Compounds > 1-(3-tert-butyl-1-methylpyrazol-5-yl)-3-(4-chlorophenyl)urea

1-(3-tert-butyl-1-methylpyrazol-5-yl)-3-(4-chlorophenyl)urea and Autoimmune-Diseases

1-(3-tert-butyl-1-methylpyrazol-5-yl)-3-(4-chlorophenyl)urea has been researched along with Autoimmune-Diseases* in 1 studies

Other Studies

1 other study(ies) available for 1-(3-tert-butyl-1-methylpyrazol-5-yl)-3-(4-chlorophenyl)urea and Autoimmune-Diseases

Article	Year
The kinetics of binding to p38MAP kinase by analogues of BIRB 796. Bioorganic & medicinal chemistry letters, 2003, Sep-15, Volume: 13, Issue:18 BIRB 796, a member of the N-pyrazole-N'-naphthly urea class of p38MAPK inhibitors, binds to the kinase with both slow association and dissociation rates. Prior to binding, the kinase undergoes a reorganization of the activation loop exposing a critical binding domain. We demonstrate that, independent of the loop movement, association rates are governed by low energy conformations of the inhibitor and polar functionality on the tolyl ring. As anticipated, the dissociation rates of the inhibitors from the kinase are slowed by lipophilic and hydrogen bond interactions. The value of structure-kinetic relationships (SKR) in drug design is discussed. Topics: Autoimmune Diseases; Drug Design; Enzyme Inhibitors; Humans; Hydrophobic and Hydrophilic Interactions; Inhibitory Concentration 50; Kinetics; Mitogen-Activated Protein Kinases; Naphthalenes; p38 Mitogen-Activated Protein Kinases; Protein Binding; Protein Structure, Tertiary; Pyrazoles; Structure-Activity Relationship	2003

Article

Year

The kinetics of binding to p38MAP kinase by analogues of BIRB 796.

Bioorganic & medicinal chemistry letters, 2003, Sep-15, Volume: 13, Issue:18

BIRB 796, a member of the N-pyrazole-N'-naphthly urea class of p38MAPK inhibitors, binds to the kinase with both slow association and dissociation rates. Prior to binding, the kinase undergoes a reorganization of the activation loop exposing a critical binding domain. We demonstrate that, independent of the loop movement, association rates are governed by low energy conformations of the inhibitor and polar functionality on the tolyl ring. As anticipated, the dissociation rates of the inhibitors from the kinase are slowed by lipophilic and hydrogen bond interactions. The value of structure-kinetic relationships (SKR) in drug design is discussed.

Topics: Autoimmune Diseases; Drug Design; Enzyme Inhibitors; Humans; Hydrophobic and Hydrophilic Interactions; Inhibitory Concentration 50; Kinetics; Mitogen-Activated Protein Kinases; Naphthalenes; p38 Mitogen-Activated Protein Kinases; Protein Binding; Protein Structure, Tertiary; Pyrazoles; Structure-Activity Relationship

2003