1,3-disubstituted-2- thioxo-imidazolidine-4,5-dione derivatives useful in the treatment of atherosclerosis
View Patent ↗Antiatherosclerotic compounds of Formula I are provided: wherein: R is lower alkyl, alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′; R′ is lower alkyl; n is an integer of 1–3; Ar is phenyl, or phenyl substituted with one or more of halogen, lower alkyl, alkenyl, alkynyl, alkoxy, perfluoroalkyl, perfluoroalkoxy, or alkylthio; and pharmaceutically acceptable salts thereof.
1. Antiatherosclerotic compounds of Formula I
wherein:
R is lower alkyl, alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′;
R′ is lower alkyl;
n is an integer of 1–3;
Ar is phenyl substituted with one or more of halogen, lower alkyl, alkenyl, alkynyl, perfluoroalkyl, perfluoroalkoxy, or alkylthio; and pharmaceutically acceptable salts thereof.
2. The antiatherosclerotic compounds of claim 1 wherein:
R is lower alkyl, alkynyl, or —O—(CH 2 ) n —COOR′;
R′ is lower alkyl;
n is an integer of 1–3; and
Ar is phenyl substituted with halogen, lower alkyl or alkylthio; and pharmaceutically acceptable salts thereof.
3. The compound of claim 1 which is ethyl 2-{[3-(5-chloro-2 methylphenyl)-4,5-dioxo-2-thioxo-1-imidazolidinyl]oxy}acetate.
4. The compound of claim 1 which is 1-(4-chloro-2-methylphenyl)-3-ethyl-2-thioxo-4,5-imidazolidinedione.
5. The compound of claim 1 which is 1-(5-chloro-2-methylphenyl)-3-methyl-2-thioxo-4,5-imidazolidinedione.
6. The compound of claim 1 which is 1-(2,6-dimethylphenyl)-3-methyl-2-thioxo-4,5-imidazolidinedione.
7. The compound of claim 1 which is 1-(5-chloro-2-methylphenyl)-3-(2-propynyl)-2-thioxo-4,5-imidazolidinedione.
8. The compound of claim 1 which is 1-ethyl-3-(5-fluoro-2-methylphenyl)-2-thioxo-4,5-imidazolidinedione.
9. The compound of claim 1 which is 1-(2,6-dimethylphenyl)-3-methyl-2-thioxo-4,5-imidazolidinedione.
10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of Formula I:
wherein:
R is lower alkyl, alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′;
R′ is lower alkyl;
n is an integer of 1–3;
Ar is phenyl substituted with one or more of halogen, lower alkyl, alkenyl, alkynyl, perfluoroalkyl, perfluoroalkoxy, or alkylthio; and pharmaceutically acceptable salts thereof.
11. A method for treating atherosclerosis in a mammal in need thereof, comprising administering to said mammal an anti-atherosclerotic effective amount of a compound of Formula I:
wherein:
R is alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′;
R′ is lower alkyl;
n is an integer of 1–3;
Ar is phenyl, or phenyl substituted with one or more of halogen, lower alkyl, alkenyl, alkynyl, alkoxy, perfluoroalkyl, perfluoroalkoxy, or alkylthio; and pharmaceutically acceptable salts thereof.
12. The compounds of claim 1 , wherein R is straight chain lower alkyl, alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′.
13. The compounds of claim 1 , wherein R is —CH 3 , —CH 2 CH 3 , alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′.
14. The compounds of claim 1 , wherein R is lower alkyl, alkynyl, or —O—(CH 2 ) n —COOR′.
15. The compounds of claim 14 , wherein R is straight chain lower alkyl, alkynyl, or —O—(CH 2 ) n —COOR′.
16. The compounds of claim 14 , wherein R is —CH 3 , —CH 2 CH 3 , alkynyl, or —O—(CH 2 ) n —COOR′.
17. The compounds of claim 14 , wherein R is —CH 3 , —CH 2 CH 3 , —CH 2 C≡CH, or —O—CH 2 —COOCH 2 CH 3 .
18. The compounds of claim 2 wherein R is straight chain lower alkyl, alkynyl, or —O—(CH 2 ) n —COOR′.
19. The compounds of claim 2 wherein R is CH 3 , CH 2 CH 3 , alkynyl, or —O—(CH 2 ) n —COOR′.
20. The antiatherosclerotic compounds of claim 2 wherein R is —CH 3 , —CH 2 CH 3 , —CH 2 C≡CH, or —O—(CH 2 ) n —COO CH 2 CH 3 .
21. A method for treating atherosclerosis in a mammal in need thereof, comprising administering to said mammal an anti-atherosclerotic effective amount of a compound of Formula I:
wherein:
R is lower alkyl, alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′;
R′ is lower alkyl;
n is an integer of 1–3;
Ar is phenyl, or phenyl substituted with one or more of halogen, lower alkyl, alkenyl, alkynyl, alkoxy, perfluoroalkyl, perfluoroalkoxy, or alkylthio; and pharmaceutically acceptable salts thereof.
22. A compound having Formula I
wherein:
R is lower alkyl, alkenyl, alkynyl, or —O—(CH 2 ) n —COOR′;
R′ is lower alkyl;
n is an integer of 1–3;
Ar is phenyl substituted with one or more of halogen, lower alkyl, alkenyl, alkynyl, perfluoroalkyl, perfluoroalkoxy, or alkylthio; and pharmaceutically acceptable salts thereof.
23. The compound of claim 22 , wherein:
R is lower alkyl, alkynyl, or —O—(CH 2 ) n —COOR′;
R′ is lower alkyl;
n is an integer of 1–3; and
Ar is phenyl substituted with halogen, lower alkyl or alkylthio; and pharmaceutically acceptable salts thereof.
24. The compound of claim 22 , which is ethyl 2-{[3-(5-chloro-2methylphenyl)-4,5-dioxo-2-thioxo-1-imidazolidinyl]oxy}acetate.
25. The compound of claim 22 , which is 1-(4-chloro-2-methylphenyl)-3-ethyl-2-thioxo-4,5-imidazolidinedione.
26. The compound of claim 22 , which is 1-(5-chloro-2-methylphenyl)-3-methyl-2-thioxo-4,5-imidazolidinedione.
27. The compound of claim 22 , which is 1-(2,6-dimethylphenyl)-3-methyl-2-thioxo-4,5-imidazolidinedione.
28. The compound of claim 22 , which is 1-(5-chloro-2-methylphenyl)-3-(2-propynyl)-2-thioxo-4,5-imidazolidinedione.
29. The compound of claim 22 , which is 1-ethyl-3-(5-fluoro-2-methylphenyl)-2-thioxo-4,5-imidazolidinedione.
30. The compound of claim 22 , which is 1-(2,6-dimethylphenyl)-3-methyl-2-thioxo-4,5-imidazolidinedione.