| The control of cell growth is mediated by a complex network of signaling pathways responsive to external influences, such as growth factors, as well as internal controls and checks. Epidermal growth factor (EGFR) was one of this kind of growth factors to be described, and was shown to be mitogenic, an effect mediated by the binding of EOF to a cell surface receptor(EGFR). So it becomes a new target of anti-cancer drugs. Subsequent investigations revealed EGFR to be one of the group of closely related receptors now referred to as the EGFR family, which includes EGFR, HER2, HER3 and HER4.These family members are considered to be important in the development, progression and aggressive behavior of human cancers.EGFR appears to play a critical role in both rumourigenesis and tumour growth, with its effects mediated by receptor overexpression, mutation of receptors with resulting constitutive activation or the presence of autocrine loops with resultant auto-stimulation. A number of excellent reviews regarding the relevance of EGFR as a target for anticancer therapies have been published recently. EGFR and its ligand have been shown to be overexpressed or to be involved in autocrine growth loops in a number of tumor types.The receptors exist as inactive monomers, which dimerize after ligand activation this causes homodimerization or heterodimerization between EGFR and another member of the erb receptor family. After ligand binding, the tyrosine kinase in tracelluar domain of the receptor is inactivated, with autophosphorylation of the intracellular domain, which initiates a cascade of intracellular events. The signaling pathway involves activates several nuclear proteins, including cyclin Dl, a protein required for cell cycle progression from Gl to S phase. EGFR signaling is not only critical for cell proliferation. Several studies have demonstrate that EGFR-mediated signals also contribute to other processes that are crucial to cancer progression, including angiogenesis, metastatic spread, and the inhibition of apoptosis.A variety of different approaches are currently being used to target the EGFR. The most promising strategies in clinical development include monoclonal antibodies to prevent ligand binding and small molecule inhibitors of the tyrosine kinase enzymatic activity to inhibit autophosphorylation and downstream intracellular signaling.Quinazoline compounds were prevalently discussed as a kind of small molecule inhibitors of the tyrosine kinase. And some compounds, such as PD153035, ZD1839, OSI774, were developed and are currently in clinical development.In order to study on more 4-aminoquinazoline compounds as selective epidermal growth factor receptor tyrosine kinase inhibitor, we have go along with the work as following two parts: 1 Synthesis section:Firstly, we synthesized five quinazoline compounds been reported to havebetter biological effect, and then we mainly took 2-amino-5-nitrobenitril as the original material, and it was under the reaction of six steps as hydrolysis, ring closing, halogenations, addition, reduction, and substitution in turn to get the ten quinazoline schifT bases, which have biological activities. Further, we determine the structure of each product by spectra data. 2 Biology sectionWe chose three kinds of cancer cell to check the biological activities of these 4-aniline quinazoline schiff bases. Moreover, a normal cell was selected for comparison to test their biology selectivity, and MTT methods were adopted. By all these, we had a better effect.Some innovative work we have done are listed as follows:(1) We improved on the hydrolysis condition of 2-amino, 5-nitrobenzioc acid. By compare the different hydrolysis result of different concentration under acid or base condition. On the common acid condition, the hydrosis of this compound will hardy happen. And while this reaction was placed on base medium, hydrolysis product will appear, and when the mol proportion of nitril to base is 1:1.5, the react yield is highest. The hydrolysis product w...
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