잠재적 COX-2 억제작용이 있는 1,5-Diarylhydantoin 유도체의 합성

Synthesis of Potential COX-2 Inhibitory 1,5-Diarylhydantoin Derivatives

Fer the development of new COX-2 inhibitors, 1,5-diarylhydantoins 5a-5c and 1,5- diaryl-2-thiohydantoin 6a-6c were synthesized from commercially available phenylacetic acids through esterifcation, bromination, C-N bond formation and cyclization. Esters 2a-c were efficiently synthesized from the starting materials la- c by reflux(ins in absolute methanol for 3 hours with catalytic concentrated sulfuric acid. Bromination of 2a-c was carried out with use of N-bomo-succinimide at rt in dichloromethane. The bromine of 3a~c was substituted with aniline in ethanol or N,N- dimethylformamide to provide 4a~c. Hydantoins and 2-thiohydantoins were synthesized from 4a~c by treatment of potassium isocyanate or potassium thiocyanate in dil- ethanol with triethylamine.