Design and synthesis of constrained analogs of LCRF-0004 as potent RON tyrosine kinase inhibitors

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.

Graphical abstractNew bicyclic lactam head groups as rigidified analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase were obtained.Figure optionsDownload full-size imageDownload as PowerPoint slide