Discovery of thieno[2,3-c]pyridines as potent COT inhibitors

Bioorg Med Chem Lett. 2008 Sep 15;18(18):4952-5. doi: 10.1016/j.bmcl.2008.08.037. Epub 2008 Aug 14.

Abstract

Evaluation of hit chemotypes from high throughput screening identified a novel series of 2,4-disubstituted thieno[2,3-c]pyridines as COT kinase inhibitors. Structural modifications exploring SAR at the 2- and 4-positions resulting in inhibitors with improved enzyme potency and cellular activity are disclosed.

MeSH terms

  • Combinatorial Chemistry Techniques
  • Crystallography, X-Ray
  • Humans
  • MAP Kinase Kinase Kinases / antagonists & inhibitors*
  • Models, Molecular*
  • Molecular Conformation
  • Molecular Structure
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis*
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*

Substances

  • Proto-Oncogene Proteins
  • Pyridines
  • Thiophenes
  • MAP Kinase Kinase Kinases
  • MAP3K8 protein, human