Anti-inflammatory medicaments

1 - 83 . (canceled)

84 . A compound having the formula

wherein:

A is selected from the group consisting of phenyl, naphthyl, pyridyl, pyrimidyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, isoquinolyl, quinolyl, benzothiazolyl, benzofuranyl, benzothienyl, pyrazolylpyrimidinyl, imidazopyrimidinyl, purinyl, and

where each W 1 is individually selected from the group consisting of —CH— and —N—;

D is selected from the group consisting of phenyl, pyrazolyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, furyl, oxadiazolyl, thiadiazolyl, thienyl, pyridyl, and pyrimidyl;

E is selected from the group consisting of phenyl, pyridinyl, and pyrimidinyl;

Y is selected from the group consisting of —O—, —S—, —NR 6 —, —NR 6 SO 2 —, —NR 6 CO—, alkynyls, alkenyls, alkylenes, —O(CH 2 ) h —, and —NR 6 (CH 2 ) h —, where h is individually selected from the group consisting of 1, 2, 3, or 4, and where for each of alkylenes, —O(CH 2 ) h —, and —NR 6 (CH 2 ) h —, one of the methylene groups present therein may be optionally double-bonded to a side-chain oxo group except that where —O(CH 2 ) h — the introduction of the side-chain oxo group does not form an ester moiety;

t is 0 or 1;

Q is

each R 4 group is individually selected from the group consisting of —H, alkyls, aminoalkyls, alkoxyalkyls, aryls, aralkyls, heterocyclyls, and heterocyclylalkyls except when the R 4 substituent places a heteroatom on an alpha-carbon directly attached to a ring nitrogen on Q;

when two R 4 groups are bonded with the same atom, the two R 4 groups optionally form an alicyclic or heterocyclic 4-7 membered ring;

each R 6 is individually selected from the group consisting of —H and alkyls;

R 7 ″ is selected from the group consisting of alkyls, aryls, heterocyclyls, and perfluoroalkyls;

and wherein A or Q is optionally substituted with one or more R 7 ′ substituents selected from the group consisting of —H, alkyls, aryls, heterocyclyls, alkylaminos, arylaminos, cycloalkylaminos, heterocyclylaminos, hydroxys, alkoxys, aryloxys, alkylthios, arthylthios, cyanos, halogens, nitros, alkylsulfinyls, alkylsulfonyls, aminosulfonyls, and perfluoroalkyls.

85 . The compound of claim 84 , wherein A is phenyl substituted by one or more R 7 ′ substituents, said R 7 ′ substituents being halogens.

86 . The compound of claim 84 , wherein A is an R 7 ′-substituted naphthyl.

87 . The compound of claim 84 , where R 7 ″ is selected from the group consisting of aryls and heterocyclyls.

88 . A method of modulating the activation state of a p38-alpha kinase comprising the step of contacting said kinase with a molecule having the formula

wherein:

A is selected from the group consisting of phenyl, naphthyl, pyridyl, pyrimidyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, isoquinolyl, quinolyl, benzothiazolyl, benzofuranyl, benzothienyl, pyrazolylpyrimidinyl, imidazopyrimidinyl, purinyl, and

where each W 1 is individually selected from the group consisting of —CH— and —N—;

D is selected from the group consisting of phenyl, pyrazolyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, furyl, oxadiazolyl, thiadiazolyl, thienyl, pyridyl, and pyrimidyl;

E is selected from the group consisting of phenyl, pyridinyl, and pyrimidinyl;

Y is selected from the group consisting of —O—, —S—, —NR 6 —, —NR 6 SO 2 —, —NR 6 CO—, alkynyls, alkenyls, alkylenes, —O(CH 2 ) h —, and —NR 6 (CH 2 ) h —, where h is individually selected from the group consisting of 1, 2, 3, or 4, and where for each of alkylenes, —O(CH 2 ) h —, and —NR 6 (CH 2 ) h —, one of the methylene groups present therein may be optionally double-bonded to a side-chain oxo group except that where —O(CH 2 ) h — the introduction of the side-chain oxo group does not form an ester moiety;

t is 0 or 1;

Q is

each R 4 group is individually selected from the group consisting of —H, alkyls, aminoalkyls, alkoxyalkyls, aryls, aralkyls, heterocyclyls, and heterocyclylalkyls except when the R 4 substituent places a heteroatom on an alpha-carbon directly attached to a ring nitrogen on Q;

when two R 4 groups are bonded with the same atom, the two R 4 groups optionally form an alicyclic or heterocyclic 4-7 membered ring;

each R 6 is individually selected from the group consisting of —H and alkyls;

