The discovery and initial optimisation of pyrrole-2-carboxamides as inhibitors of p38alpha MAP kinase

Kenneth Down; Paul Bamborough; Catherine Alder; Amanda Campbell; John A Christopher; Maria Gerelle; Steve Ludbrook; Dave Mallett; Geoff Mellor; David D Miller; Rosannah Pearson; Keith Ray; Yemisi Solanke; Don Somers

doi:10.1016/j.bmcl.2010.05.011

The discovery and initial optimisation of pyrrole-2-carboxamides as inhibitors of p38alpha MAP kinase

Bioorg Med Chem Lett. 2010 Jul 1;20(13):3936-40. doi: 10.1016/j.bmcl.2010.05.011. Epub 2010 May 10.

Authors

Kenneth Down¹, Paul Bamborough, Catherine Alder, Amanda Campbell, John A Christopher, Maria Gerelle, Steve Ludbrook, Dave Mallett, Geoff Mellor, David D Miller, Rosannah Pearson, Keith Ray, Yemisi Solanke, Don Somers

Affiliation

¹ GlaxoSmithKline R&D, Medicines Research Centre, Stevenage, Hertfordshire, UK. kenneth.d.down@gsk.com

PMID: 20570148
DOI: 10.1016/j.bmcl.2010.05.011

Abstract

A novel pyrrole-2-carboxamide series of p38alpha inhibitors, discovered through the application of virtual screening, is presented. Following evaluation of activity, selectivity and developability properties of commercially available analogues, a synthesis program enabled rapid assessment of the series' suitability for further lead optimisation studies.

MeSH terms

Amides / chemical synthesis
Amides / chemistry
Amides / pharmacology*
Dose-Response Relationship, Drug
Drug Discovery*
High-Throughput Screening Assays
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyrroles / chemistry*
Stereoisomerism
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

Amides
Protein Kinase Inhibitors
Pyrroles
p38 Mitogen-Activated Protein Kinases