Lp-PLA2 inhibitors

1. A compound having the structure of Formula (I), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

R 1 is selected from the group consisting of —N(R 10 )R 11 , —OH, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 2 is selected from the group consisting of hydrogen, halogen, —N(R 12 )R 13 , —CF 3 , C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 3 is hydrogen or C 1 -C 3 alkyl;

R 4 and R 5 are each independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl optionally substituted by one, two, or three groups independently selected from halogen, cyano, and hydroxyl, and —(C 1 -C 6 alkylene)-(phenyl) optionally substituted by one, two, or three groups independently selected from halogen, cyano, —CF 3 , —OH, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

each R 6 is independently selected from the group consisting of halogen, —N(R 12 )R 13 , —CF 3 , C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 10 and R 11 are each independently selected from the group consisting of hydrogen, and C 1 -C 3 alkyl; or R 10 and R 11 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocyclic ring optionally substituted by C 1 -C 6 alkyl or —CO 2 H;

each R 12 and R 13 are each independently selected from the group consisting of hydrogen, and C 1 -C 3 alkyl;

n is 1 or 2; and

p is 0, 1, or 2.

2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen or halogen.

3. The compound of claim 2 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is —N(R 10 )R 11 .

4. The compound of claim 3 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 and R 11 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocyclic ring optionally substituted by C 1 -C 6 alkyl or —CO 2 H.

5. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 and R 11 together with the nitrogen atom to which they are attached, form an unsubstituted pyrrolidine ring.

6. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 and R 11 together with the nitrogen atom to which they are attached, form an unsubstituted piperidine ring.

7. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 and R 11 together with the nitrogen atom to which they are attached, form a piperazine ring optionally substituted by C 1 -C 6 alkyl.

8. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 10 and R 11 together with the nitrogen atom to which they are attached, form a morpholine ring.

9. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 is hydrogen.

10. The compound of claim 9 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 5 is unsubstituted —CH 2 -phenyl.

11. The compound of claim 9 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 is hydrogen.

12. The compound of claim 11 , or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1.

13. The compound of claim 12 , or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0.

14. The compound of claim 13 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen.

15. The compound of claim 13 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is halogen.

16. The compound of claim 15 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is Cl.

17. A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from:

(S)-4-isopropyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(pyrrolidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-isopropyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-isopropyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(morpholine-4-carbonyl)phenyl)piperazine-1-carboxylate;

(R)-4-isopropyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(pyrrolidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(R)-4-isopropyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(R)-4-isopropyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(morpholine-4-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(pyrrolidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(morpholine-4-carbonyl)phenyl)piperazine-1-carboxylate;

(R)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(pyrrolidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(R)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(R)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(morpholine-4-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(4-methylpiperazine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-4-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(dimethylcarbamoyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-5-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(3-carbamoyl-2-chlorophenyl)piperazine-1-carboxylate;

(S)-4-benzyl-3-methyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-benzyl-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)-1,4-diazepane-1-carboxylate;

(S)-2,5-dioxo-4-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate;

(S)-4-(4-chlorobenzyl)-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate; and

(S)-4-(4-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl 4-(2-chloro-3-(piperidine-1-carbonyl)phenyl)piperazine-1-carboxylate.

18. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient or binder, and a compound of claim 1 ; or a pharmaceutically acceptable salt or solvate thereof.

19. A method of therapeutically treating a disease, disorder or condition in a mammal that would benefit from lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibition comprising administering to the mammal a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, or solvate thereof, according to claim 1 .

20. The method of claim 19 , wherein the disease, disorder or condition in a mammal is ischemia, traumatic brain injury, multiple sclerosis, diabetes, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and cancer.