title: Identification of a Novel Series of Potent TrkA Receptor Tyrosine Kinase Inhibitors.
abstract: A novel series of N-(3-(6-substituted-aminopyridin-3-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting TrkA receptor tyrosine kinase was identified. SAR study of the series allowed us to design and synthesize compounds possessing inhibitory activity of TrkA kinase enzyme in the low nanomolar range with low residual activity against c-Met and with no significant activity against VEGFR2.
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: Stéphane L
authors.initials: SL
authors.lastname: Raeppel
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gaudette
authors.affiliation: Department of Cell Biology and Pharmacology, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: Hannah
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Department of Cell Biology and Pharmacology, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: Normand
authors.initials: N
authors.lastname: Beaulieu
authors.affiliation: Department of PK/Analytical Chemistry, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: James
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Pharmacology, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: Christiane
authors.initials: C
authors.lastname: Maroun
authors.affiliation: Department of Cell Biology and Pharmacology, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc., 7150 Rue Frederick-Banting, Suite 200, Montréal, QC, Canada H4S 2A1.
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg