Substituted 4-(Indazol-3-yl)phenols

Abstract

This invention provides compound of formulae I or II having the structure wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are as defined in the specification or a pharmaceutically acceptable salt thereof which are useful for the treatment of the inflammatory component of diseases and are particularly useful in treating atherosclerosis, myocardial infarction, congestive heart failure, inflammatory bowel disease, arthritis, type II diabetes, and autoimmune diseases such as multiple sclerosis and rheumatiod arthritis.

1 . A compound of formulae I or II having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, cycloalkyi of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S;  
 R 2 , R 3 , R 4 , and R 5 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CN, —NO 2 , —CHO, or —CO 2 R 11 ;  
 R 6 , R 7 , R 8 , and R 9 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CO 2  R 11 , aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S wherein the nitrogen or sulfur atoms are optionally oxidized and nitrogen is optionally quaternized;  
 R 10  is hydrogen, —CO R 11 , —CONH R 11 , —P(═O)(OH)OR 11 , or —CO(CH 2 ) n CH(NHR 12 )CO 2 R 11 ;  
 R 11  is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-20 carbon atoms, or arylalkyl of 7-26 carbon atoms; R 12  is hydrogen or —CO 2 R 11 ;  
 n=0-3,  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       2 . The compound according to  claim 1 , wherein 
 R 1  is alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, cycloalkyl of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S;    R 2  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, or halogen;    R 7  and R 9 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, hydroxy, halogen, trifluoromethyl, —CO 2 R 11 , aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S;    or a pharmaceutical acceptable salt thereof.    
   
   
       3 . The compound according to  claim 2 , wherein 
 R 1  is alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, cycloalkyl of 3-8 carbon atoms, or cycloalkenyl of 4-8 carbon atoms;    R 2  is hydrogen, alkyl of 1-6 carbon atoms, halogen, or hydroxy;    R 9  is alkyl of 1-6 carbon atoms, halogen, trifluoromethyl, —CO 2 R 11 , aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S;    R 10  is hydrogen;    or a pharmaceutically acceptable salt thereof.    
   
   
       4 . The compound according to  claim 3 , wherein 
 R 1  is alkyl of 1-6 carbon atoms or alkenyl of 2-7 carbon atoms;    R 9  is alkyl of 1-6 carbon atoms, halogen, or trifluoromethyl; or a pharmaceutically acceptable salt thereof.    
   
