- 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
-
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.
- 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.
-
p. 4731 - 4735
(2007/10/03)
-
- Synthesis and bioactivities of novel bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridines as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production.
-
We synthesized bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives, and evaluated for their ability to inhibit LPS-stimulated production of TNF-alpha. Several compounds revealed excellent in vivo activity. Furthermore, an effective compound was found in adjuvant-induced arthritic model (AIA) of rat.
- Fujita, Masakazu,Seki, Taketsugu,Ikeda, Naoko
-
p. 1897 - 1900
(2007/10/03)
-