CURCUMIN DERIVATIVES

• US 20110160276A1
• Filed: 03/04/2010
• Published: 06/30/2011
• Est. Priority Date: 12/30/2009
• Status: Active Grant

• Current Assignee: Indian Institute of Technology Bombay
• Original Assignee: Indian Institute of Technology Bombay
• Inventors: Namboothiri, Irishi N.N., Jose, Deena, Ayyagari, Narasimham
• Granted Patent: US 8,410,177 B2
• Time in Patent Office: Days
• US Class Current: 514/438
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 317/58 Radicals substituted by nitrogen atoms nitro radicals C07D317/52
• CPC Class Codes: C07D 333/20 by nitrogen atoms nitro, nitroso radicals C07D333/12

Abstract

A compound has Formula VIII where, X is —C(O)R, —C(O)OR, —CN, —NO₂, —S(O)₂R′, —P(O)(OR)₂; each R is individually H, alkyl, or alkenyl; R′ is alkyl or akenyl; R¹ is aryl, alkenyl, arylalkenyl, heterocyclyl, or heteroaryl; and R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, and R¹¹ are individually H, alkoxy, or hydroxy. In some cases, X is NO₂.

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.

Claims

1. A compound of Formula VIII:

2. The compound of claim 1, wherein R¹ is phenyl, alkenyl, thiophenyl, or furyl.

3. The compound of claim 1, wherein R⁴ and R⁹ are alkoxy.

4. The compound of claim 1, wherein R², R³, R⁶, R⁷, R¹⁰, and R¹¹ are H.

5. The compound of claim 1, wherein X is NO₂.

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.

10. A pharmaceutical composition comprising the compound of claim 1, and a pharmaceutically acceptable carrier.

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;

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*: