title: Discovery of new quinoline ether inhibitors with high affinity and selectivity for PDGFR tyrosine kinases.
abstract: A new series of quinoline ether inhibitors, which potently and selectively inhibit PDGFR tyrosine kinases, is described in this Letter. Compounds 23 and 33 are selective, low nanomolar inhibitors of PDGFRα and β, display good pharmacokinetics in rat and dog and are active in vivo at low doses when given orally twice daily. Further evaluation of these compounds is warranted.
authors.affiliation: AstraZeneca, Centre de Recherches, BP 1050, 51689 Reims Cedex 2, France. patrick.ple@astrazeneca.com
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Plé
authors.forename: Frédéric
authors.initials: F
authors.lastname: Jung
authors.forename: Sue
authors.initials: S
authors.lastname: Ashton
authors.forename: Laurent
authors.initials: L
authors.lastname: Hennequin
authors.forename: Romuald
authors.initials: R
authors.lastname: Laine
authors.forename: Christine
authors.initials: C
authors.lastname: Lambert-van der Brempt
authors.forename: Rémy
authors.initials: R
authors.lastname: Morgentin
authors.forename: Georges
authors.initials: G
authors.lastname: Pasquet
authors.forename: Sian
authors.initials: S
authors.lastname: Taylor
mesh_terms: D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004987:Ethers / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*
chemical_list: D004987:Ethers; D011804:Quinolines; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor