169205-86-1Relevant academic research and scientific papers
Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors
Hu, Shaojing,Xie, Guojian,Zhang, Don X.,Davis, Charles,Long, Wei,Hu, Yunyan,Wang, Fei,Kang, Xinshan,Tan, Fenlai,Ding, Lieming,Wang, Yinxiang
, p. 6301 - 6305 (2012/10/29)
Crown ether fused anilinoquinazoline analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities in an in vitro EGFR kinase assay a
Rapid microwave-assisted cleavage of methyl phenyl ethers: New method for synthesizing desmethyl precursors and for removing protecting groups
Fredriksson, Anna,Stone-Elander, Sharon
, p. 529 - 538 (2007/10/03)
A new microwave-enhanced method for rapid demethylation of methyl phenyl ethers using neat methanesulfonic acid (CH3SO3H) is presented. Using a monomodal microwave cavity, cleavage of anisole (1), used as model compound, to phenol (2) was achieved with high conversions (ca 80%) in very short reaction times (10-20 s). The feasibility of cleaving one or both of two methoxy groups was illustrated with 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD153035, 3). High conversions (≥82%) of 3 were attained with four different conditions (i.e. combination of input effect (35-125 W) and time (15s-2min)). 4-(3-Bromoanilino)-7-hydroxy-6-methoxyquinazoline (4), 4-(3-bromoanilino)-6-hydroxy-7-methoxyquinazoline (5) and 4-(3-bromoanilino)-6,7-dihydroxyquinazoline (6), the possible mono- or di-demethylated compounds, were obtained. Methods for rapid demethylations are of interest in radiochemistry for post-labeling deprotections of hydroxyl containing aromatic rings and also provide a more direct route for synthesizing precursor compounds for labeling by alkylation. Copyright
Tyrosine kinase inhibitors. 5. Synthesis and structure-activity relationships for 4-[(phenylmethyl)amino]- and 4-(phenylamino)quinazolines as potent adenosine 5'-triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth factor receptor
Rewcastle,Denny,Bridges,Zhou,Cody,McMichael,Fry
, p. 3482 - 3487 (2007/10/02)
A series of 4-substituted quinazolines and related compounds have been prepared and evaluated for their ability to inhibit the tyrosine kinase activity of the epidermal growth factor receptor on a phospholipase C-γ1- derived substrate. The results show a narrow structure-activity relationship (SAR) for the basic ring system, with quinazoline being the preferred chromophore and benzylamino and anilino the preferred side chains. In the 4- anilino series, substitution on the 3-position of the phenyl ring with small lipophilic electron-withdrawing groups provided analogues with enhanced potency. Two series of compounds [4-(phenylmethyl)amino and 4-(3- bromophenyl)amino] were studied to determine SARs for quinazoline substituents. In the more active 4-(3-bromophenyl)amino series, electron- donating groups (NH2, OMe) at the 6- or 7-position increased activity, in a pattern consistent with a requirement for high electron density in the vicinity of the 8-position of the quinazoline ring. The 6,7-dimethoxy derivatives were the most effective in both series, with the 4-(3- bromophenyl)amino derivative (3) having an IC50 of 0.029 nM, making it by far the most potent reported inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor enzyme.
