Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1379386 | Bioorganic & Medicinal Chemistry Letters | 2005 | 5 Pages |
A novel series of inhibitors of cancer cell proliferation, selective against p21 cell cycle checkpoint-disrupted cells vs. cells with intact p21 checkpoint, were identified by high-throughput screening. Optimization of both ends of the lead molecule to improve potency, using parallel synthesis and iterative design, is described. The 2-(1,4-dibenzodioxane)-substituted derivative 14 was identified as a highly selective and potent agent displaying an IC50 of 91 nM in the p21-deficient cell line.
Graphical abstractA novel series of anti-proliferative agents containing the thieno[2,3-d]pyrimidin-4-one scaffold and the structure–activity relationship studies to improve potency is described.Figure optionsDownload full-size imageDownload as PowerPoint slide