstituted alkyl.

9. The kit of claim 6 , comprising the compound of Formula IIa wherein R 1 is methyl.

10. The kit of claim 6 , comprising the compound of Formula IIb wherein R 2 is methyl.

11. The kit of claim 6 , wherein the kit comprises at least one compound of Formula IIa and at least one compound of Formula IIb.

12. The kit of claim 6 , wherein the macrocyclization reagent is a Cu reagent and in the compound of Formula IIa, R 12 is —H.

13. The kit of claim 6 , wherein the macrocyclization reagent is a Ru reagent.

14. A compound selected from the group consisting of (S)-2-amino-2-methyl-5-hexynoic acid, (R)-2-amino-2-methyl-5-hexynoic acid, (S)-2-amino-2-methyl-6-heptynoic acid, (R)-2-amino-2-methyl-6-heptynoic acid, (S)-2-amino-2-methyl-7-octynoic acid, (R)-2-amino-2-methyl-7-octynoic acid, (S)-2-amino-2-methyl-8-nonynoic acid, (R)-2-amino-2-methyl-8-nonynoic acid, ε-azido-alpha-methyl-L-lysine, ε-azido-alpha-methyl-D-lysine, δ-azido-alpha-methyl-L-ornithine, and δ-azido-alpha-methyl-D-ornithine.

15. A compound selected from the group consisting of N-alpha-Fmoc-(S)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-epsilon-azido-alpha-methyl-L-lysine, N-alpha-Fmoc-epsilon-azido-alpha-methyl-D-lysine, N-alpha-Fmoc-delta-azido-alpha-methyl-L-ornithine, and N-alpha-Fmoc-delta-azido-alpha-methyl-D-ornithine.

16. A kit comprising: a) a compound selected from the group consisting of (S)-2-amino-5-hexynoic acid, (R)-2-amino-5-hexynoic acid, (S)-2-amino-6-heptynoic acid, (R)-2-amino-6-heptynoic acid, (S)-2-amino-7-octynoic acid, (R)-2-amino-7-octynoic acid, (S)-2-amino-8-nonynoic acid, (R)-2-amino-8-nonynoic acid, (S)-2-amino-2-methyl-4-pentynoic acid, (R)-2-amino-2-methyl-4-pentynoic acid, (S)-2-amino-2-methyl-5-hexynoic acid, (R)-2-amino-2-methyl-5-hexynoic acid, (S)-2-amino-2-methyl-6-heptynoic acid, (R)-2-amino-2-methyl-6-heptynoic acid, (S)-2-amino-2-methyl-7-octynoic acid, (R)-2-amino-2-methyl-7-octynoic acid, (S)-2-amino-2-methyl-8-nonynoic acid, (R)-2-amino-2-methyl-8-nonynoic acid, ε-azido-L-lysine, ε-azido-D-lysine, ε-azido-alpha-methyl-L-lysine, ε-azido-alpha-methyl-D-lysine, δ-azido-L-ornithine, δ-azido-D-ornithine, δ-azido-alpha-methyl-L-ornithine, and δ-azido-alpha-methyl-D-ornithine; and

b) a macrocyclization reagent.

17. A kit comprising: a) a compound selected from the group consisting of N-alpha-Fmoc-(S)-2-amino-5-hexynoic acid, N-alpha-Fmoc-(R)-2-amino-5-hexynoic acid, N-alpha-Fmoc-(S)-2-amino-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-7-octynoic acid, N-alpha-Fmoc-(R)-2-amino-7-octynoic acid, N-alpha-Fmoc-(S)-2-amino-8-nonynoic acid, N-alpha-Fmoc-(R)-2-amino-8-nonynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-4-pentynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-5-hexynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-7-octynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-8-nonynoic acid, N-alpha-Fmoc-epsilon-azido-alpha-methyl-L-lysine, N-alpha-Fmoc-epsilon-azido-alpha-methyl-D-lysine, N-alpha-Fmoc-delta-azido-alpha-methyl-L-ornithine, N-alpha-Fmoc-delta-azido-alpha-methyl-D-ornithine, N-alpha-Fmoc-epsilon-azido-L-lysine, and N-alpha-Fmoc-epsilon-azido-D-lysine; and

b) a macrocyclization reagent.

18. A compound selected from the group consisting of N-alpha-Fmoc-(S)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(R)-2-amino-2-methyl-6-heptynoic acid, N-alpha-Fmoc-(S)-2-amino-2-methyl-7-octynoic acid, and N-alpha-Fmoc-(R)-2-amino-2-methyl-7-octynoic acid.

19. A compound selected from the group consisting of N-alpha-Fmoc-epsilon-azido-alpha-methyl-L-lysine, N-alpha-Fmoc-epsilon-azido-alpha-methyl-D-lysine, N-alpha-Fmoc-delta-azido-alpha-methyl-L-ornithine, and N-alpha-Fmoc-delta-azido-alpha-methyl-D-ornithine.

20. The compound of claim 18 , wherein the compound is:

21. The compound of claim 19 , wherein the compound is:

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 22, 2011
From: NASH, HUW M.
To: AILERON THERAPEUTICS, INC.
Reel/Frame 026951/0103 →
Continuity (3)
Division 12037041 · Feb 25, 2008
Provisional Application 60903073 · Feb 23, 2007
Related Publication 20110263815A1 · Oct 27, 2011