   
       5 . The compound according to  claim 1 , which is 
 a) 4-(6-chloro-5-fluoro-1-methyl-1H-indazol-3-yl)phenol;    b) 4-(7-chloro-1-methyl-1H-indazol-3-yl)phenol;    c) 4-(1H-indazol-3-yl)phenol;    d) 4-(6-chloro-5-fluoro-1H-indazol-3-yl)phenol;    e) 4-(6-chloro-1H-indazol-3-yl)phenol;    f) 4-(1-butyl-1H-indazol-3-yl)phenol;    g) 4-(1-benzyl-7-chloro-1H-indazol-3-yl)phenol;    h) 4-[1-benzyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    i) 4-(1-benzyl-7-fluoro-1H-indazol-3-yl)phenol;    j) 4-[1-benzyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    k) 4-(1-benzyl-7-chloro-1H-indazol-3-yl)benzene-1,3-diol;    l) 4-(1-benzyl-7-fluoro-1H-indazol-3-yl)-1,3-benzenediol;    m) 4-[1-(2-hydroxyethyl)-1H-indazol-3-yl]phenol;    n) 4-[1-(2-hydroxyethyl)-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    o) 4-[1-methyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    p) 4-(5-fluoro-1-methyl-1H-indazol-3-yl)phenol;    q) 4-[1-methyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    r) 4-(7-chloro-1-methyl-1H-indazol-3-yl)benzene-1,3-diol;    s) 4-[1-methyl-5-(trifluoromethyl)-1H-indazol-3-yl]phenol;    t) 4-(5-fluoro-1-methyl-1H-indazol-3-yl)benzene-1,3-diol;    u) 4-[1-methyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,2-diol;    v) 4-(1-butyl-7-chloro-1H-indazol-3-yl)phenol;    w) 4-[1-benzyl-5-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    x) 4-(1-benzyl-1H-indazol-3-yl)benzene-1,3-diol;    y) 4-[7-fluoro-1-(2-hydroxyethyl)-1H-indazol-3-yl]phenol;    z) 4-[5-fluoro-1-(2-hydroxyethyl)-1H-indazol-3-yl]benzene-1,3-diol;    aa) 4-[1-(2-chlorophenyl)-6-hydroxy-1H-indazol-3-yl]benzene-1,3-diol;    bb) 4-[6-hydroxy-1-(4-methoxyphenyl)-1H-indazol-3-yl]benzene-1,3-diol;    cc) 4-[6-hydroxy-1-(2-methoxyphenyl)-1H-indazol-3-yl]benzene-1,3-diol;    dd) 4-{6-hydroxy-1-[4-(trifluoromethoxy)phenyl]-1H-indazol-3-yl}benzene-1,3-diol;    ee) 4-[1-(3-bromophenyl)-6-hydroxy-1H-indazol-3-yl]benzene-1,3-diol;    ff) 4-[1-(4-bromophenyl)-6-hydroxy-1H-indazol-3-yl]benzene-1,3-diol;    gg) 4-[3-(2,4-dihydroxyphenyl)-6-hydroxy-1H-indazol-1-yl]benzonitrile;    hh) 4-[1-(3-chlorophenyl)-6-hydroxy-1H-indazol-3-yl]benzene-1,3-diol;    ii) 4-(1-ethyl-6-hydroxy-1H-indazol-3-yl)benzene-1,3-diol;    jj) 4-(6-hydroxy-1-propyl-1H-indazol-3-yl)benzene-1,3-diol;    kk) 4-(1-butyl-6-hydroxy-1H-indazol-3-yl)benzene-1,3-diol;    ll) 4-(1-cyclohexyl-6-hydroxy-1H-indazol-3-yl)benzene-1,3-diol;    mm) 4-[6-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indazol-3-yl]benzene-1,3-diol;    nn) 4-[1-(3-fluorophenyl)-6-hydroxy-1H-indazol-3-yl]benzene-1,3-diol;    oo) 4-[6-hydroxy-1-(4-methylphenyl)-1H-indazol-3-yl]benzene-1,3-diol;    pp) 4-[1-(2-fluorophenyl)-6-hydroxy-1H-indazol-3-yl]benzene-1,3-diol;    qq) 4-[6-hydroxy-1-(3-methylphenyl)-1H-indazol-3-yl]benzene-1,3-diol;    rr) 4-(7-chloro-1-cyclohexyl-1H-indazol-3-yl)phenol;    ss) 4-[1-(4-bromophenyl)-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    tt) 4-[1-cyclohexyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    uu) 4-(7-methyl-1H-indazol-3-yl)phenol;    vv) 4-[1-(3-chloro-4-fluorophenyl)-6-hydroxy-1H-indazol-3-yl]benzene-1,3-diol;    ww) 4-{6-hydroxy-1-[3-(trifluoromethyl)phenyl]-1H-indazol-3-yl}benzene-1,3-diol;    xx) 4-[6-hydroxy-1-(3-nitrophenyl)-1H-indazol-3-yl]benzene-1,3-diol;    yy) 4-[6-hydroxy-1-(4-isopropylphenyl)-1H-indazol-3-yl]benzene-1,3-diol;    zz) 4-{6-hydroxy-1-[4-(methylsulfonyl)phenyl]-1H-indazol-3-yl}benzene-1,3-diol;    aaa) 4-(7-methyl-1-propyl-1H-indazol-3-yl)phenol;    bbb) 4-(1-isopropyl-7-methyl-1H-indazol-3-yl)phenol;    ccc) 4-(7-chloro-1-pentyl-1H-indazol-3-yl)phenol;    ddd) 4-(7-chloro-1-propyl-1H-indazol-3-yl)phenol;    eee) 4-(7-chloro-1-isopropyl-1H-indazol-3-yl)phenol;    fff) 4-[1-pentyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    ggg) 4-[1-isopropyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    hhh) 4-[1-propyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    