Peptidomimetic macrocycles

• US 9,175,047 B2
• Filed: 01/14/2010
• Issued: 11/03/2015
• Est. Priority Date: 01/14/2009
• Status: Active Grant

• Current Assignee: Wilson Sonsini Goodrich & Rosati
• Original Assignee: Aileron Therapeutics Inc.
• Inventors: Nash, Huw M., Annis, David Allen
• Primary Examiner(s): Ha, Julie
• Application Number:
  US13/129,118
• Publication Number:
  US 20120040889A1
• Time in Patent Office: 2,119 Days
• Field of Search: 514/3.7, 530/323
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C07K 7/54 with at least one abnormal peptide link in the ring
• CPC Class Codes: C07K 7/56 the cyclisation not occurring through 2,4-diamino-butanoic acid
• CPC Class Codes: C07K 7/64 Cyclic peptides containing only normal peptide links
• CPC Class Codes: C12N 2760/16022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Peptidomimetic macrocycles and methods of using such macrocycles for the treatment of viral disease are described.

Claims

1. A peptidomimetic macrocycle-comprising a crosslinker linking the α

-positions of at least two amino acids, and an amino acid sequence that is at least 80% identical to the amino acid sequence NleDVN$TLL$LKVAibAQ (SEQ ID NO;

     113) and, wherein the peptidomimetic macrocycle has a structure of Formula (I);

2. The peptidomimetic macrocycle of claim 1, wherein the amino acid sequence of the peptidomimetic macrocycle is at least about 90% identical to the amino acids sequence NleDVN$TLL$LKVAibAQ (SEQ ID NO:

113).

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

4. The peptidomimetic macrocycle of claim 1, wherein the peptidomimetic macrocycle comprises a 3₁₀ helix.

5. The peptidomimetic macrocycle of claim 1, wherein the peptidomimetic macrocycle comprises an α

,α

-disubstituted amino acid.

6. The peptidomimetic macrocycle of claim 1, wherein x+y+z=6.

7. The peptidomimetic macrocycle of claim 1, wherein the peptidomimetic macrocycle comprises an alpha helix.

8. The peptidomimetic macrocycle of claim 1, wherein R₁ is alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-.

9. The peptidomimetic macrocycle of claim 1, wherein R₁ and R₂ are independently alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-.