Immune system modulators

1. A method of treating a condition selected from the group consisting of an autoimmune disease, inflammation, allergy, asthma, graft rejection, graft-versus host disease (GvHD), and sepsis, in a mammalian species in need thereof, comprising administering to the mammalian species a therapeutically effective amount 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;

wherein the autoimmune disease and inflammation are each characterized by unwanted immune activity.

2. The method of claim 1 , wherein the autoimmune disease is selected from the group consisting of cutaneous and systemic lupus erythematosus, insulin-dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, atherosclerosis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis, autoimmune hemolytic anemia, Behget's syndrome, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, idiopathic thrombocytopenia, io myasthenia gravis, pernicious anemia, polyarteritis nodosa, polymyositis/dermatomyositis, primary biliary sclerosis, sarcoidosis, sclerosing cholangitis, Sjogren's syndrome, systemic sclerosis (scleroderma and CREST syndrome), Takayasu's arteritis, temporal arteritis, and Wegener's granulomatosis.

3. 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.

4. 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 .

5. 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 .

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

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

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

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

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

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

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

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

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

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

16. 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.

17. 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 .

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

19. The method of claim 17 , wherein R 11 is H.

20. The method of claim 17 , wherein NR 3 R 4 , NR 1 R 2 , and NR b R c are each independently

21. The method of claim 17 , wherein q is 0.

22. The method of claim 17 , wherein R 5 is halogen.

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

24. The method of claim 17 , wherein R b is H.

25. The method of claim 17 , wherein p is 2.

26. The method of claim 17 , 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 18 .

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

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

29. The method of claim 27 , wherein NR 1 R 2 is NHBu.

30. The method of claim 1 , wherein the autoimmune disease and inflammation are each characterized by TLR-mediated immunostimulation.