iii) 4-(7-methyl-2-propyl-2H-indazol-3-yl)phenol;    jjj) 4-[2-isopropyl-7-methyl-2H-indazol-3-yl]phenol;    kkk) 4-(7-chloro-2-pentyl-2H-indazol-3-yl)phenol;    lll) 4-(7-chloro-2-propyl-2H-indazol-3-yl)phenol;    mmm) 4-(7-chloro-2-isopropyl-2H-indazol-3-yl)phenol;    nnn) 4-[1-butyl-6-(trifluoromethyl)-1H-indazol-3-yl]phenol;    ooo) 4-(1-butyl-6-chloro-1H-indazol-3-yl)phenol;    ppp) 4-(7-fluoro-1-methyl-1H-indazol-3-yl)phenol;    qqq) 4-(1H-indazol-3-yl)benzene-1,2-diol;    rrr) 4-(7-fluoro-1H-indazol-3-yl)phenol;    sss) 4-[1-butyl-5-(trifluoromethyl)-1H-indazol-3-yl]phenol;    ttt) 4-(1-cyclohexyl-7-fluoro-1H-indazol-3-yl)phenol;    uuu) 4-(1-allyl-7-fluoro-1H-indazol-3-yl)phenol;    vvv) 4-(1-allyl-7-methyl-1H-indazol-3-yl)phenol;    www) 4-[1-allyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    xxx) 4-(7-chloro-1-cyclopentyl-1H-indazol-3-yl)phenol;    yyy) 4-(7-fluoro-1-propyl-1H-indazol-3-yl)phenol;    zzz) 4-(7-fluoro-1-isopropyl-1H-indazol-3-yl)phenol;    aaaa) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)phenol;    bbbb) 4-[1-butyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    cccc) 4-(1-butyl-7-fluoro-1H-indazol-3-yl)phenol;    dddd) 4-[2-allyl-7-(trifluoromethyl)-2H-indazol-3-yl]phenol;    eeee) 4-(7-chloro-2-cyclopentyl-2H-indazol-3-yl)phenol;    ffff) 4-(2-cyclopentyl-7-fluoro-2H-indazol-3-yl)phenol;    gggg) 4-(7-fluoro-2-isopropyl-2H-indazol-3-yl)phenol;    hhhh) 4-(7-fluoro-2-propyl-2H-indazol-3-yl)phenol;    iiii) 4-[7-fluoro-1-(3,3,3-trifluoropropyl)-1H-indazol-3-yl)phenol;    jjjj) 4-[1-allyl-7-(trifluoromethyl)-1H-indazol-3-yl]-3-methylphenol;    kkkk) 3-methyl-4-[1-propyl-7-(trifluoromethyl)-1H-indazol-3-yl]phenol;    llll) 4-[1-allyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    mmmm) 4-[1-pentyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    nnnn) 4-[2-allyl-7-(trifluoromethyl)-2H-indazol-3-yl]-3-methylphenol;    oooo) 4-[2-allyl-7-(trifluoromethyl)-2H-indazol-3-yl]-1,3-benzenediol;    pppp) 4-(7-chloro-1-isopropyl-1H-indazol-3-yl)-3-methylphenol;    qqqq) 4-(7-chloro-2-isopropyl-2H-indazol-3-yl)-3-methylphenol;    rrrr) 4-(7-chloro-1-propyl-1H-indazol-3-yl)-3-methylphenol;    ssss) 4-(7-chloro-2-propyl-2H-indazol-3-yl)-3-methylphenol;    tttt) 4-(1-allyl-7-chloro-1H-indazol-3-yl)-3-methylphenol;    uuuu) 4-(2-allyl-7-chloro-2H-indazol-3-yl)-3-methylphenol;    vvvv) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)-2-methylphenol;    wwww) 4-(7-chloro-1-cyclopentyl-1H-indazol-3-yl)-3-methylphenol;    xxxx) 4-(7-chloro-1-isopropyl-1H-indazol-3-yl)benzene-1,3-diol;    yyyy) 4-(1-allyl-7-chloro-1H-indazol-3-yl)benzene-1,3-diol;    zzzz) 4-[1-isopropyl-7-(trifluoromethyl)-1H-indazol-3-yl]-3-methylphenol;    aaaaa) 4-(1-isopropyl-7-thien-3-yl-1H-indazol-3-yl)phenol;    bbbbb) 4-(1-isopropyl-7-thien-2-yl-1H-indazol-3-yl)phenol;    ccccc) 4-{1-isopropyl-7-[4-(methylthio)phenyl]-1H-indazol-3-yl }phenol;    ddddd) 4-{7-[4-(hydroxymethyl)phenyl]-1-isopropyl-1H-indazol-3-yl}phenol;    eeeee) 4-[3-(4-hydroxyphenyl)-1-isopropyl-1H-indazol-7-yl]benzene-1,2-diol;    fffff) 4-[7-(4-ethylphenyl)-1-isopropyl-1H-indazol-3-yl]phenol;    ggggg) 4-[7-(1,1′-biphenyl-4-yl)-1-isopropyl-1H-indazol-3-yl]phenol;    hhhhh) 4-[7-(2-chlorophenyl)-1-isopropyl-1H-indazol-3-yl]phenol;    iiiii) 4-[1-isopropyl-7-(2-methylphenyl)-1H-indazol-3-yl]phenol;    jjjjj) 4-(1-isopropyl-7-phenyl-1H-indazol-3-yl)phenol;    kkkkk) 4-{1-cyclopentyl-7-[4-(trifluoromethyl)phenyl]-1H-indazol-3-yl}phenol;    lllll) 4-(1-cyclopentyl-7-thien-2-yl-1H-indazol-3-yl)phenol;    mmmmm) 4-[1-cyclopentyl-3-(4-hydroxyphenyl)-1H-indazol-7-yl]benzene-1,2-diol;    nnnnn) 4-[1-cyclopentyl-7-(4-ethylphenyl)-1H-indazol-3-yl]phenol;    ooooo) 4-[7-(2-chlorophenyl)-1-cyclopentyl-1H-indazol-3-yl]phenol;    ppppp) 4-[1-cyclopentyl-7-(2-furyl)-1H-indazol-3-yl]phenol;    qqqqq) 4-[1-cyclopentyl-7-(2-methylphenyl)-1H-indazol-3-yl]phenol;    rrrrr) 