4-Amino-6-piperazin-1-yl-pyrimidine-5-carbaldehyde oximes as potent FLT-3 inhibitors.
A series of 4-amino-6-piperazin-1-yl-pyrimidine-5-carbaldehyde oximes has been discovered and developed as potent FLT3 tyrosine kinase inhibitors. The series exhibited potent antiproliferative activity against both an FLT3 ITD-mutated human leukemic cell line as well as a wild-type FLT3 BaF(3) expressed cell line. The structure-activity relationship of this class of compounds is described.
Gaul
Micheal D
MD
Johnson and Johnson Pharmaceutical Research and Development LLC, Cranbury, NJ 08512, USA. mgaul@prdus.jnj.com
Xu
Guozhang
G
Kirkpatrick
Jennifer
J
Ott
Heidi
H
Baumann
Christian A
CA
D000447:Aldehydes / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009154:Mutation; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors*
D000447:Aldehydes; D010091:Oximes; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3