Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors

Research trends in pharmacological modulation of tumor‐associated macrophages

“…To date, it has been reported that 58 kinds of RTKs are edited by the human genome 117,118 . Notably, colony stimulation factor‐1 receptor (CSF‐1R), one of the most important members of the RTKs family, is highly expressed by TAMs 119 . Upon binding to its ligands including CSF‐1 or IL‐34, CSF‐1R undergoes dimerization and therefore causes a signaling cascade that facilitates the proliferation, functioning, and survival of macrophages.…”

Conformational restriction of a type II FMS inhibitor leading to discovery of 5-methyl-N-(2-aryl-1H-benzo[d]imidazo-5-yl)isoxazole-4-carboxamide analogues as selective FLT3 inhibitors

“…Kinase profiling according to chemical scaffold. The profiles of the FMS kinase inhibitor 13 and benzimidazole derivative 5a (10 μM) are shown.…”

“…Type II FMS inhibitors consist of three parts, a hydrogen-bonding hinge, a central phenyl ring, and a secondary hydrophobic aromatic ring that facilitates binding to the DFG pocket 13 . Amide or urea linkages connect the middle phenyl ring and secondary hydrophobic aromatic ring.…”

The synthetic and therapeutic expedition of isoxazole and its analogs

“…SAR studies revealed that an electron-rich fused ring (R) at the phenyl was beneficial for the antiproliferative activity. Im et al (2015) synthesized a series of 4arylamido 3-methylisoxazoles and evaluated them for antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Most of the compounds displayed selective antiproliferative activity toward the U937 cell line, and the activities were better than the reference drug Sorafenib while weak cytotoxic activities against human normal cell line and A375P.…”