4-(1-cyclopentyl-7-phenyl-1H-indazol-3-yl)phenol;    sssss) 4-(1-isopropyl-7-thien-3-yl-1H-indazol-3-yl)-3-methylphenol;    ttttt) 4-{7-[(1 E)-hept-1-enyl]-1-isopropyl-1H-indazol-3-yl}-3-methylphenol;    uuuuu) 4-{7-[4-(hydroxymethyl)phenyl]-1-isopropyl-1H-indazol-3-yl}-3-methylphenol;    vvvvv) 4-[3-(4-hydroxy-2-methylphenyl)-1-isopropyl-1H-indazol-7-yl]benzene-1,2-diol;    wwwww) 4-[7-(4-ethylphenyl)-1-isopropyl-1H-indazol-3-yl]-3-methylphenol;    xxxxx) 4-[7-(1,1′-biphenyl-4-yl)-1-isopropyl-1H-indazol-3-yl]-3-methylphenol;    yyyyy) 4-[7-(2-chlorophenyl)-1-isopropyl-1H-indazol-3-yl]-3-methylphenol;    zzzzz) 4-[7-(2-furyl)-1-isopropyl-1H-indazol-3-yl]-3-methylphenol;    aaaaaa) 4-[1-isopropyl-7-(2-methylphenyl)-1H-indazol-3-yl]-3-methylphenol;    bbbbbb) 4-(1-isopropyl-7-phenyl-1H-indazol-3-yl)-3-methylphenol;    cccccc) 4-{1-cyclopentyl-7-[4-(methylthio)phenyl]-1H-indazol-3-yl }-3 -methy I phenol;    dddddd) 4-{1-cyclopentyl-7-[(1 E)-hept-1-enyl]-1H-indazol-3-yl}-3-methylphenol;    eeeeee) 4-[1-cyclopentyl-3-(4-hydroxy-2-methylphenyl)-1H-indazol-7-yl]benzene-1,2-diol;    ffffff) 4-[1-cyclopentyl-7-(4-ethylphenyl)-1H-indazol-3-yl]-3-methylphenol;    gggggg) 4-[7-(1,1′-biphenyl-4-yl)-1-cyclopentyl-1H-indazol-3-yl]-3-methylphenol;    hhhhhh) 4-[7-(2-chlorophenyl)-1-cyclopentyl-1H-indazol-3-yl]-3-methylphenol;    iiiiii) 4-[1-cyclopentyl-7-(2-furyl)-1H-indazol-3-yl]-3-methylphenol;    jjjjjj) 4-[1-cyclopentyl-7-(2-methylphenyl)-1H-indazol-3-yl]-3-methylphenol;    kkkkkk) 4-(1-cyclopentyl-7-phenyl-1H-indazol-3-yl)-3-methylphenol;    llllll) 4-[7-(1-benzothien-2-yl)-1-cyclopentyl-1H-indazol-3-yl]-3-methylphenol;    mmmmmm) 4-[7-(2-furyl)-1-isopropyl-1H-indazol-3-yl]phenol;    nnnnnn) 4-(7-fluoro-1-propyl-1H-indazol-3-yl)-3-methylphenol;    oooooo) 4-(7-fluoro-2-propyl-2H-indazol-3-yl)-3-methylphenol;    pppppp) 4-(7-fluoro-1-isopropyl-1H-indazol-3-yl)-3-methylphenol;    qqqqqq) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)benzene-1,3-diol;    rrrrrr) 4-(7-fluoro-1-isobutyl-1H-indazol-3-yl)-3-methylphenol;    ssssss) 4-(7-fluoro-1-isopropyl-1H-indazol-3-yl)benzene-1,3-diol;    tttttt) 4-(7-fluoro-2-isopropyl-2H-indazol-3-yl)benzene-1,3-diol;    uuuuuu) 4-(7-fluoro-1-isobutyl-1H-indazol-3-yl)benzene-1,3-diol;    vvvvvv) 4-[3-(4-hydroxyphenyl)-1-propyl-1H-indazol-7-yl]phenol;    wwwwww) 4-[7-(4-fluorophenyl)-1-propyl-1H-indazol-3-yl]phenol;    xxxxxx) 4-(7-morpholin-4-yl-1-propyl-1H-indazol-3-yl)phenol;    yyyyyy) 4-(7-phenyl-2-propyl-2H-indazol-3-yl)phenol;    zzzzzz) 4-(7-phenyl-1-propyl-1H-indazol-3-yl)phenol;    aaaaaaa) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)phenyl pivalate;    bbbbbbb) 4-(7-chloro-1-propyl-1H-indazol-3-yl)phenyl 3,3-dimethylbutanoate;    ccccccc) 4-(7-chloro-1-propyl-1H-indazol-3-yl)phenyl propionate;    ddddddd) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)phenyl acetate;    eeeeeee) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)phenyl propionate;    fffffff) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)phenyl N-(tert-butoxycarbonyl)glycylglycinate;    ggggggg) 1-tert-butyl 5-[4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)phenyl]N-(tert-butoxycarbonyl)-L-glutamate;    hhhhhhh) 4-(1-cyclopentyl-7-fluoro-1H-indazol-3-yl)phenyl ethylcarbamate;    iiiiiii) 4-(7-chloro-1-thien-3-yl-1H-indazol-3-yl)phenol;    jjjjjjj) 4-[1-isopropyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    kkkkkkk) methyl 3-(4-hydroxyphenyl)-2-isopropyl-2H-indazole-7-carboxylate;    lllllll) 4-[1-cyclopentyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    mmmmmmm) 4-[1-(cyclohexylmethyl)-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    nnnnnnn) 4-[1-isobutyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    ooooooo) 4-[1-cyclobutyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol;    ppppppp) 4-[1-(2-ethylbutyl)-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol,    or a pharmaceutically acceptable salt thereof.    
   
