Human TLR8-selective agonists

1. A compound represented by Formula (II):

or a salt thereof, wherein:

R 1 is selected from the group consisting of

R 2 , R 3 , R 4 , and R 5 are independently selected from the group consisting of: H, halogen, —OR 10 , —N(R 10 ) 2 , —SR 10 , —CN, —NO 2 , —OC(O)R 10 , —C(O)R 10 , —C(O)OR 10 , —C(O)N(R 10 ) 2 , —S(O) 2 R 10 , —S(O) 2 OR 10 , optionally substituted C 1-20 alkyl, optionally substituted C 2-20 alkenyl, optionally substituted C 2-20 alkynyl, optionally substituted C 3-20 carbocycle, and optionally substituted 3- to 20-membered heterocycle;

R 6 is selected from the group consisting of —OR 11 , —N(R 11 ) 2 , —SR 11 , optionally substituted C 1-20 alkyl, optionally substituted C 2-20 alkenyl, and optionally substituted C 2-20 alkynyl;

R 7 and R 8 are each independently H;

R 10 is independently selected at each occurrence from the group consisting of H, optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-12 carbocycle and optionally substituted 3- to 12-membered heterocycle; and

R 11 is independently selected at each occurrence from the group consisting of optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, and optionally substituted C 2-10 alkynyl.

2. The compound or salt of claim 1 , wherein R 1 is selected from:

3. The compound or salt of claim 1 , wherein R 3 is selected from:

4. The compound or salt of claim 1 , wherein R 2 , R 4 , and R 5 are independently selected from the group consisting of: H, halogen, —OR 10 , —N(R 10 ) 2 , —CN, —NO 2 , —OC(O)R 10 , —C(O)R 10 , —C(O)OR 10 , —C(O)N(R 10 ) 2 , —S(O) 2 R 10 , —S(O) 2 OR 10 , and substituted C 1-20 alkyl.

5. The compound or salt of claim 1 , wherein R 10 is selected from the group consisting of:

optionally substituted C 1-20 alkyl, optionally substituted C 2-20 alkenyl, optionally substituted C 2-20 alkynyl, wherein the C 1-20 alkyl, C 2-20 alkenyl, and C 2-20 alkynyl optional substituents are one or more substituents independently selected from the group consisting of: halogen, —CN, —NO 2 , OR 50 , —SR 50 , N(R 50 ) 2 , —NR 50 C(N(R 50 ))N(R 50 ) 2 , —OC(O)R 50 , —C(O)R 50 , —C(O)OR 50 , —C(O)N(R 50 ) 2 , —S(O) 2 R 50 , —S(O) 2 OR 50 , C 3-12 carbocycle, and 3- to 12-membered heterocycle, wherein the C 3-12 carbocycle and 3- to 12-membered heterocycle are optionally substituted with one or more substituents selected from the group consisting of halogen, —CN, —NO 2 , —OR 50 , —SR 50 , —N(R 50 ) 2 , C 1-10 alkyl, C 1-10 haloalkyl, —C 1-10 alkyl —N(R 50 ) 2 , —C 1-10 alkyl-OR 50 , and —C 1-10 alkyl-C(O)N(R 50 ) 2 ; and

optionally substituted C 3-20 carbocycle and optionally substituted 3- to 20-membered heterocycle, wherein the C 3-20 carbocycle and 3- to 20-membered heterocycle optional substituents are one or more substituents independently selected from the group consisting of: halogen, —CN, —NO 2 , —OR 50 , —SR 50 , —N(R 50 ) 2 , C 1-10 alkyl, C 1-10 haloalkyl, —C 1-10 )alkyl-N(R 50 ) 2 , —C 1-10 alkyl-OR 50 , and —C 1-10 alkyl-C(O)N(R 50 ) 2 ; and

wherein R 50 at each occurrence is independently selected from the group consisting of hydrogen, C 1-10 alkyl, and C 1-10 haloalkyl.

6. The compound or salt of claim 1 , wherein R 6 is selected from the group consisting of optionally substituted C 1-20 alkyl, optionally substituted C 2-20 alkenyl, and optionally substituted C 2-20 alkynyl.

7. The compound or salt of claim 1 represented by:

or a salt thereof.

8. A pharmaceutical composition comprising a compound or salt of claim 1 , and a pharmaceutically acceptable excipient, optionally wherein the composition further comprises a vaccine.

9. A method for modulating activity of a human toll-like receptor, comprising administering to a subject in need thereof a compound of claim 1 or a salt thereof.

10. The method of claim 9 , wherein modulating the activity of the human toll-like receptor comprises agonizing the human toll-like receptor.

11. The method of claim 9 , wherein the human toll-like receptor comprises hTLR8.

12. The method of claim 9 , wherein the method further comprises administering a vaccine to the subject before, in conjunction with, or after administration of the compound or salt thereof.

13. A method of increasing an immune response to an antigen or vaccine, wherein the method comprises administering to a subject in need thereof a compound of claim 1 or a salt thereof.

14. The method of claim 13 , wherein R 1 is selected from:

15. The method of claim 9 , wherein R 3 is selected from:

16. The method of claim 9 , wherein the compound is represented by:

or a salt thereof.