Structure-based design and synthesis of pyrrole derivatives as MEK inhibitors

Michael B Wallace; Mark E Adams; Toufike Kanouni; Clifford D Mol; Douglas R Dougan; Victoria A Feher; Shawn M O'Connell; Lihong Shi; Petro Halkowycz; Qing Dong

doi:10.1016/j.bmcl.2010.05.058

Structure-based design and synthesis of pyrrole derivatives as MEK inhibitors

Bioorg Med Chem Lett. 2010 Jul 15;20(14):4156-8. doi: 10.1016/j.bmcl.2010.05.058. Epub 2010 May 20.

Authors

Michael B Wallace¹, Mark E Adams, Toufike Kanouni, Clifford D Mol, Douglas R Dougan, Victoria A Feher, Shawn M O'Connell, Lihong Shi, Petro Halkowycz, Qing Dong

Affiliation

¹ Takeda San Diego, 10410 Science Center Drive, San Diego, CA 92121, United States. [email protected]

PMID: 20621728
DOI: 10.1016/j.bmcl.2010.05.058

Abstract

A novel series of pyrrole inhibitors of MEK kinase has been developed using structure-based drug design. Optimization of the series led to the identification of potent inhibitors with good pharmaceutical properties.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Crystallography, X-Ray
Drug Design
MAP Kinase Kinase Kinases / antagonists & inhibitors*
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Pyrroles / chemical synthesis
Pyrroles / chemistry*
Pyrroles / pharmacology
Rats

Substances

Protein Kinase Inhibitors
Pyrroles
MAP Kinase Kinase Kinases