4-Amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones as potent ErbB-2/EGFR dual kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 16, 2008, Pages 4615-4619

  Xu, Guozhang ^a   Abad, Marta C ^a   Connolly, Peter J ^a   Neeper, Michael P ^a   Struble, Geoffrey T ^a   Springer, Barry A ^a   Emanuel, Stuart L ^a   Pandey, Niranjan ^a   Gruninger, Robert H ^a   Adams, Mary ^a   Moreno Mazza, Sandra ^a   Fuentes Pesquera, Angel R ^a   Middleton, Steven A ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Bioisostere; EGFR; ErbB 2; Hydrazones; Quinazoline; Receptor tyrosine kinase

Indexed keywords

4 AMINO 6 ARYLAMINO PYRIMIDINE 5 CARBALDEHYDE HYDRAZONE; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; HYDRAZONE DERIVATIVE; N,N DIMETHYLHYDRAZONE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CELL GROWTH; CELL PROLIFERATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAT; TUMOR CELL; X RAY CRYSTALLOGRAPHY;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; HUMANS; HYDRAZONES; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; MOLECULAR CONFORMATION; OXIMES; PROTEIN KINASE INHIBITORS; PYRIMIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 48649084335     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.07.020     Document Type: Article

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17. 50 values were calculated with standard deviation from two to eight separate experiments.
18. A sandwich ELISA was developed utilizing two mouse monoclonal antibodies in a 96-well format. SK-BR-3 cells were treated for 24 h with serial dilutions of test compound or vehicle, and cell lysates were prepared. Lysates were transferred to a capture plate coated with a primary antibody-specific for the human extracellular domain of the ErbB-2 receptor. A horseradish peroxidase-conjugated anti-phosphotyrosine secondary antibody was used to detect the extent of phosphorylation of the immobilized ErbB-2 receptor. The chromogenic substrate, tetra-methylbenzidine (TMB) was used to measure the absorbance on a spectrophotometer at 450 nm.
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