Identification of 2-acylaminothiophene-3-carboxamides as potent inhibitors of FLT3.
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.
Patch
Raymond J
RJ
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA.
Baumann
Christian A
CA
Liu
Jian
J
Gibbs
Alan C
AC
Ott
Heidi
H
Lattanze
Jennifer
J
Player
Mark R
MR
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry*; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000577:Amides; D047428:Protein Kinase Inhibitors; D013876:Thiophenes; D051941:fms-Like Tyrosine Kinase 3