title: Large-scale synthesis of GMP grade alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13), a new anti-cancer drug candidate.
abstract: The leflunomide (CAS 75706-12-6) metabolite (LFM) analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13, DDE-28, CAS 244240-24-2), is a rationally designed inhibitor of the anti-apoptotic enzyme Bruton's tyrosine kinase (BTK). LFM-A13 is being developed as a novel dual-function anticancer drug with apoptosis-promoting and anti-thrombotic properties. LFM-A13 was prepared under current Good Manufacturing Practice (cGMP) conditions on the scale of kilograms.
authors.affiliation: Paradigm Pharmaceuticals, 2139 Fourth Street, White Bear Lake, MN 55110, USA.
authors.forename: Darin
authors.initials: D
authors.lastname: DuMez
authors.forename: Taracad K
authors.initials: TK
authors.lastname: Venkatachalam
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000577:Amides / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004339:Drug Compounding / Q000592:standards; D004340:Drug Contamination; D004345:Drug Industry / Q000592:standards; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019216:Metals, Heavy / Q000032:analysis; D009570:Nitriles / Q000138:chemical synthesis*; D010316:Particle Size; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000032:analysis
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; C118451:LFM A13; D019216:Metals, Heavy; D009570:Nitriles; D014867:Water