Design and synthesis of novel 5, 6-bisindolylpyrimidin-4-ones structurally related to ruboxistaurin (LY333531)

2, 3-Bis(1-methyl-1H-indol-3-yl) methyl-3-oxopropionate is a key intermediate in the synthesis of a new family of LY333531 analogues. Base-mediated cyclocondensation with thiourea afforded novel 5, 6-bis(1-methyl-1H-indol-3-yl)-2-thioxo-2, 3-dihydropyrimidin-4(1H)-one, which was efficiently converted to the pyrimidin-2, 4(1H,3H)-dione congener. Synthesis of a six-membered K-252c analogue, 5, 6-bis(1-methyl-1H-indol-3-yl)pyrimidin- 4(3H)-one, is also described.