Structure–activity relationship study of novel tissue transglutaminase inhibitors

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 α-N-Boc-Lys-CH2-CH2-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.