Compounds having antiparasitic or anti-infectious activity

1. A method for inhibiting malaria or toxoplasmosis in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula I:

or formula II:

or a pharmaceutically acceptable salt of formula I or formula II, wherein:

R 1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl;

R 2 is methyl, haloalkyl, or heteroaryl;

R 4 is carbonyloxy, or carbonyldioxy;

R 3 is diarly ether; and

R 5 and R 7 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl;

R 6 is H, halogen, alkoxy, alkyl, haloalkyl, aryl, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl; and

R 8 is H, halogen, alkoxy, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl;

provided that in formula I, R 6 is not H or methoxy; and in formula II that if R 4 is carbonyldioxy, then R 7 is not methoxy.

2. The method of claim 1 , wherein R 5 and R 7 of formula I or II are each halogen or haloalkyl.

3. The method of claim 1 , wherein R 4 is carbonyloxy or carbonyldioxy.

4. The method of claim 1 , wherein R 2 of formula I or II is methyl.

5. The method of claim 1 , wherein R 1 is H, alkyl, or cycloalkyl.

6. The method of claim 1 , wherein the compound of formula II has a structure represented by formula III:

wherein R 9 is alkyl, alkenyl, alkyl amino, amido, aminocarbonyl, hydroxyalkyl, alkoxyalkyl or alkyl ether.

7. The method of claim 1 , wherein the compound of formula II has a structure represented by formula IV:

wherein R 9 is alkyl, alkenyl, alkyl amino, amido, aminocarbonyl, hydroxyalkyl, alkoxyalkyl or alkyl ether.

8. The method of claim 1 , wherein the compound is a compound of formula I; and R 3 is trifluoromethoxy-diarylether.

9. The method of claim 8 , wherein R 7 is methoxy.

10. The method of claim 8 , wherein R 6 is halogen.

11. The method of claim 1 , wherein R 3 is

wherein R 13 and R 14 are each individually selected from at least one of alkoxy, halogen-substituted alkoxy, halogenated lower alkyl, alkyl, methylsulfonyl, or halogen; c is 0 to 5; and d is 0 to 5.

12. The method of claim 1 , wherein R 1 is H; R 2 is methyl; R 6 is halogen; R 7 is H or methoxy; and R 5 and R 8 are each H.

13. The method of claim 1 , wherein the compound is a compound, or a pharmaceutically acceptable salt thereof, having a structure of:

14. The method of claim 1 , wherein the compound is a compound, or a pharmaceutically acceptable salt thereof, having a structure of:

15. The method of claim 1 , wherein the compound is a compound of claim 1 , or a pharmaceutically acceptable salt thereof, having a structure of:

16. The method of claim 1 , wherein the method inhibits malaria.

17. The method of claim 16 , wherein the malaria is multidrug-resistant malaria.

18. The method of claim 16 , wherein the malaria is chloroquine-resistant malaria.

19. The method of claim 16 , wherein the compound exhibits equipotency against chloroquine-resistant and multidrug-resistant strains of Plasmodium parasites.

20. The method of claim 16 , wherein the compound is co-administered with at least one other antimalarial agent.

21. The method of claim 1 , wherein the method comprises prophylactic treating the subject against chloroquine-resistant or multidrug-resistant malaria.

22. The method of claim 1 , wherein the method inhibits toxoplasmosis.

23. The method of claim 13 , wherein the method inhibits malaria.

24. The method of claim 14 , wherein the method inhibits malaria.

25. A method for inhibiting malaria or toxoplasmosis in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula XI:

or a pharmaceutically acceptable salt of formula XI, wherein:

R 1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl;

R 2 is H, carboxyl, substituted carboxyl, alkyl, haloalkyl, or heteroaryl;

R 5 , R 7 and R 8 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl;

R 6 is halogen: and

R 3 is an optionally substituted heteroaryl, an optionally substituted alkynyl or an optionally substituted diaryl ether.

26. The method of claim 25 , wherein R 1 is H; R 2 is H or methyl; R 7 is H or methoxy; and R 5 and R 8 are each H.

27. The method of claim 25 , wherein R 3 is

wherein R 13 and R 14 are each individually selected from at least one of alkoxy, halogen-substituted alkoxy, halogenated lower alkyl, alkyl, methylsulfonyl, or halogen; c is 0 to 5; and d is 0 to 5.

28. The method of claim 27 , wherein the method inhibits malaria.

29. A method for inhibiting malaria or toxoplasmosis in a subject comprising administering to the subject a therapeutically effective amount of A compound of formula I:

or a pharmaceutically acceptable salt of formula I, wherein:

R 1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl;

R 2 is methyl, haloalkyl, or heteroaryl;

R 3 is trifluoromethoxy-diarylether; and

R 5 , R 6 , and R 7 and R 8 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl;

provided that in formula I, R 5 and R 7 are not both H or R 6 is not H or methoxy.

30. A method for inhibiting malaria or toxoplasmosis in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula I:

or a pharmaceutically acceptable salt of formula I, wherein:

R 1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl;

R 2 is methyl, haloalkyl, or heteroaryl;

R 3 is

 wherein R 13 and R 14 are each individually selected from at least one of alkoxy, halogen-substituted alkoxy, halogenated lower alkyl, alkyl, methylsulfonyl, or halogen; c is 0 to 5; and d is 0 to 5; and

R 5 , R 6 , and R 7 and R 8 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl;

provided that in formula I, R 5 and R 7 are not both H or R 6 is not H or methoxy.

31. A method for inhibiting malaria or toxoplasmosis in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula I:

or a pharmaceutically acceptable salt of formula I, wherein:

R 1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl;

R 2 is methyl, haloalkyl, or heteroaryl;

R 3 is trifluoromethoxy-diarylether; and

R 5 and R 7 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl;

R 6 is H, halogen, alkoxy, alkyl, haloalkyl, aryl, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl; and

R 8 is H, halogen, alkoxy, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO 2 R 10 , wherein R 10 is H, alkyl, amino or haloalkyl;

provided that in formula I, R 6 is not H or methoxy.