Peptidomimetic macrocycles

Patent metadata

Field	Value
Publication number	US-10022422-B2
Application number	US-201615093373-A
Country	US
Kind code	B2
Filing date	Apr 7, 2016
Priority date	Jan 14, 2009
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

Novel peptidomimetic macrocycles and methods of using such macrocycles for the treatment of viral diseases are described.

First claim

What is claimed is:

1. A composition comprising:
a) a peptidomimetic macrocycle comprising an amino acid sequence wherein two amino acids in the amino acid sequence are cross-linked by a crosslinker, wherein the crosslinker comprises a 1, 5-disubstituted triazole and does not comprise a 1,4-disubstituted triazole;
b) a Cu(I) species; and
c) a Ru(II) species.

2. The composition of claim 1 , wherein the peptidomimetic macrocycle comprises a helix.

3. The composition of claim 2 , wherein the helix is an alpha helix.

4. The composition of claim 1 , wherein the peptidomimetic macrocycle comprises a beta turn.

5. The composition of claim 1 , wherein the peptidomimetic macrocycle comprises an α,α-disubstituted amino acid.

6. The composition of claim 1 , wherein the peptidomimetic macrocycle comprises more than one stabilized secondary structure.

7. The composition of claim 1 , wherein the cross-linked amino acids are at position i and i+3 of the peptidomimetic macrocycle.

8. The composition of claim 1 , wherein the crosslinker spans one turn of a secondary structure of the peptidomimetic macrocycle.

9. The composition of claim 1 , wherein the crosslinker spans two turns of a secondary structure of the peptidomimetic macrocycle.

10. The composition of claim 1 , wherein the peptidomimetic macrocycle comprises more than two cross-linked amino acids.

11. The composition of claim 1 , wherein the 1, 5-disubstituted triazole has a formula

and the 1, 4-disubstituted triazole has a formula

wherein L 1 and L 2 are independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, cycloarylene, heterocycloarylene, or [—R 4 —K—R 4 -]n, each being optionally substituted with R 5 ;
each R 4 is alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene;
each K is O, S, SO, SO 2 , CO, CO 2 , or CONR 3 ;
each R 5 is independently halogen, alkyl, —OR 6 , —N(R 6 ) 2 , —SR 6 , —SOR 6 , —SO 2 R 6 , —CO 2 R 6 , a fluorescent moiety, a radioisotope or a therapeutic agent;
each R 6 is independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkylalkyl, heterocycloalkyl, a fluorescent moiety, a radioisotope or a therapeutic agent; and
n is an integer from 1 to 5.

12. The composition of claim 11 , wherein each L 1 and L 2 is independently an alkylene.

Assignees

• Aileron Therapeutics Inc
• Alleron Therapeutics Inc

Inventors

• Nash Huw M
• Annis David Allen

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C12N2760/16022

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C07K14/005

  from viruses · CPC title

• A61K38/10 Primary

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title