3-Cyano-6-(5-methyl-3-pyrazoloamino) pyridines (Part 2): A dual inhibitor of Aurora kinase and tubulin polymerization

Bioorganic & Medicinal Chemistry Letters
2016.0

Abstract

A new class of a dual inhibitor of Aurora kinase and tubulin polymerization was created by introducing various substituted phenoxyethylamino or pyridyloxyethylamino groups to the 2-position of 3-cyano-4-methyl-6-(5-methyl-3-pyrazoloamino)-pyridine. Compound 3g exhibited Aurora kinase inhibition, excellent protein kinase selectivity to Aurora kinase in comparison with 66 other kinases, inhibition of phosphorylation of Ser10 of histone H3 as an Aurora kinase inhibitor, inhibition of tubulin polymerization in vitro, good cell membrane permeability, and a good PK profile. Therefore compound 3g was effective in some antitumor mouse models at a dose of 30mg/kgpoqd.

Knowledge Graph

Similar Paper

3-Cyano-6-(5-methyl-3-pyrazoloamino) pyridines (Part 2): A dual inhibitor of Aurora kinase and tubulin polymerization
Bioorganic & Medicinal Chemistry Letters 2016.0
Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR
European Journal of Medicinal Chemistry 2018.0
Identification of novel inhibitors of Aurora A with a 3-(pyrrolopyridin-2-yl)indazole scaffold
Bioorganic & Medicinal Chemistry 2015.0
Single step synthesis of new fused pyrimidine derivatives and their evaluation as potent Aurora-A kinase inhibitors
European Journal of Medicinal Chemistry 2011.0
Discovery of Highly Potent and Selective Pan-Aurora Kinase Inhibitors with Enhanced in Vivo Antitumor Therapeutic Index
Journal of Medicinal Chemistry 2012.0
Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors
Bioorganic & Medicinal Chemistry Letters 2016.0
Discovery of 4-aminoquinazoline—urea derivatives as Aurora kinase inhibitors with antiproliferative activity
Bioorganic & Medicinal Chemistry 2014.0
6-Alkylamino- and 2,3-Dihydro-3‘-methoxy-2-phenyl-4-quinazolinones and Related Compounds:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization
Journal of Medicinal Chemistry 2000.0
N-Benzoylated Phenoxazines and Phenothiazines: Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization
Journal of Medicinal Chemistry 2011.0
Methyl 3-((6-Methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate (GN39482) as a Tubulin Polymerization Inhibitor Identified by MorphoBase and ChemProteoBase Profiling Methods
Journal of Medicinal Chemistry 2015.0