Immune system modulators

1. A method of inhibiting TLR-mediated immunostimulation in a mammalian species in need thereof, comprising administering to the mammalian species a therapeutically effective amount of at least one compound of at least one compound of Formula I or a pharmaceutically acceptable salt thereof,

wherein

X is absent or is an optionally substituted alkyl, cycloalkyl, aryl, alkylaryl, or heterocycle;

Q is H, (CH 2 ) q NR 1 R 2 , NR 1 (CH 2 ) p NR b R c , OR 1 , or SR 1 , in which q is 0 or 1;

R 1 and R 2 are each independently hydrogen, alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocycle, alkylheterocycle, or R 1 and R 2 , when connected to N, together with the nitrogen atom to which they are bonded form a heterocycle, which may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of optionally substituted (C 1 -C 4 )alkyl, phenyl, benzyl, C(═O)R 12 , (CH 2 ) p OR a , and (CH 2 ) p NR b R c ;

R 7 is NR 3 R 4 ;

R 3 and R 4 are each independently hydrogen, alkyl, cycloalkyl, alkenyl, or alkylaryl, or R 3 and R 4 together with the nitrogen atom to which they are bonded form a heterocycle;

Y is oxygen, sulfur, or NR 11 , where R 11 is hydrogen, alkyl, cycloalkyl, alkenyl, or aryl group;

R 12 is alkyl, aryl, or heterocycle;

L is alkyl or alkenyl containing from 2 to 10 carbon atoms;

R 5 is hydrogen, halogen, cyano, OR a , SR a , S(═O)R a , S(═O) 2 R a , NR b R c , S(═O) 2 NR b R c , C(═O)OR a , C(═O)R a , C(═O)NR b R c , OC(═O)R a , OC(═O)NR b R c , NR b C(═O)OR a , NR b C(═O)R a , -or NR b (CH 2 ) p NR b R c ;

R 6 is halogen, cyano, aryl, SR a , S(═O)R a , S(═O) 2 R a , NR b R c , S(═O) 2 NR b R c , C(═O)OR a , C(═O)R a , C(═O)NR b R c , OC(═O)R a , OC(═O)NR b R c , NR b C(═O)OR a , NR b C(═O)R a , alkaryl, alkylheterocyclic, or NR b (CH 2 ) p NR b R c ;

each occurrence of p is independently 2-4;

each occurrence of R a is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; and

each occurrence of R b and R c is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said R b and R c together with the nitrogen atom to which they are bonded optionally form a heterocycle comprising 1-4 heteroatoms, wherein the heterocycle is optionally substituted by (C 1 -C 4 )alkyl;

provided that when R 5 and R 6 are H or methyl, then Q is not H.

2. The method of claim 1 , wherein

X is absent or is an aryl, or heterocycle; and

Q is (CH 2 ) q NR 1 R 2 , NR 1 (CH 2 ) p NR b R c , OR 1 , or SR 1 , in which q is 0 or 1 and p is 2-4.

3. The method of claim 1 , wherein

X is absent or is aryl, or heterocycle;

Q is (CH 2 ) q NR 1 R 2 , NR 1 (CH 2 ) p NR b R c , OR 1 , or SR 1 , in which q is 0 or 1 and p is 2-4; R 1 and R 2 are each independently hydrogen, alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocycle, alkylheterocycle, or R 1 and R 2 together with the nitrogen atom to which they are bonded form a heterocycle, which may be optionally substituted by from one to four groups which may be the same or different selected from (C 1 -C 4 )alkyl;

R 5 is hydrogen, halogen, cyano or NR b (CH 2 ) p NR b R c ; and

R 6 is halogen, cyano or NR b (CH 2 ) p NR b R c .

4. The method of claim 1 , wherein X is absent, alkyl or cycloalkyl and Q is (CH 2 ) q NR 1 R 2 , NR 1 (CH 2 ) p NR b R c , or SR 1 .

5. The method of claim 1 , wherein R 6 is alkaryl, alkylheterocyclic, or NR b (CH 2 ) p NR b R c .

6. The method of claim 1 , wherein Q is NR 1 (CH 2 ) p NR b R c .

7. The method of claim 1 , wherein X is optionally substituted alkyl, cycloalkyl, aryl, or heterocycle.

8. The method of claim 1 , wherein X is optionally substituted heterocycle.

9. The method of claim 7 , wherein X is halogen-substituted alkyl, halogen-substituted cycloalkyl, halogen-substituted aryl, or halogen-substituted heterocycle.

10. The method of claim 1 , wherein X is optionally substituted piperazine.

11. The method of claim 1 , wherein Y is oxygen or sulfur.

12. The method of claim 1 , wherein Y is NR 11 .

13. The method of claim 1 , wherein R 11 is H.

14. The method of claim 1 , wherein L is —CH 2 CH 2 —.

15. The method of claim 1 , wherein NR 1 R 2 , NR 3 R 4 , and NR b R c are each independently a heterocycle selected from the group consisting of:

in which R d is H, Me, CF 3 , Et, n-Pr, i-Pr, n-Bu, i-Bu, t-Bu, CH 2 CMe 3 , Ph, CH 2 Ph, C(═O)R 12 , (CH 2 ) p′ OR a′ , (CH 2 ) p′ C(═O)OR a′ , optionally substituted pyridine, C(═O)NR b′ R c′ , and (CH 2 ) p′ NR b′ R c′ , wherein R 12 is alkyl, phenyl, or heterocycle; R a′ , R b′ and R c′ are each independently hydrogen, or (C 1 -C 4 )alkyl, or R b′ and R c′ , together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of alkyl, phenyl and benzyl; and p′ is 0-4.

16. The method of claim 1 , wherein the compound has the structure of:

wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 11 , p, R b and R c are as described in claim 1 .

17. The method of claim 16 , wherein L is —CH 2 CH 2 —.

18. The method of claim 16 , wherein R 11 is H.

19. The method of claim 16 , wherein NR 3 R 4 , NR 1 R 2 , and NR b R c are each independently

20. The method of claim 16 , wherein q is 0.

21. The method of claim 16 , wherein R 5 is halogen.

22. The method of claim 21 , wherein R 5 is Cl.

23. The method of claim 16 , wherein R b is H.

24. The method of claim 16 , wherein p is 2.

25. The method of claim 16 , wherein the compound has the structure of:

wherein R 1 , R 2 , R 3 , R 4 , R 5 , R b and R c are as described in claim 1 .

26. The method of claim 25 , wherein NR 3 R 4 , NR 1 R 2 , and NR b R c are each independently

27. The method of claim 25 , wherein R 5 is Cl.

28. The method of claim 25 , wherein NR 1 R 2 is NHBu.