title: Design and synthesis of tricyclic cores for kinase inhibition.
abstract: Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest.
authors.affiliation: Abbott Bioresearch Center, 381 Plantation St, Worcester, MA 01605, USA. stacy.vanepps@abbott.com
authors.forename: Stacy
authors.initials: S
authors.lastname: Van Epps
authors.forename: Bryan
authors.initials: B
authors.lastname: Fiamengo
authors.forename: Jeremy
authors.initials: J
authors.lastname: Edmunds
authors.forename: Anna
authors.initials: A
authors.lastname: Ericsson
authors.forename: Kristine
authors.initials: K
authors.lastname: Frank
authors.forename: Michael
authors.initials: M
authors.lastname: Friedman
authors.forename: Dawn
authors.initials: D
authors.lastname: George
authors.forename: Jonathan
authors.initials: J
authors.lastname: George
authors.forename: Eric
authors.initials: E
authors.lastname: Goedken
authors.forename: Brian
authors.initials: B
authors.lastname: Kotecki
authors.forename: Gloria
authors.initials: G
authors.lastname: Martinez
authors.forename: Philip
authors.initials: P
authors.lastname: Merta
authors.forename: Michael
authors.initials: M
authors.lastname: Morytko
authors.forename: Shashank
authors.initials: S
authors.lastname: Shekhar
authors.forename: Barbara
authors.initials: B
authors.lastname: Skinner
authors.forename: Kent
authors.initials: K
authors.lastname: Stewart
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Voss
authors.forename: Grier
authors.initials: G
authors.lastname: Wallace
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Neil
authors.initials: N
authors.lastname: Wishart
mesh_terms: D002478:Cells, Cultured; D003500:Cyclization; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011725:Pyridines; D011758:Pyrroles