Author/Authors :
Gaoquan Li، نويسنده , , Zhi-Fu Tao، نويسنده , , Yunsong Tong، نويسنده , , Magdalena K. Przytulinska، نويسنده , , Peter Kovar، نويسنده , , Philip Merta، نويسنده , , Zehan Chen، نويسنده , , Haiying Zhang، نويسنده , , Thomas Sowin، نويسنده , , Saul H. Rosenberg، نويسنده , , Nan-Horng Lin، نويسنده ,
Abstract :
A variety of macrocyclic urea compounds were prepared as potent Chk1 inhibitors by modifying the C5 position of the benzene ring of the macrocyclic urea with ether moieties, aliphatic carbon chains, amide and halides. Enzymatic activity less than 20 nM was observed in 29 of 40 compounds. Compounds 14, 46d, and 48j provided the best overall results in the cellular assays as they abrogated doxorubicin-induced cell cycle arrest (IC50 = 3.31, 3.08, and 3.13 μM) and enhanced doxorubicin cytotoxicity (IC50 = 0.54, 1.27, and 0.96 μM) while displaying no single agent activity, respectively.
