Anti-Inflammatory Compounds and Use Thereof

Abstract

Compounds of the general formula are disclosed with activity towards treating diseases related to inflammation, such as cancer, neurodegenerative and cardiovascular diseases. Pharmaceutical compositions and methods of use are also disclosed.

1 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein
 A is an optionally substituted aliphatic, alicyclic, aryl, aralkyl, heteroaliphatic, heterocyclic, or heteroaromatic group; 
 X 1  is selected from —O—, —NH—, and —S—, wherein either X 1  is —NH— or A is a radical of a non-steroidal anti-inflammatory compound; 
 B is an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aralkyl, or heteroaromatic group optionally substituted with one or more X 2  moieties, with the proviso that B is not described by 
 
       
         
           
           
               
               
           
         
         each X 2  is, independently, selected from hydrogen, halogen, hydroxyl, alkoxyl, —CN; an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, aralkyl, or heteroaromatic moiety; —OR R , —S(═O)—R d , —NR b R c , —C(═O)R a  and —C(═O)OR a ; 
         n is 0-2; 
         R a , for each occurrence, is independently selected from hydrogen and an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, aralkyl, or heteroaromatic moiety; 
         each of R b  and R c , for each occurrence, is independently selected from hydrogen; hydroxyl, SO 2 R d , and an aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, aralkyl, heteroaromatic or acyl moiety; 
         R d , for each occurrence, is independently selected from hydrogen, —N(Re) 2 , aliphatic, aryl and heteroaryl, 
         R e , for each occurrence, is independently hydrogen or aliphatic; and 
         R R  is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aryl, aralkyl, heteroaromatic or acyl moiety; and 
         D is —O—P(O)(OR f ) 2  or —O—P(OR g ) 2 , wherein each R f  and R g  is a substituted or unsubstituted alkyl of 1-6 carbon atoms.