Parallel synthesis and biological evaluation of 5, 6, 7, 8-tetrahydrobenzothieno [2, 3-d] pyrimidin-4 (3H)-one cytotoxic agents selective for p21-deficient cells

…, M Miranda, CM Discafani, SK Rabindran

Index: Jennings, Lee D.; Kincaid, Scott L.; Wang, Yanong D.; Krishnamurthy, Girija; Beyer, Carl F.; McGinnis, John P.; Miranda, Miriam; Discafani, Carolyn M.; Rabindran, Sridhar K. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 21 p. 4731 - 4735

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Citation Number: 81

Abstract

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 ...