Structure-activity relationship study of novel tissue transglutaminase inhibitors.

Research paper by Eric E Duval, April A Case, Ross L RL Stein, Gregory D GD Cuny

Indexed on: 23 Mar '05Published on: 23 Mar '05Published in: Bioorganic & Medicinal Chemistry Letters


Thieno[2,3-d]pyrimidin-4-one acylhydrazide derivatives were discovered as moderately potent inhibitors of TGase 2 (tissue transglutaminase) utilizing a fluorescence-based assay that measured TGase 2 catalyzed incorporation of the dansylated Lys derivative alpha-N-Boc-Lys-CH(2)-CH(2)-dansyl into the protein substrate N,N-dimethylated-casein. A SAR study revealed that the acylhydrazide thioether side-chain and the thiophene ring were critical to inhibitory activity.