Compositions and treatments for inhibiting kinase and/or HMG-CoA reductase

1 - 56 . (canceled)

57 . A composition comprising a compound of formula III

wherein A is a covalent bond or a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2-6 carbons, optionally containing a heteroatom, such as O, N, or S;

X comprises a lipophilic moiety;

Y is hydrogen or lower alkyl; and

Z is hydrogen or hydroxy; wherein X is a lipophilic moiety of a pyrrole HMG-CoA reductase inhibitor, a pyrazole HMG-CoA reductase inhibitor, an imidazole HMG-CoA reductase inhibitor, an indole HMG-CoA reductase inhibitor, a pyridine HMG-CoA reductase inhibitor, a pyrimidine HMG-CoA reductase inhibitor, or a quinoline HMG-CoA reductase inhibitor.

58 - 84 . (canceled)

85 . A composition comprising a compound of formula IV

wherein A is a covalent bond or a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2-6 carbons, optionally containing a heteroatom, such as O, N, or S;

P 6 is hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkaryl, substituted alkaryl, benyl, substituted benzyl, napthylmethylene, or substituted napthlymethylene;

X comprises a lipophilic moiety;

Y is hydrogen or lower alkyl; and

Z is hydrogen or hydroxy;

wherein said lipophilic moiety X comprises a MAP kinase inhibitor or a lipophilic moiety of said MAP kinase inhibitor.

86 - 90 . (canceled)

91 . The composition as recited in claim 90 wherein X is a pyrazole MAP kinase inhibitor, an oxazole MAP kinase inhibitor, an imidazole MAP kinase inhibitor, a pyrrolo[2,3-b] pyrimidine MAP kinase inhibitor, a diazaisoquinolinone MAP kinase inhibitor, a 1,2-pyrazine MAP kinase inhibitor, a pyrrole MAP kinase inhibitor, a 4-aminobenzophenone MAP kinase inhibitor, a 3-amidobenzamide MAP kinase inhibitor, a pyridine MAP kinase inhibitor, a pyrimidino[4,5-d]pyrimidinone MAP kinase inhibitor, or an indole MAP kinase inhibitor.

92 - 104 . (canceled)

105 . The composition as recited in claim 104 wherein X is a lipophilic moiety of a pyrrole HMG-CoA reductase inhibitor, a pyrazole HMG-CoA reductase inhibitor, an imidazole HMG-CoA reductase inhibitor, an indole HMG-CoA reductase inhibitor, a pyridine HMG-CoA reductase inhibitor, a pyrimidine HMG-CoA reductase inhibitor, or a quinoline HMG-CoA reductase inhibitor.

106 - 118 . (canceled)

119 . A method of treating an inflammatory condition comprising administering to a subject an effective amount of at least one of said compounds as recited in claim 57 or 85 .

120 . The method as recited in claim 119 wherein said administering inhibits a MAP kinase and/or an HMG CoA reductase.

121 - 124 . (canceled)

125 . A method of treating an inflammatory condition comprising administering an effective amount of a statin lactone to a subject wherein said lactone inhibits a MAP kinase and said lactone is not substantially hydrolyzed to an acid form.

126 . The method as recited in claim 125 wherein said lactone does not substantially inhibit HMG CoA reductase.

127 . The method as recited in claim 125 wherein said administering is carried out by topical application.

128 . The method as recited in claim 125 wherein said administering is carried out by rectal administration.

129 - 157 . (canceled)

158 . A method of making a composition for inhibiting a MAP kinase and/or an HMG CoA reductase, comprising:

designing a compound of formula I/II

wherein X comprises a lipophilic moiety; wherein A is a covalent bond or a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2-6 carbons, optionally containing a heteroatom, such as O, N, or S; Y is hydrogen or lower alkyl; and Z is hydrogen or hydroxy;

testing whether said compound inhibits said MAP kinase and said HMG CoA reductase; and

using said compound in making a composition for inhibiting said MAP kinase and/or said HMG CoA reductase.

159 . The composition as recited in claim 158 wherein A is a covalent bond, methylene, 1,2-oxamethylene, 1,2-ethylene, 1,2-ethynylene, 1,2-ethenylene, 1,3-propylene or 1,3-propenylene.

160 . The method as recited in claim 158 wherein said lipophilic moiety X comprises a MAP kinase inhibitor, a lipophilic moiety thereof, or an analog thereof.

161 . The method as recited in claim 160 wherein said lipophilic moiety X is selected on the basis of structural similarity to a lipohilic moiety of an HMG-CoA reductase inhibitor.

162 . The method as recited in claim 160 wherein said lipophilic moiety X is selected on the basis of structural compatibility with binding to an HMG-CoA reductase.

163 . The method as recited in claim 158 wherein said lipophilic moiety X comprises an analog of a lipophilic moiety of an HMG-CoA reductase inhibitor.

164 . The method as recited in claim 163 wherein said lipophilic moiety X is selected on the basis of structural similarity to a lipophilic moiety of a MAP kinase inhibitor.

165 . The method as recited in claim 163 wherein said lipophilic moiety X is selected on the basis of structural compatibility with binding to a MAP kinase.

166 . The method as recited in claim 158 wherein said lipophilic moiety X is randomly selected.

167 . The method as recited in claim 158 wherein said testing step involves computational prediction of said inhibition.

168 . The method as recited in claim 158 wherein said testing step involves synthesizing said designed compounds and evaluating said inhibition in a cell-free assay.

169 . The method as recited in claim 158 wherein said testing step involves synthesizing said designed compounds and evaluating said inhibition in a whole cell assay.

170 . The method as recited in claim 158 wherein said testing step involves synthesizing said designed compounds and evaluating said inhibition in an in vivo model.