Fused thiophene derivatives as MEK inhibitors

Victoria E Laing; Daniel C Brookings; Rachel J Carbery; Jose Gascon Simorte; Martin C Hutchings; Barry J Langham; Martin A Lowe; Rodger A Allen; Joanne R Fetterman; James Turner; Christoph Meier; Jeff Kennedy; Mark Merriman

doi:10.1016/j.bmcl.2011.10.105

Fused thiophene derivatives as MEK inhibitors

Bioorg Med Chem Lett. 2012 Jan 1;22(1):472-5. doi: 10.1016/j.bmcl.2011.10.105. Epub 2011 Nov 6.

Authors

Victoria E Laing¹, Daniel C Brookings, Rachel J Carbery, Jose Gascon Simorte, Martin C Hutchings, Barry J Langham, Martin A Lowe, Rodger A Allen, Joanne R Fetterman, James Turner, Christoph Meier, Jeff Kennedy, Mark Merriman

Affiliation

¹ Department of Medicinal Chemistry, UCB Pharma, 216 Bath Road, Slough, Berkshire SL1 3WE, UK. victoria.jackson@ucb.com

PMID: 22119475
DOI: 10.1016/j.bmcl.2011.10.105

Abstract

A number of novel fused thiophene derivatives have been prepared and identified as potent inhibitors of MEK. The SAR data of selected examples and the in vivo profiling of compound 13 h demonstrates the functional activity of this class of compounds in HT-29 PK/PD models.

MeSH terms

Animals
Cell Line, Tumor
Chemistry, Pharmaceutical / methods*
Crystallography, X-Ray / methods
Drug Design
Drug Screening Assays, Antitumor
Humans
Inhibitory Concentration 50
MAP Kinase Kinase Kinases / antagonists & inhibitors*
Mice
Models, Chemical
Phosphorylation
Protein Kinase Inhibitors / pharmacology*
Static Electricity
Structure-Activity Relationship
Thiophenes / chemistry*
Time Factors

Substances

Protein Kinase Inhibitors
Thiophenes
MAP Kinase Kinase Kinases