p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression
| Autor: | Donald O. Somers, Ann Louise Walker, Katherine Louise Jones, Duncan S. Holmes, Giovanni Vitulli, Nicola Mary Aston, Paul Bamborough, Penny A. Smee, Chris D. Edwards, Jacqueline B. Buckton, Vipulkumar Kantibhai Patel |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Molecular Conformation Administration Oral Mitogen-Activated Protein Kinase 14 chemistry.chemical_compound Mice Biosynthesis Drug Discovery Transferase Animals Humans Protein Kinase Inhibitors MAPK14 chemistry.chemical_classification Virtual screening biology Chemistry Biphenyl Compounds Biological activity Amides Arthritis Experimental Rats Enzyme Biochemistry Mitogen-activated protein kinase biology.protein Molecular Medicine Tumor necrosis factor alpha |
| Zdroj: | Journal of medicinal chemistry. 52(20) |
| ISSN: | 1520-4804 |
| Popis: | p38alpha MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNFalpha and IL-1beta at a translational and transcriptional level. In this paper, we describe how we have optimized a series of novel p38alpha/beta inhibitors using crystal structures of our inhibitors bound to p38alpha, classical medicinal chemistry, and modeling of virtual libraries to derive a molecule suitable for progression into clinical development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|