   
       6 . A pharmaceutical composition, which comprises a compound of  claim 1  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
   
   
       7 . A method of treating or inhibiting chronic inflammatory disease, rheumatoid arthritis, spondyloarthropathies, osteoarthritis, psoriatic arthritis, juvenile arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, indeterminate colitis, psoriasis, asthma, chronic obstructive pulmonary disease, stroke, ischemia, reperfusion injury, type II diabetes or sepsis in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formulae I or II having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, cycloalkyi of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S;  
 R 2 , R 3 , R 4 , and R 5 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CN, —NO 2 , —CHO, or —CO 2 R 11 ;  
 R 6 , R 7 , R 8 , and R 9 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CO 2 Rii, aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S wherein the nitrogen or sulfur atoms are optionally oxidized and nitrogen is optionally quaternized;  
 R 10  is hydrogen, —COR 11 , —CONHR 11 , —P(═O)(OH)OR 11  or —CO(CH 2 ) n CH(NHR 12 )CO 2 R 11 ;  
 R 11  is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-20 carbon atoms, or arylalkyl of 7-26 carbon atoms; R 12  is hydrogen or —CO 2 R 11 ;  
 n=0-3,  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       8 . The method of  claim 7  wherein the method is for treating or inhibiting rheumatoid arthritis, spondyloarthropathies, osteoarthritis, psoriatic arthritis, or juvenile arthritis in a mammal in need thereof.  
   
