Novel <18>F marked 4-aminoquinazoline derivatives, and preparation methods and tumor PET development application thereof

Abstract

The invention provides novel <18>F marked 4-aminoquinazoline compounds. The novel <18>F marked 4-aminoquinazoline compounds are characterized in that one end of each of the novel <18>F marked 4-aminoquinazoline compounds has a <18>F substituted alkyloxy structure; the other end of each of the compounds has a 6,7-substituted quinazoline structure, and a substituent R1 is positioned in the 3 position of a 4-aminobenzene ring which is the quinazoline maternal, and is H, F, Cl, Br, I, a trifluoromethyl group or an acetenyl group; a substituent R2 is positioned in the 4 position of the 4-aminobenzene ring which is the quinazoline maternal, and is H, F, Cl, Br, a methyl group, a methoxy group, a 3-fluorophenoxyl group, or a 2-pyridyloxy group; and n is 1-5. The structural formula of the compounds is shown as A in the specification. Results of experiments show that the precursor of the marker of the compounds is easy to synthesize, marks through using a two-step method and has a high marking rate. The compounds have a good bioactivity, for example, the compounds have high absorption and slow removal in tumor tissues and low intake and fast removal in normal tissues and blood, so the compounds have a high tumor / background ratio, and especially have a high tumor / blood ratio, a high tumor / flesh ratio and a high tumor / brain ration, are in favor of the PET tumor development, and perform a huge potential as a brain tumor developer.

Description

Technical field: [0001] The present invention relates to a new 18 F-labeled 4-aminoquinazoline derivatives, their chemical preparation method and their application as tumor imaging agents for positron emission tomography (PET). Background technique: [0002] Positron emission tomography (Positron emission tomography) PET is a functional imaging method that can quantitatively and dynamically observe the physiological and biochemical changes of drugs or metabolites in the human body from the molecular level without damage in vitro. It is a technology for functional, metabolic and receptor imaging with high sensitivity and specificity. [0003] Among the radionuclides commonly used in PET imaging, 18 F has a long half-life (t 1 / 2 =109.8min), and has a lower radiation dose and a shorter range to the tissue, and its hydrogen-like properties will not cause significant changes in the spatial structure of the labeled molecules, so these excellent properties make 18 F has become ...

AI Technical Summary

Problems solved by technology

However, these reported radiolabeled imaging agents have some disadvantages, such as poor water solubility, low tumor uptake, and poor stability in vivo, which greatly restricts their further application.

Images