ps-540446 and Inflammation

ps-540446 has been researched along with Inflammation* in 1 studies

Other Studies

1 other study(ies) available for ps-540446 and Inflammation

Article	Year
Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases. Journal of medicinal chemistry, 2010, Sep-23, Volume: 53, Issue:18 The discovery and characterization of 7k (BMS-582949), a highly selective p38α MAP kinase inhibitor that is currently in phase II clinical trials for the treatment of rheumatoid arthritis, is described. A key to the discovery was the rational substitution of N-cyclopropyl for N-methoxy in 1a, a previously reported clinical candidate p38α inhibitor. Unlike alkyl and other cycloalkyls, the sp(2) character of the cyclopropyl group can confer improved H-bonding characteristics to the directly substituted amide NH. Inhibitor 7k is slightly less active than 1a in the p38α enzymatic assay but displays a superior pharmacokinetic profile and, as such, was more effective in both the acute murine model of inflammation and pseudoestablished rat AA model. The binding mode of 7k with p38α was confirmed by X-ray crystallographic analysis. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Biological Availability; Caco-2 Cells; Crystallography, X-Ray; Female; Humans; Hydrogen Bonding; In Vitro Techniques; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Microsomes, Liver; Mitogen-Activated Protein Kinase 14; Models, Molecular; Molecular Conformation; Protein Binding; Pyrroles; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Stereoisomerism; Structure-Activity Relationship; Triazines; Tumor Necrosis Factor-alpha	2010

Article

Year

Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases.

Journal of medicinal chemistry, 2010, Sep-23, Volume: 53, Issue:18

The discovery and characterization of 7k (BMS-582949), a highly selective p38α MAP kinase inhibitor that is currently in phase II clinical trials for the treatment of rheumatoid arthritis, is described. A key to the discovery was the rational substitution of N-cyclopropyl for N-methoxy in 1a, a previously reported clinical candidate p38α inhibitor. Unlike alkyl and other cycloalkyls, the sp(2) character of the cyclopropyl group can confer improved H-bonding characteristics to the directly substituted amide NH. Inhibitor 7k is slightly less active than 1a in the p38α enzymatic assay but displays a superior pharmacokinetic profile and, as such, was more effective in both the acute murine model of inflammation and pseudoestablished rat AA model. The binding mode of 7k with p38α was confirmed by X-ray crystallographic analysis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Biological Availability; Caco-2 Cells; Crystallography, X-Ray; Female; Humans; Hydrogen Bonding; In Vitro Techniques; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Microsomes, Liver; Mitogen-Activated Protein Kinase 14; Models, Molecular; Molecular Conformation; Protein Binding; Pyrroles; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Stereoisomerism; Structure-Activity Relationship; Triazines; Tumor Necrosis Factor-alpha

2010