   
       9 . The method of  claim 7  wherein the method is for treating or inhibiting inflammatory bowel disease, Crohn's disease, ulcerative colitis, or indeterminate colitis in a mammal in need thereof.  
   
   
       10 . The method of  claim 7  wherein the method is for treating or inhibiting psoriasis in a mammal in need thereof.  
   
   
       11 . The method of  claim 7  wherein the method is for treating or inhibiting asthma or chronic obstructive pulmonary disease in a mammal in need thereof.  
   
   
       12 . The method of  claim 7  wherein the method is for treating or inhibiting stroke, ischemia, or reperfusion injury in a mammal in need thereof.  
   
   
       13 . A method of lowering cholesterol, triglycerides, Lp(a), and LDL levels; inhibiting or treating hypercholesteremia, hyperlipidemia, cardiovascular disease, atherosclerosis, acute coronary syndrome, peripheral vascular disease, restenosis, or vasospasm in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formulae I or II having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, cycloalkyi of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S;  
 R 2 , R 3 , R 4 , and R 5 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CN, —NO 2 , —CHO, or —CO 2 R 11 ;  
 R 6 , R 7 , R 8 , and R 9 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CO 2 R 11 , aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S wherein the nitrogen or sulfur atoms are optionally oxidized and nitrogen is optionally quaternized;  
 R 10  is hydrogen, —COR 11 , —CONHR 11 , —P(═O)(OH)O R 11 , or —CO(CH 2 ) n CH(NHR 12 )CO 2 R 11 ;  
 R 11  is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-20 carbon atoms, or arylalkyl of 7-26 carbon atoms; R 12  is hydrogen or —CO 2 R 11 ;  
 n=0-3,  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       14 . A method of treating or inhibiting Alzheimer's disease, cognitive decline, or senile dementia in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formulae I or II having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, cycloalkyi of 3-8 carbon atoms, cycloalkenyl of 4-8 carbon atoms, aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S;  
 R 2 , R 3 , R 4 , and R 5 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CN, —NO 2 , —CHO, or —CO 2 R 11 ;  
 R 6 , R 7 , R 8 , and R 9 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, hydroxy, alkoxy of 1-6 carbon atoms, aryloxy of 6-20 carbon atoms, halogen, trifluoromethyl, —CO 2 R 11 , aryl of 6-20 carbon atoms, arylalkyl of 7-26 carbon atoms, or a saturated, unsaturated, or partially unsaturated heterocyclic ring or ring system of 4-14 atoms, containing 1-4 heteroatoms selected from N, O, and S wherein the nitrogen or sulfur atoms are optionally oxidized and nitrogen is optionally quaternized;  
 R 10  is hydrogen, —COR 11 , —CONHR 11 , —P(═O)(OH)OR 11 , or —CO(CH 2 ) n CH(NHR 12 )CO 2 R 11 ;  
 R 11  is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-20 carbon atoms, or arylalkyi of 7-26 carbon atoms; R 12  is hydrogen or —CO 2 Rn;  
 n=0-3,  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       15 . The method of  claim 7  wherein the method is for treating or inhibiting type II diabetes in a mammal in need thereof.  
   
   
       16 . The method of  claim 7  wherein the method is for treating or inhibiting sepsis in a mammal in need thereof.  
   
   
       17 . The method of  claim 7  wherein the method is for treating or inhibiting chronic inflammatory disease in a mammal in need thereof.