Use of imidazopyrimidine for modulating human immune response

Patent metadata

Field	Value
Publication number	US-2020282048-A1
Application number	US-201816763847-A
Country	US
Kind code	A1
Filing date	Nov 14, 2018
Priority date	Nov 14, 2017
Publication date	Sep 10, 2020
Grant date	—

Abstract

Provided herein are imidazopyrimidine compounds for use in enhancing human immune response and/or as adjuvants in vaccines.

First claim

What is claimed is:

1 . A composition comprising an antigen and an imidazopyrimidine compound.

2 . The composition of claim 1 , wherein the antigen comprises a protein or polypeptide.

3 . The composition of claim 1 or claim 2 , wherein the antigen comprises a nucleic acid encoding a protein or a polypeptide.

4 . The composition of claim 3 , wherein the nucleic acid is DNA or RNA.

5 . The composition of any one of claims 1 - 4 , wherein the antigen is from a microbial pathogen.

6 . The composition of claim 5 , wherein the microbial pathogen is a bacterium, mycobacterium, fungus, virus, parasite, or prion.

7 . The composition of claim 6 , wherein the bacterium is Bacillus anthracis, Bordetella pertussis, Corynebacterium diphtheriae, Clostridium tetani, Haemophilus influenzae type b, pneumococcus, Staphylococci spp., Mycobacterium tuberculosis, Neiserria meningitidis, Salmonella typhi, Vibrio cholerae , or Yersinia pestis.

8 . The composition of claim 6 , wherein the virus is adenovirus, enterovirus such as poliomyelitis, Ebola virus, herpes viruses such as herpes simplex virus, cytomegalovirus and varicella-zoster, measles, mumps, rubella, hepatitis A virus, hepatitis B virus, hepatitis C virus, human papilloma virus, Influenza virus, rabies, Japanese encephalitis, rotavirus, human immunodeficiency virus (HIV), respiratory syncytial virus (RSV), smallpox, yellow fever, or Zika Virus.

9 . The composition of claim 6 , wherein the parasite is Plasmodium spp., Leishmania , or a helminth.

10 . The composition of claim 6 , wherein the fungus is Candida spp., Aspergillus spp., Cryptococcus spp., Mucormycete, Blastomyces dermatitidis, Histoplasma capsulatum , or Sporothrix schenckii.

11 . The composition of any one of claims 1 - 4 , wherein the antigen is a cancer-specific antigen.

12 . The composition of claim 11 , wherein the antigen is a heteroclitic epitope or a cryptic epitope derived from the cancer-specific antigen.

13 . The composition of claim 11 , wherein the cancer-specific antigen is a neoantigen.

14 . The composition of claim 1 , wherein the antigen comprises a lipopolysaccharide (LPS).

15 . The composition of any one of claims 1 - 14 , wherein the imidazopyrimidine compound is of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R 1A is substituted or unsubstituted phenyl or substituted or unsubstituted benzyl, or substituted or unsubstituted 6-membered heteroaryl;
R 1 is hydrogen, halogen, substituted or unsubstituted C 1-6 alkyl, —OR a , or —N(R a1 ) 2 ;
each instance of R A is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR a , —N(R a1 ) 2 , —SR a , —CN, —C(═O)R a , —C(═O)OR a , —C(═O)N(R a1 ) 2 , or —NO 2 ;
each instance of R B is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR a , —N(R a1 ) 2 , —SR a , —CN, —C(═O)R a , —C(═O)OR a , —C(═O)N(R a1 ) 2 , or —NO 2 ;
each instance of R a is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;
each instance of R a1 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, or two instances of R a1 are joined to form a substituted or unsubstituted, heterocyclic ring, or substituted or unsubstituted, heteroaryl ring;
a is 0, 1, 2, or 3; and
b is 0, 1, 2, or 3.

16 . The composition of claim 15 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof, wherein:
each instance of R 2 is independently hydrogen, halogen, substituted or unsubstituted C 1-6 alkyl, —OR a , or —N(R a1 ) 2 ;
each instance of R C is independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR a , —N(R a1 ) 2 , —SR a , —CN, —C(═O)R a , —C(═O)OR a , —C(═O)N(R a1 ) 2 , or —NO 2 ; and
c is 0, 1, 2, 3, 4, or 5.

17 . The composition of any one of claims 15 or 16 , wherein R 1 is halogen or substituted or unsubstituted C 1-6 alkyl.

18 . The composition of any one of claims 1 or 2 , wherein R 1A is of the formula:

19 . The composition of claim 16 , wherein at least one instance of R 2 is substituted or unsubstituted C 1-6 alkyl.

20 . The composition of claim 19 , wherein at least one instance of R 2 is Me or Et.

21 . The composition of any one of claims 15 or 16 , wherein R A is halogen, substituted or unsubstituted C 1-6 alkyl, or —O(substituted or unsubstituted C 1-6 alkyl).

22 . The composition of claim 21 , wherein R A is —F, Me, or —OMe.

23 . The composition of any one of claims 15 - 22 , wherein a is 1.

24 . The composition of any one of claims 15 - 22 , wherein a is 0.

25 . The composition of any one of claims 15 - 24 , wherein b is 0.

26 . The composition of any one of claims 15 - 25 , wherein c is 0.

27 . The composition of any one of claims 15 - 25 , wherein c is 1.

28 . The composition of any one of claims 1 - 25 or 27 , wherein R C is halogen or substituted or unsubstituted C 1-6 alkyl.

29 . The composition of any one of claims 15 - 28 , wherein the compound is of the formula:

30 . The composition of any one of claims 15 - 28 , wherein the compound is of the formula:

Assignees

• Childrens Medical Center
• Dana Farber Cancer Inst Inc

Inventors

• Levy Ofer
• Dowling David J
• Borriello Francesco
• Scott David A
• Brightman Spencer E
• Feru Frederic

Classifications

• A61P37/02

  Immunomodulators · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D403/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title