Synthesis and structure-activity relationship of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitriles as EGFR tyrosine kinase inhibitors

Madhavi Pannala; Sunil Kher; Norma Wilson; John Gaudette; Ila Sircar; Shao-Hui Zhang; Alexei Bakhirev; Guang Yang; Phoebe Yuen; Frank Gorcsan; Naoki Sakurai; Miguel Barbosa; Jie-Fei Cheng

doi:10.1016/j.bmcl.2007.07.071

Synthesis and structure-activity relationship of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitriles as EGFR tyrosine kinase inhibitors

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5978-82. doi: 10.1016/j.bmcl.2007.07.071. Epub 2007 Aug 21.

Authors

Madhavi Pannala¹, Sunil Kher, Norma Wilson, John Gaudette, Ila Sircar, Shao-Hui Zhang, Alexei Bakhirev, Guang Yang, Phoebe Yuen, Frank Gorcsan, Naoki Sakurai, Miguel Barbosa, Jie-Fei Cheng

Affiliation

¹ Department of Chemistry, Tanabe Research Laboratories USA, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.

PMID: 17827009
DOI: 10.1016/j.bmcl.2007.07.071

Abstract

Synthesis and structure-activity relationship of a series of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitrile derivatives as EGFR inhibitors is described. Compounds 29 and 30 showed potent in vitro inhibitory activity in the enzymatic assay as well as in the functional cellular assay. They are moderately selective against other types of tyrosine kinases.

MeSH terms

Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
ErbB Receptors / antagonists & inhibitors*
Nitriles / chemical synthesis
Nitriles / chemistry*
Nitriles / pharmacology*
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Nitriles
Quinolines
ErbB Receptors