title: Potent 2'-aminoanilide inhibitors of cFMS as potential anti-inflammatory agents.
abstract: A series of 2'-aminoanilides have been identified which exhibit potent and selective inhibitory activity against the cFMS tyrosine kinase. Initial SAR studies within this series are described which examine aroyl and amino group substitutions, as well as the introduction of hydrophilic substituents on the benzene core. Compound 47 inhibits the isolated enzyme (IC(50)=0.027 microM) and blocks CSF-1-induced proliferation of bone marrow-derived macrophages (IC(50)=0.11 microM) and as such, serves as a lead candidate for further optimization studies.
authors: Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA.
authors: Raymond J
authors: RJ
authors: Patch
authors: Benjamin M
authors: BM
authors: Brandt
authors: Davoud
authors: D
authors: Asgari
authors: Nand
authors: N
authors: Baindur
authors: Naresh K
authors: NK
authors: Chadha
authors: Taxiarchis
authors: T
authors: Georgiadis
authors: Wing S
authors: WS
authors: Cheung
authors: Ioanna P
authors: IP
authors: Petrounia
authors: Robert R
authors: RR
authors: Donatelli
authors: Margery A
authors: MA
authors: Chaikin
authors: Mark R
authors: MR
authors: Player
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000813:Anilides; D000893:Anti-Inflammatory Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D016186:Receptor, Macrophage Colony-Stimulating Factor