Novel <18>F marked 4-aminoquinazoline derivatives, and preparation methods and tumor PET development application thereof
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A technology of aminoquinazolines and quinazolines, which is applied in the field of new 18F-labeled 4-aminoquinazoline derivatives and its preparation and tumor PET imaging applications, which can solve the problem of poor stability in vivo and low tumor uptake , Poor water solubility, etc.
Inactive Publication Date: 2013-08-21
BEIJING NORMAL UNIVERSITY
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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.
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[0081] Prepared according to the following steps is R in formula A 1 =Br,R 2 =H compounds, including labeling precursors (R in formula B 1 =Br,R 1 =H compounds) organic synthesis and radiochemical synthesis of two parts.
[0082] 1) labeled precursor (R in formula B 1 =Br, R 2 = Compound of H)
[0083] 1.1 Synthesis of ethyl 3,4-dimethoxybenzoate
[0084] Add 3,4-dimethoxybenzoic acid (10g, 0.055mol) and ethanol (100mL) into a 250mL reaction flask, and slowly add concentrated sulfuric acid (8mL) dropwise under ice bath, heat up, and heat to reflux for 8-10h, TLC tracking monitoring, the reaction is complete, decompression spin off ethanol, add 100mL distilled water, use K 2 CO 3 The pH was adjusted to neutral, extracted with ethyl acetate, the organic layer was collected, and the solvent was spin-dried to obtain a pale yellow oil with a yield of 92%. 1 H-NMR (CDCl 3, 500MHz) δ (ppm): 7.65-7.67 (dd, 1H, Ar-H), 7.58-7.59 (d, 1H, Ar-H), 6.09-6.91 (d, 1H, Ar-H), 4.32-4.3...
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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 ...
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