title: Design and synthesis of constrained analogs of LCRF-0004 as potent RON tyrosine kinase inhibitors.
abstract: New fused bicyclic lactam head groups as rigidified analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Depending on the functionalities and the size of these bicyclic head groups, potent inhibitors of RON tyrosine kinase with various level of selectivity against c-Met tyrosine kinase were obtained.
authors.affiliation: Laboratoires ChemRF Inc. / ChemRF Laboratories Inc., 3194 rue Claude-Jodoin, Montréal, QC H1Y 3M2, Canada. Electronic address: stephane.raeppel@gmail.com.
authors.forename: Stéphane L
authors.initials: SL
authors.lastname: Raeppel
authors.affiliation: Laboratoires ChemRF Inc. / ChemRF Laboratories Inc., 3194 rue Claude-Jodoin, Montréal, QC H1Y 3M2, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Therrien
authors.affiliation: Laboratoires ChemRF Inc. / ChemRF Laboratories Inc., 3194 rue Claude-Jodoin, Montréal, QC H1Y 3M2, Canada.
authors.forename: Franck
authors.initials: F
authors.lastname: Raeppel
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000737:chemistry; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D006574:Heterocyclic Compounds, 2-Ring; C000605132:LCRF-0004; D007769:Lactams; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D019859:Proto-Oncogene Proteins c-met; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases
keywords: Bicyclic head group; Homology model; Molecular docking; RON; RTK inhibitors; c-Met