Method of modulating stress-activated protein kinase system
AssigneeIntermune, Inc.
InventorsLawrence M. Blatt, Scott D. Seiwert, Leonid Beigelman, Ramachandran Radhakrishnan, Karl Kossen, Vladimir Serebryany
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Abstract
Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system.
Claims59
A compound of Genus Ia
- wherein
- R1, R3, and R4 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, substituted C1-C10 alkyl, C1-C10 alkenyl, C1-C10 haloalkyl, C1-C10 nitroalkyl, C1-C10 thioalkyl, C1-C10 hydroxyalkyl, C1-C10 alkoxy, phenyl, substituted phenyl, halogen, hydroxyl, C1-C10 alkoxyalkyl, C1-C10 carboxy, and C1-C10 alkoxycarbonyl;
- R2 is selected from the group consisting of substituted C1-C10 alkyl, C1-C10 alkenyl, C1-C10 haloalkyl, C1-C10 nitroalkyl, C1-C10 thioalkyl, C1-C10 hydroxyalkyl, C1-C10 alkoxy, substituted phenyl, halogen, hydroxyl, C1-C10 alkoxyalkyl, C1-C10 carboxy, and C1-C10 alkoxycarbonyl;
- and
- X1 X2, X3, X4 and X5 are independently selected from the group consisting of hydrogen, halogen, C1-C10 alkoxy, and hydroxyl.
A compound having the structure of Genus Ia:
- wherein
- R2 is selected from the group consisting of H, substituted C1-C10 alkyl, C1-C10 alkenyl, C1-C10 haloalkyl, C1-C10 nitroalkyl, C1-C10 thioalkyl, C1-C10 hydroxyalkyl, C1-C10 alkoxy, phenyl, substituted phenyl, halogen, hydroxyl, C1-C10 alkoxyalkyl, C1-C10 carboxy, C1-C10 alkoxycarbonyl, CO-uronide, CO-monosaccharide, CO-oligosaccharide, and CO-polysaccharide;
- R1 is H;
- R3 is selected from the group consisting of H, C1-C10 alkyl, substituted C1-C10 alkyl, C1-C10 alkenyl, C1-C10 haloalkyl, C1-C10 nitroalkyl, C1-C10 thioalkyl, hydroxyalkyl, C1-C10 alkoxy, phenyl, substituted phenyl, halogen, hydroxyl, C1-C10 alkoxyalkyl, C1-C10 carboxy, C1-C10 alkoxycarbonyl, CO-uronide, CO-monosaccharide, CO-oligosaccharide, and CO-polysaccharide;
- R4 is selected from the group consisting of H, halogen, and hydroxyl;
- and
- X1, X2, X3, X4, and X5 are independently selected from the group consisting of H, halogen, C1-C10 alkoxy, and hydroxy, wherein at least one of X1, X2, X3, X4, and X5 is not H.
A compound having the structure of Genus Ia:
- wherein
- R2 is selected from the group consisting of phenyl and substituted phenyl;
- R1, R3, and R4 are H;
- and
- X1, X2, X3, X4, and X5 are independently selected from the group consisting of H, halogen, C1-C10 alkoxy, and hydroxy.
A method of treating an inflammatory or fibrotic condition, comprising administering to a patient in need thereof a compound having the structure of Genus Ia:
- wherein
- R2 is selected from the group consisting of H, substituted C1-C10 alkyl, C1-C10 alkenyl, C1-C10 haloalkyl, C1-C10 nitroalkyl, C1-C10 thioalkyl, C1-C10 hydroxyalkyl, C10 alkoxy, phenyl, substituted phenyl, halogen, hydroxyl, C1-C10 alkoxyalkyl, C1-C10 carboxy, C1-C10 alkoxycarbonyl, CO-uronide, CO-monosaccharide, CO-oligosaccharide, and CO-polysaccharide;
- R1, R3, and R4 are independently selected from the group consisting of H, C1-C10 alkyl, substituted C1-C10 alkyl, C1-C10 alkenyl, C1-C10 haloalkyl, C1-C10 nitroalkyl, C1-C10 thioalkyl, C1-C10 hydroxyalkyl, C1-C10 alkoxy, phenyl, substituted phenyl, halogen, hydroxyl, C1-C10 alkoxyalkyl, C1-C10 carboxy, C1-C10 alkoxycarbonyl, CO-uronide, CO-monosaccharide, CO-oligosaccharide, and CO-polysaccharide;
- and
- X1, X2, X3, X4, and X5 are independently selected from the group consisting of H, halogen, C1-C10 alkoxy, and hydroxy, wherein at least one of X1, X2, X3, X4, and X5 is not H.
Dependencies are inferred from the claim text.