Synthesis of Novel Glutarimide Derivatives via the Interaction of α‐Methyleneglutarimide With Chlorohydrazones

ABSTRACT A convenient approach to the generation of two novel chemotypes of potential CRBN ligands via the interaction of α‐methyleneglutarimide with chlorohydrazone derivatives is described. The introduction of N ‐aryl substituted chlorohydrazones into the reaction leads to the formation of 1,2,7‐triazaspiro[4.5]dec‐2‐ene‐6,8‐diones with yields of 16%–76%. Conducting the synthesis with the participation of N ‐ Boc chlorohydrazones yields 3‐((2‐oxo‐1,3,4‐oxadiazol‐3(2 H )‐yl)methyl)piperidine‐2,6‐diones as products in 31%–65% yields. The synthesized compounds exhibit moderate cytotoxicity in in vitro assays against myeloma (MM1.S) and normal (PBMS) cell lines, supporting their safety profile as potential CRBN ligands.