Indolin-2-one p38α inhibitors I: design, profiling and crystallographic binding mode

Paul Eastwood; Jacob González; Elena Gómez; Bernat Vidal; Francisco Caturla; Ramón Roca; Cristina Balagué; Adelina Orellana; María Domínguez

doi:10.1016/j.bmcl.2011.05.114

Indolin-2-one p38α inhibitors I: design, profiling and crystallographic binding mode

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4130-3. doi: 10.1016/j.bmcl.2011.05.114. Epub 2011 Jun 6.

Authors

Paul Eastwood¹, Jacob González, Elena Gómez, Bernat Vidal, Francisco Caturla, Ramón Roca, Cristina Balagué, Adelina Orellana, María Domínguez

Affiliation

¹ Almirall Research Center, Almirall S.A., Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain. paul.eastwood@almirall.com

PMID: 21696951
DOI: 10.1016/j.bmcl.2011.05.114

Abstract

The use of structure-based design and molecular modeling led to the discovery of indolin-2-one derivatives as potent and selective p38α inhibitors. The predicted binding mode was confirmed by X-ray crystallography.

MeSH terms

Animals
Binding Sites
Crystallography, X-Ray
Drug Design*
Humans
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / pharmacokinetics
Microsomes, Liver / metabolism
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
Mitogen-Activated Protein Kinase 14 / metabolism
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacokinetics
Protein Structure, Tertiary
Rats
Structure-Activity Relationship

Substances

Indoles
Protein Kinase Inhibitors
indolin-2-one
Mitogen-Activated Protein Kinase 14