Curcumin derivatives
View Patent ↗A compound has Formula VIII where, X is —C(O)R, —C(O)OR, —CN, —NO 2 , —S(O) 2 R′, —P(O)(OR) 2 ; each R is individually H, alkyl, or alkenyl; R′ is alkyl or akenyl; R 1 is aryl, alkenyl, arylalkenyl, heterocyclyl, or heteroaryl; and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are individually H, alkoxy, or hydroxy. In some cases, X is NO 2 . Pharmaceutical compositions of the compound of Formula VIII with a pharmaceutically acceptable carrier may be prepared. The compounds may be used for inhibition of cyclooxygenase-2.
1. A compound of Formula VIII:
wherein:
X is —C(O)R, —C(O)OR, —CN, —NO 2 , —S(O) 2 R′, —P(O)(OR) 2 ;
each R is individually H, alkyl, aryl, or alkenyl;
R′ is alkyl, aryl, or akenyl;
R 1 is aryl, alkenyl, arylalkenyl, heterocyclyl, or heteroaryl; and
R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are individually H, alkoxy, or hydroxy.
2. The compound of claim 1 , wherein R 1 is phenyl, alkenyl, thiophenyl, or furyl.
3. The compound of claim 1 , wherein R 4 and R 9 are alkoxy.
4. The compound of claim 1 , wherein R 2 , R 3 , R 6 , R 7 , R 10 , and R 11 are H.
5. The compound of claim 1 , wherein X is NO 2 .
6. The compound of claim 1 , wherein Formula VIII is 3,5-bis(4-methoxyphenyl)-2-((e)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanone; 3-(3,4-dimethoxyphenyl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanone; 5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-phenylcyclohexanone; 3-(4-chlorophenyl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanone; 5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-(thiophen-2-yl)cyclohexanone; 3-(benzo[a][1,3]dioxol-5-yl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanone; 3-(furan-2-yl)-5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitrocyclohexanone; 5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-(3-nitrophenyl)cyclohexanone; 5-(4-methoxyphenyl)-2-((E)-3-(4-methoxyphenyl)acryloyl)-4-nitro-3-styrylcyclohexanone; 5-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-((E)-3-(3,4-dimethoxyphenyl)acryloyl)-4-nitrocyclohexanone; 5-(4-hydroxy-3-methoxyphenyl)-2-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)-3-(4-methoxyphenyl)-4-nitrocyclohexanone; or 3-(4-methoxyphenyl)-4-nitro-5-phenyl-2-((E)-3-phenylacryloyl)cyclohexanone.
7. A method of preparing a compound of Formula VIII comprising:
reacting a compound of Formula VI with a nitroalkene in the presence of a base, wherein:
the nitroalkene has formula R 1 CH═CHNO 2 ;
R 1 is aryl, alkene, heterocyclyl, or heteroaryl; and
R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are individually H, alkoxy, or hydroxy.
8. The method of claim 7 , wherein the base is a metal alkoxide, metal hydroxide, metal carbonate, metal oxide, metal amide, an amine, a hindered amine, or a mixture of any two or more thereof.
9. The method of claim 7 , wherein the compound of Formula VIII, has the stereoselective conformation of the compound of Formula VIII*:
10. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.