O-pyridinequinone derivatives, the composition containing the derivatives, the process for preparation of the derivatives and the use of the derivatives

#This application is a 371 of PCT/CN2003/000711 filed on Aug. 22, 2003, published on Mar. 4, 2004 under publication number WO 2004/018427 A1 which claims priority benefits from Chinese Patent Application Number 02130161.1 filed Aug. 23, 2002.

#The present invention relates to a compound having anti-inflammatory activity and which may be used as an agent selectively inhibiting cyclooxygenase-2 (COX-2) in inflammatory cells, to a method of preparing the compound, to a composition comprising the compound and to a use thereof. Specifically, the present invention relates to a compound derivative having o-pyridinequinone structure, a method for preparation thereof, a composition comprising the derivative and a use thereof.

#Aspirin, marketed by Bayer AG (Germany) in last-century, is a famous anti-inflammatory, antipyretic, and analgesic agent. Although the commonly used anti-inflammatory agents such as aspirin have favorable anti-inflammatory, antipyretic, and analgesic effects, they exhibit apparent toxicity on gastrointestinal tracts and kidneys. The toxic and side effects of aspirin are due to that aspirin is not a specific COX-2 inhibiting agent.

#FIG. 1 indicates that a specific compound in the present invention, 5,6-di(m-acetylphenylamino)-2,3-pyridindione (sample), has almost no inhibition effect on COX-1, whereas all of the three positive controls have much higher inhibition effects.

#FIG. 2 shows that the compound in the present invention, 5,6-di(m-acetylphenylamino)-2,3-pyridindione (sample), inhibits the growth of the COLO205 cells ex vivo, whereas both of the two positive controls have lower inhibition effects than the compound.

#The present invention is further described in detail by way of examples of chemical and biological experiments. These examples are illustrative and are not intended to limit the scope of the invention in any manner. The scope of the present invention is defined in the CLAIMS.

#Method 1: 2,3-dihydroxypyridine (0.0027 mol), aniline (0.0054 mol), and NaIO3 (0.0009 mol) were dissolved in 160 ml water/acetone (80:1, v/v) solvent. The reaction mixture was stirred for 2 hours, and maintained still overnight. Product was then filtered and recrystallized with petroleum ether. 5,6-diphenylamino-2,3-pyridindione can then be obtained in a brown yellow powder. The yield was 25%-45%.

#Method 2: 2,3-dihydroxypyridine in Method 1 was substituted with 2,3-dihydroxy-5-bromopyridine, whereas other steps remained the same as in Method 1. The same product can be obtained, and the yield was 35%-50%.