Identification of 2-acylaminothiophene-3-carboxamides as potent inhibitors of FLT3

Raymond J Patch; Christian A Baumann; Jian Liu; Alan C Gibbs; Heidi Ott; Jennifer Lattanze; Mark R Player

doi:10.1016/j.bmcl.2006.03.032

Identification of 2-acylaminothiophene-3-carboxamides as potent inhibitors of FLT3

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3282-6. doi: 10.1016/j.bmcl.2006.03.032. Epub 2006 Mar 31.

Authors

Raymond J Patch¹, Christian A Baumann, Jian Liu, Alan C Gibbs, Heidi Ott, Jennifer Lattanze, Mark R Player

Affiliation

¹ Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA.

PMID: 16580199
DOI: 10.1016/j.bmcl.2006.03.032

Abstract

A series of 2-acylaminothiophene-3-carboxamides has been identified which exhibit potent inhibitory activity against the FLT3 tyrosine kinase. Compound 44 inhibits the isolated enzyme (IC50 = 0.027 microM) and blocks the proliferation of MV4-11 cells (IC50 = 0.41 microM). Structure-activity relationship studies within this series are described in the context of a proposed binding model within the ATP binding site of the enzyme.

MeSH terms

Amides / chemistry*
Amides / pharmacology*
Binding Sites
Cell Line
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*
Structure-Activity Relationship
Thiophenes / chemistry*
fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
fms-Like Tyrosine Kinase 3 / chemistry
fms-Like Tyrosine Kinase 3 / metabolism

Substances

Amides
Protein Kinase Inhibitors
Thiophenes
fms-Like Tyrosine Kinase 3