title: Aminoimidazo[1,2-a]pyridines as a new structural class of cyclin-dependent kinase inhibitors. Part 1: Design, synthesis, and biological evaluation.
abstract: We have identified a novel structural class of protein serine/threonine kinase inhibitors comprised of an aminoimidazo[1,2-a]pyridine nucleus. Compounds from this family are shown to potently inhibit cyclin-dependent kinases by competing with ATP for binding to a catalytic subunit of the protein. Structure-based design approach was used to direct this chemical scaffold toward generating potent and selective CDK2 inhibitors. The discovery of this new class of ATP-site directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis of new medicinal chemistry tool in search for an effective treatment of cancer and other diseases that involve protein kinase signaling pathways.
authors.affiliation: Centro de Investigación Lilly, Avenida de la Industria, 30, 28108 Alcobendas, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Jaramillo
authors.forename: J Eugenio
authors.initials: JE
authors.lastname: de Diego
authors.forename: Chafiq
authors.initials: C
authors.lastname: Hamdouchi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Collins
authors.forename: Heather
authors.initials: H
authors.lastname: Keyser
authors.forename: Concha
authors.initials: C
authors.lastname: Sánchez-Martínez
authors.forename: Miriam
authors.initials: M
authors.lastname: del Prado
authors.forename: Bryan
authors.initials: B
authors.lastname: Norman
authors.forename: Harold B
authors.initials: HB
authors.lastname: Brooks
authors.forename: Scott A
authors.initials: SA
authors.lastname: Watkins
authors.forename: Charles D
authors.initials: CD
authors.lastname: Spencer
authors.forename: Jack Alan
authors.initials: JA
authors.lastname: Dempsey
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Anderson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Campbell
authors.forename: Tellie
authors.initials: T
authors.lastname: Leggett
authors.forename: Bharvin
authors.initials: B
authors.lastname: Patel
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
authors.forename: Juan
authors.initials: J
authors.lastname: Espinosa
authors.forename: Michal
authors.initials: M
authors.lastname: Vieth
authors.forename: Faming
authors.initials: F
authors.lastname: Zhang
authors.forename: David E
authors.initials: DE
authors.lastname: Timm
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D018844:Cyclin-Dependent Kinases