128772-82-7

Upstream product

• 105-07-7 4-cyanobenzaldehyde 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 43038-36-4 4-cyanobenzohydrazide 
• 1422157-66-1 N′-[chloro-(4-cyanophenyl)methylene]-tert-butylcarbazate 
• 149267-91-4 tert-butyl-2-(4-cyanobenzylidene)hydrazinecarboxylate 
• 99502-89-3 Chlorameisensaeure-N-hydroxy-norborn-5-en-2,3-dicarboximidester 

Relevant academic research and scientific papers

5-Phenyl-1,3,4-oxadiazol-2(3 H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit

Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-Triazole 7 as an attractive starting point for a structure-based drug design hit-To-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with drug-like chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling.

Synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones from N′-(chloro-aryl- methylene)-tert-butylcarbazates using basic alumina as an efficient and recyclable surface under solvent-free condition

The synthesis of biologically important 5-aryl-3H-[1,3,4]oxadiazol-2-ones has been carried out by heating the easily synthesized N′-(chloro-aryl- methylene)-tert-butylcarbazates on basic alumina surface under solvent-free condition. The dual characteristic of basic alumina as a solid support as well as a nucleophile is successfully exploited in these reactions. The method provides special attributions such as reduced reaction times, easier work-up procedures, and good to excellent yields as well as increased purity of products and most importantly environmentally friendly protocols. The basic alumina is easily recovered and utilized for further reactions several times without serious loss of activity.