Imidazopyrimidine compounds and uses thereof
The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds described herein are used as enhancers and/or modifiers of an immune response (e.g., innate and/or adaptive immune response), and are useful in treating and/or preventing a disease, as adjuvants in a vaccine for the disease, (e.g., proliferative disease, inflammatory disease, autoimmune disease, infectious disease, or chronic disease), or as stand alone anti-infective or immune response modifying agents. Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.
1. A compound 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 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 1, 2, or 3; and
b is 0, 1, 2, or 3.
2. The compound of claim 1 , 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.
3. The compound of claim 1 , wherein R 1 is halogen or substituted or unsubstituted C 1-6 alkyl.
4. The compound of claim 1 , wherein R 1A is of the formula:
5. The compound of claim 2 , wherein at least one instance of R 2 is substituted or unsubstituted C 1-6 alkyl.
6. The compound of claim 5 , wherein at least one instance of R 2 is Me or Et.
7. The compound of claim 1 , wherein R A is halogen, substituted or unsubstituted C 1-6 alkyl, or —O (substituted or unsubstituted C 1-6 alkyl).
8. The compound of claim 7 , wherein R A is —F, Me, or —OMe.
9. The compound of claim 1 , wherein a is 1.
10. The compound of claim 1 , wherein b is 0.
11. The compound of claim 2 , wherein c is 0.
12. The compound of claim 2 , wherein c is 1.
13. The compound of claim 2 , wherein R C is halogen or substituted or unsubstituted C 1-6 alkyl.
14. The compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.
16. The compound of claim 1 , wherein R 1A is of formula:
wherein:
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 .
17. The compound of claim 2 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 2 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 2 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.