33987-02-9Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of conformationally constrained analogues of naphthol AS-E as inhibitors of CREB-mediated gene transcription
Jiang, Min,Li, Bingbing X.,Xie, Fuchun,Delaney, Frances,Xiao, Xiangshu
supporting information; experimental part, p. 4020 - 4024 (2012/07/16)
Cyclic AMP response element binding protein (CREB) is often dysregulated in cancer cells and is an attractive cancer drug target. Previously, we described naphthol AS-E (1) as a small molecule inhibitor of CREB-mediated gene transcription. To understand its bioactive conformation, a series of conformationally constrained analogues of 1 were designed and synthesized. Biological evaluation of these analogues suggests that the global energy minimum of 1 is the likely bioactive conformation.
Phenylamino-substituted tricyclic derivatives for treatment of hyperproliferative diseases
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Example 4, (2008/06/13)
The present invention relates to compounds of the formula (I) and to pharmaceutically acceptable salts thereof, wherein R1-R4and Z are as defined herein. The compounds of formula (I) are useful as antiproliferative agents. The invent
Tyrosine kinase inhibitors. 9. Synthesis and evaluation of fused tricyclic quinazoline analogues as ATP site inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor
Rewcastle, Gordon W.,Palmer, Brian D.,Bridges, Alexander J.,Showalter, H.D. Hollis,Sun, Li,Nelson, James,McMichael, Amy,Kraker, Alan J.,Fry, David W.,Denny, William A.
, p. 918 - 928 (2007/10/03)
Following the discovery of 4-[(3-bromophenyl)amino]-6,7- dimethoxyquinazoline (4; PD 153035) as an extremely patent (IC50 0.025 nM) inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), several fused tricyclic quinazoline analogues have been prepared and evaluated for their ability to inhibit the enzyme. The most potent compound was the linear imidazo[4,5-g]quinazoline (8), which exhibited an IC50 of 0.008 nM for inhibition of phosphorylation of a fragment of phospholipase C-γ1 as substrate. While N-methyl analogues of 8 showed similar potency, analogous N-[2-(dimethylamino)ethyl] derivatives were less effective. The next most potent compounds were the linear pyrazoloquinazolines (19 and 20) (IC50s 0.34 and 0.44 nM) and pyrroloquinazoline (21) (IC50 0.44 nM), while several other linear tricyclic ring systems of similar geometry to 8 (triazolo-, thiazolo-, and pyrazinoquinazolines) were less effective. In the imidazo[4,5-g]quinazoline and pyrroloquinazoline series, the corresponding angular isomers were also much less effective than the linear ones. These results are consistent with structure-activity relationship studies previously developed for the 4-[(3- bromophenyl)amino]quinazolines, which suggested that small electron-donating substituents at the 6- and 7-positions were desirable for high potency. Cellular studies of the linear imidazoloquinazoline 8 show that it can enter cells and rapidly and very selectively shut down EGF-stimulated signal transmission by binding competitively at the ATP site of the EGFR.
