| abstract |
57 Compounds of the formulan nwhereinn R 1 is hydrogen or -(CH 2 ) m COOR 2 ; R 2 is hydrogen, (R 6 ) 2 N(CH 2 ) 2 -, R 6 COOCH 2 - or -CH 2 CON(CH 2 CH 2 0H) 2 ; R 3 is hydrogen, nitro, hydroxy, amino, CH 3 (CH 2 ) n S(O) 0-2 -, CH 3 (CH 2 ) n -,CH 3 (CH 2 ) n O- ,R 5 COO-, RsOOC- ,R 5 HNCOO-, RsNHCO-, RsCONH-, RsNHCONH-, [CH 3 (CH 2 ) n]2 NCO- , CH 3 (CH 2 ) n CHOHCH 2 0-, (2-quinolinyl)methoxy, oleyloxy, linoleyloxy, R 8 OOC(CH 2 ) t -O, (R 6 0) 2 PO(CH 2 )pO- , (HO) (R 6 0)PO(CH 2 )pO- , R 6 [O(CH 2 ) 2 ] q O- , R 7 (CH 2 )pO-, or -O(CH 2 ) p -pyridinium + (OH - ); R 4 is CH 3 (CH 2 ) n - , CH 3 (CH 2 ) n O- , CF 3 SO 2 NH-, RsCOO-, RsOOC- ,R 5 HNCOO-, RsNHCO-, RsCONH-RsNHCONH-, [CH 3 (CH 2 ) n]2 NCO-, CH 3 (CH 2 ) n CHOHCH 2 0-, carboxy, (2-quinolinyl)methoxy, oleyloxy, linoleyloxy, R 8 OOC(CH 2 ) t O-, R 6 [O(CH 2 ) 2 ] q O- , or R 7 (CH 2 )pO-; R 5 is CH 3 (CH 2 ) n -, 1-adamantyl or diphenylmethyl; R 6 is lower alkyl; R 7 is 1- or 2 -naphthyloxy, 1-, 2- or 3-pyridinyloxy, 2,3- or 3,4-dihydroxyphenyl, 6,7-dihydroxy-2-naphthyl, phenyl, phenoxy or substituted phenyl or phenoxy, wherein the substituent is selected from the group consisting of lower alkyl, lower alkoxy, hydroxy, nitro, amino, halo, R 6 S(O) 0-2 -, carboxy, carboxy-lower alkyl or phenyl; R 8 is hydrogen or lower alkyl; n is an integer from 0 to 17; m is an integer from 1 to 3; t is an integer from 1 to 10; p is an integer from 2 to 18, and q is an integer from 1 to 6; nand when R 2 is hydrogen, a pharmaceutically acceptable salt thereof with a base, are potent inhibitors of phospholipases A 2 (PLA 2 's) and are therefore useful in the treatment of inflammatory diseases, such as psosiasis, inflammatory bowel disease, asthma, allergy, arthritis, dermatitis, gout, pulmonary disease, myocardial ischemia/reperfusion, and trauma induced inflammation, such as spinal cord injury. |