The discovery and initial optimisation of pyrrole-2-carboxamides as inhibitors of p38alpha MAP kinase.
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.
Down
Kenneth
K
GlaxoSmithKline R&D, Medicines Research Centre, Stevenage, Hertfordshire, UK. kenneth.d.down@gsk.com
Bamborough
Paul
P
Alder
Catherine
C
Campbell
Amanda
A
Christopher
John A
JA
Gerelle
Maria
M
Ludbrook
Steve
S
Mallett
Dave
D
Mellor
Geoff
G
Miller
David D
DD
Pearson
Rosannah
R
Ray
Keith
K
Solanke
Yemisi
Y
Somers
Don
D
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D000577:Amides; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D048051:p38 Mitogen-Activated Protein Kinases