R 7 ″ is selected from the group consisting of alkyls, aryls, heterocyclyls, and perfluoroalkyls;

and wherein A or Q is optionally substituted with one or more R 7 ′ substituents selected from the group consisting of —H, alkyls, aryls, heterocyclyls, alkylaminos, arylaminos, cycloalkylaminos, heterocyclylaminos, hydroxys, alkoxys, aryloxys, alkylthios, arthylthios, cyanos, halogens, nitros, alkylsulfinyls, alkylsulfonyls, aminosulfonyls, and perfluoroalkyls.

89 . The method of claim 88 , wherein A is phenyl substituted by one or more R 7 ′ substituents, said R 7 ′ substituents being halogens.

90 . The compound of claim 88 , wherein A is an R 7 ′-substituted naphthyl.

91 . The compound of claim 88 , where R 7 ″ is selected from the group consisting of aryls and heterocyclyls.

92 . An adduct comprising a molecule bound with a kinase, said molecule having the formula

wherein:

A is selected from the group consisting of phenyl, naphthyl, pyridyl, pyrimidyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, isoquinolyl, quinolyl, benzothiazolyl, benzofuranyl, benzothienyl, pyrazolylpyrimidinyl, imidazopyrimidinyl, purinyl, and

where each W 1 is individually selected from the group consisting of —CH— and —N—;

D is selected from the group consisting of phenyl, pyrazolyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, furyl, oxadiazolyl, thiadiazolyl, thienyl, pyridyl, and pyrimidyl;

E is selected from the group consisting of phenyl, pyridinyl, and pyrimidinyl;

Y is selected from the group consisting of —O—, —S—, —NR 6 —, —NR 6 (SO 2 —, —NR 6 CO—, alkynyls, alkenyls, alkylenes, —O(CH 2 ) h —, and —NR 6 (CH 2 ) h —, where h is individually selected from the group consisting of 1, 2, 3, or 4, and where for each of alkylenes, —O(CH 2 ) h —, and —NR 6 (CH 2 ) h —, one of the methylene groups present therein may be optionally double-bonded to a side-chain oxo group except that where —O(CH 2 ) h — the introduction of the side-chain oxo group does not form an ester moiety;

t is 0 or 1;

Q is

each R 4 group is individually selected from the group consisting of —H, alkyls, aminoalkyls, alkoxyalkyls, aryls, aralkyls, heterocyclyls, and heterocyclylalkyls except when the R 4 substituent places a heteroatom on an alpha-carbon directly attached to a ring nitrogen on Q;

when two R 4 groups are bonded with the same atom, the two R 4 groups optionally form an alicyclic or heterocyclic 4-7 membered ring;

each R 6 is individually selected from the group consisting of —H and alkyls;

R 7 ″ is selected from the group consisting of alkyls, aryls, heterocyclyls, and perfluoroalkyls;

and wherein A or Q is optionally substituted with one or more R 7 ′ substituents selected from the group consisting of —H, alkyls, aryls, heterocyclyls, alkylaminos, arylaminos, cycloalkylaminos, heterocyclylaminos, hydroxys, alkoxys, aryloxys, alkylthios, arthylthios, cyanos, halogens, nitros, alkylsulfinyls, alkylsulfonyls, aminosulfonyls, and perfluoroalkyls.

93 . The adduct of claim 92 , wherein A is phenyl substituted by one or more R 7 ′ substituents, said R 7 ′ substituents being halogens.

94 . The adduct of claim 92 , wherein A is an R 7 ′-substituted naphthyl.

95 . The adduct of claim 92 , where R 7 ″ is selected from the group consisting of aryls and heterocyclyls.

96 . A method of treating an individual suffering from a condition selected from the group consisting of human inflammation, rheumatoid arthritis, rheumatoid spondylitis, osteo-arthritis, asthma, gouty arthritis, sepsis, septic shock, endotoxic shock, Gram-negative sepsis, toxic shock syndrome, adult respiratory distress syndrome, stroke, reperfusion injury, neural trauma, neural ischemia, psoriasis, restenosis, chronic pulmonary inflammatory disease, bone resorptive diseases, graft-versus-host reaction, Crohn's disease, ulcerative colitis, inflammatory bowel disease, pyresis, and combinations thereof, said method comprising the step of administering to said individual a compound of the formula of claim 84 .