title: Discovery of novel imidazo[1,2-a]pyridines as inhibitors of the insulin-like growth factor-1 receptor tyrosine kinase.
abstract: We disclose a novel series of insulin-like growth factor-1 receptor kinase inhibitors based on the 3-(pyrimidin-4-yl)-imidazo[1,2-a]pyridine scaffold. The influence on the inhibitory activity of substitution on the imidazopyridine and at the C5 position of the pyrimidine is discussed. In the course of this optimization, we discovered a potent and selective inhibitor with suitable pharmacokinetics for oral administration.
authors.affiliation: AstraZeneca, Oncology Innovative Medicines, Centre de Recherches, Z.I. Pompelle, 51689 Reims Cedex 2, France. richard.ducray@astrazeneca.com
authors.forename: Richard
authors.initials: R
authors.lastname: Ducray
authors.forename: Iain
authors.initials: I
authors.lastname: Simpson
authors.forename: Frederic H
authors.initials: FH
authors.lastname: Jung
authors.forename: J Willem M
authors.initials: JW
authors.lastname: Nissink
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kenny
authors.forename: Martina
authors.initials: M
authors.lastname: Fitzek
authors.forename: Graeme E
authors.initials: GE
authors.lastname: Walker
authors.forename: Lara T
authors.initials: LT
authors.lastname: Ward
authors.forename: Kevin
authors.initials: K
authors.lastname: Hudson
mesh_terms: D000818:Animals; D004285:Dogs; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017526:Receptor, IGF Type 1; C001439:imidazo(1,2-a)pyridine