Pyrimidinone inhibitors of lipoprotein-associated phospholipase A2
The present invention relates to new pyrimidinone inhibitors of lipoprotein-associated phospholipase A2 activity, pharmaceutical compositions thereof, and methods of use thereof
1. A compound of structural Formula I
or a pharmaceutically acceptable salt thereof, wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , and R 38 are each independently selected from the group consisting of hydrogen and deuterium; and
at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , and R 38 independently has deuterium enrichment of no less than about 10%.
2. The compound as recited in claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , and R 38 independently has deuterium enrichment of no less than about 50%.
3. The compound as recited in claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , and R 38 independently has deuterium enrichment of no less than about 90%.
4. The compound as recited in claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , and R 38 independently has deuterium enrichment of no less than about 98%.
5. The compound as recited in claim 1 wherein said compound has a structural formula selected from the group consisting of
wherein each position represented as D has deuterium enrichment of no less than about 10%.
6. The compound as recited in claim 5 wherein each position represented as D has deuterium enrichment of no less than about 50%.
7. The compound as recited in claim 5 wherein each position represented as D has deuterium enrichment of no less than about 90%.
8. The compound as recited in claim 5 wherein each position represented as D has deuterium enrichment of no less than about 98%.
9. The compound as recited in claim 5 wherein said compound has a structural formula selected from the group consisting of
10. The compound as recited in claim 9 wherein said compound has the structural formula:
11. The compound as recited in claim 9 wherein said compound has the structural formula:
12. The compound as recited in claim 9 wherein said compound has the structural formula:
13. The compound as recited in claim 9 wherein said compound has the structural formula:
14. The compound as recited in claim 9 wherein said compound has the structural formula:
15. The compound as recited in claim 9 wherein said compound has the structural formula:
16. A pharmaceutical composition comprising a compound as recited in claim 1 together with a pharmaceutically acceptable carrier.