Title of article :
Both 5-arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones and 3-thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-ones are light-Dependent tumor necrosis factor-α antagonists
Author/Authors :
Matthew E. Voss، نويسنده , , Percy H. Carter، نويسنده , , Andrew J. Tebben، نويسنده , , Peggy A. Scherle، نويسنده , , Gregory D. Brown، نويسنده , , Lorin A. Thompson، نويسنده , , Meizhong Xu، نويسنده , , Yvonne C. Lo، نويسنده , , Gengjie Yang، نويسنده , , Ruiqin Liu، نويسنده , , Paul Strzemienski، نويسنده , , J. Gerry Everlof، نويسنده , , James M. Trzaskos، نويسنده , , Carl P. Decicco، نويسنده ,
Abstract :
Based on the realization that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones are tumor necrosis factor-α antagonists, we discovered two additional classes of antagonists: 3-thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-ones (via rational design) and 5-arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones (via computer-guided screening). Chemical modification of the lead structures showed that the structure–activity relationship profiles for both of these series were dependent on the electronic properties of the molecules. Subsequent studies showed that they were light-dependent inhibitors.
