170449-18-0Relevant academic research and scientific papers
Design, synthesis, and DNA-binding of N-alkyl(anilino)quinazoline derivatives
Garofalo, Antonio,Goossens, Laurence,Baldeyrou, Brigitte,Lemoine, Amélie,Ravez, Séverine,Six, Perrine,David-Cordonnier, Marie-Hélène,Bonte, Jean-Paul,Depreux, Patrick,Lansiaux, Amélie,Goossens, Jean-Fran?ois
experimental part, p. 8089 - 8103 (2011/03/17)
New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared from 4-chloro-6,7-dimethoxyquinazoline 3, 4-chloro-6,7- methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a-c, 16a,b, and 17a,b), (aminophenyl)ureas (12a,b and 13a-f), anilines (4a-m, 20a,b), N-alkyl(aniline) (5a-m, 21a,b, 22a,d), and N-aminoalkyl(aniline) (22e-g) have been synthesized. These molecules were evaluated for their cytotoxic activities and as potential DNA intercalating agents. We studied the strength and mode of binding to DNA of these molecules by DNA melting temperature measurements, fluorescence emission, and circular dichroism. The results of various spectral and gel electrophoresis techniques obtained with the different compounds, in particular compounds 5g and 22f, revealed significant DNA interaction. These experiments confirm that the N-aminoalkyl(anilino)-6,7-dimethoxyquinazoline nucleus is an efficient pharmacophore to trigger binding to DNA, via an intercalative binding process.
Anilinodialkoxyquinazolines: Screening epidermal growth factor receptor tyrosine kinase inhibitors for potential tumor imaging probes
VanBrocklin, Henry F.,Lim, John K.,Coffing, Stephanie L.,Hom, Darren L.,Negash, Kitaw,Ono, Michele Y.,Gilmore, Jennifer L.,Bryant, Ianthe,Riese II, David J.
, p. 7445 - 7456 (2007/10/03)
The epidermal growth factor receptor (EGFR), a long-standing drug development target, is also a desirable target for imaging. Sixteen dialkoxyquinazoline analogues, suitable for labeling with positron-emitting isotopes, have been synthesized and evaluated in a battery of in vitro assays to ascertain their chemical and biological properties. These characteristics provided the basis for the adoption of a selection schema to identify lead molecules for labeling and in vivo evaluation. A new EGFR tyrosine kinase radiometric binding assay revealed that all of the compounds possessed suitable affinity (IC50 = 0.4-51 nM) for the EGFR tyrosine kinase. All of the analogues inhibited ligand-induced EGFR tyrosine phosphorylation (IC 50 = 0.8-20 nM). The HPLC-estimated octanol/water partition coefficients ranged from 2 to 5.5. Four compounds, 4-(2′-fluoroanilino)- and 4-(3′-fluoroanilino)-6,7-diethoxyquinazoline as well as 4-(3′-chloroanilino)- and 4-(3′-bromoanilino)-6,7- dimethoxyquinazoline, possess the best combination of characteristics that warrant radioisotope labeling and further evaluation in tumor-bearing mice.
COMPOUNDS DERIVED FROM 4--ANILINEQUINAZOLINES WITH ADENOSINE-KIASE INHIBITOR PROPERTIES
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Page/Page column 22-23, (2008/06/13)
The present invention introduces compounds that are adenosine-kinase inhibitors. We provide a process of protecting tissues and organs like heart, brain and kidneys affected by ischemia, and of treating heart insufficiency, myocardium infarct, arrhythmia, arterial hypertension, atherosclerosis, coronary artery re-stenosis after angioplasty, chronic renal insufficiency, cerebral vascular accident, and chronic inflammatory diseases (e.g. rheumatoid arthritis). We also provide the adenosine-kinase inhibitor effect of compounds derived from quinazolines, which were previously known as reversible inhibitors of tyrosine-kinases from the family of epidermic growth factor receptors (EGFR).
Syntheses of Some 4-Anilinoquinazoline Derivatives
Rocco, Silvana A.,Barbarini, Jose Eduardo,Rittner, Roberto
, p. 429 - 435 (2007/10/03)
Some 4-N-(3′- or 4′-substituted-phenyl)amino-6,7- dimethoxyquinazolines and the corresponding unsubstituted compounds were synthesized from 2-amino-4,5-dimethoxybenzoic acid and the appropriate substituted anilines. Other related quinazolines or their synthetic intermediates were also obtained. A large number of the described quinazolines are new compounds, while the remaining were prepared by a more efficient procedure. The main goal for the synthesis of these compounds comes from the fact that the 4-anilinoquinazoline pharmacophore is an important unit, which is found among the ATP-competitive inhibitors of several protein kinase enzymes.
The preparation and SAR of 4-(anilino), 4-(phenoxy), and 4-(thiophenoxy)-quinazolines: Inhibitors of p56(lck) and EGF-R tyorsine kinase activity
Myers, Michael R.,Setzer, Natalie N.,Spada, Alfred P.,Zulli, Allison L.,Hsu, Chin-Yi J.,Zilberstein, Asher,Johnson, Susan E.,Hook, Linda E.,Jacoski, Mary V.
, p. 417 - 420 (2007/10/03)
We report herein our preliminary results of a SAR study of quinazoline-based inhibitors of p56(lck) and EGF-R tyrosine kinase activity. The most potent inhibitor of p56(lck) identified, RPR-108518A (10), has an IC50 of 0.50 μM. The 3-chlorophenoxy- and 3-chlorothiophenoxy- derivatives 5 and 6 were also shown to be extremely potent EGF-R inhibitors.
Tyrphostins IV - Highly potent inhibitors of EGF receptor kinase. Structure-activity relationship study of 4-anilidoquinazolines
Gazit, Aviv,Chen, Jeffrey,Harald, App,McMahon, Gerald,Hirth, Peter,Chen, Irit,Levitzki, Alexander
, p. 1203 - 1207 (2007/10/03)
Potent 4-anilido-substituted quinazolines which potently inhibit epidermal growth factor receptor (EGFR) kinase were prepared. Structure-activity relationship studies reveal high sensitivity to substitution at the aniline ring.
