title: Reducing ion channel activity in a series of 4-heterocyclic arylamide FMS inhibitors.
abstract: During efforts to improve the bioavailability of FMS kinase inhibitors 1 and 2, a series of saturated and aromatic 4-heterocycles of reduced basicity were prepared and evaluated in an attempt to also improve the cardiovascular safety profile over lead arylamide 1, which possessed ion channel activity. The resultant compounds retained excellent potency and exhibited diminished ion channel activity.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Spring House, PA 19477, USA. kwilso10@its.jnj.com
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Wilson
authors.forename: Carl R
authors.initials: CR
authors.lastname: Illig
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Chen
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Wall
authors.forename: Shelley K
authors.initials: SK
authors.lastname: Ballentine
authors.forename: Renee L
authors.initials: RL
authors.lastname: DesJarlais
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Chen
authors.forename: Carsten
authors.initials: C
authors.lastname: Schubert
authors.forename: Robert
authors.initials: R
authors.lastname: Donatelli
authors.forename: Ioanna
authors.initials: I
authors.lastname: Petrounia
authors.forename: Carl S
authors.initials: CS
authors.lastname: Crysler
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Molloy
authors.forename: Margery A
authors.initials: MA
authors.lastname: Chaikin
authors.forename: Carl L
authors.initials: CL
authors.lastname: Manthey
authors.forename: Mark R
authors.initials: MR
authors.lastname: Player
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Tomczuk
authors.forename: Sanath K
authors.initials: SK
authors.lastname: Meegalla
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D006571:Heterocyclic Compounds; D047428:Protein Kinase Inhibitors; D016186:Receptor, Macrophage Colony-Stimulating Factor