Preparation method and application of a class of aniline quinazoline compounds

Abstract

The invention provides a class of aniline quinazoline compounds, namely quinazoline-4-aniline-2-(N,N,N-trialkyl) quaternary ammonium salt derivatives, which are radiochemically synthesized into 2-fluoro-18 The substituted derivatives, as precursors of fluorine-18 labeling, can be used in the preparation of tumor positron imaging agents. The imaging agent targets epidermal growth factor and can perform specific tumor imaging. The preparation method of the derivative of the present invention has the following advantages: the synthesis steps are simple, and only one step of fluorine-18 labeling the quaternary ammonium salt precursor is required to obtain the target compound; the radiochemical synthesis time is fast, and only needs 20-25 minutes; the separation is simple and convenient, and HPLC separation is not required , a Sep-Pak C-18 column can be used to obtain a product with a radiochemical purity of more than 98%, while removing the quaternary ammonium salt precursor; the radiochemical yield is high, and the uncorrected yield can reach 40-60%. High specific activity of radioactivity. The general structural formula is: .

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a class of aniline quinazoline compounds and their preparation method and application. This class of compounds can be used to radiochemically synthesize a class of positron imaging agents for tumor imaging. Background technique [0002] Quinazolines are a class of important heterocyclic compounds with a wide range of uses and high biological activity, mainly for EGFR or its tyrosine kinase (EGFR-TK), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth The inhibitory activity of PDGFR, Nerve Growth Factor Receptor (NGFR) and other multiple targets, thus exerting various pharmacological effects such as anticancer, antibacterial, antiviral, etc. In particular, 4-aniline quinazoline compounds are the most active and selective tyrosine kinase inhibitors discovered so far, and the main target of this type of compounds is EGFR. There are several anilinoquina...

AI Technical Summary

Problems solved by technology

It has been reported that PD153035 labeled with positron nuclide 11C, F-18, gefitinib, erlotinib, etc. are used as new PET imaging agents for tumor imaging , however, because the half-life of 11C (t1 / 2=20.4 minutes) is too short, it can only be used in PET centers with accelerators for producing positron nuclides, and cannot distribution, and the yield is very low, and the production can only meet the inspection needs of one patient at a time, which greatly limits the use of these imaging agents, and F-18-labeled drugs, the labeling steps are cumbersome, and the labeling time is too long, so it is not suitable for Clinical promotion, the present invention has synthesized a new class of aniline quinazoline compounds, which can be used to radiochemically synthesize 2-position F-18 labeled aniline quinazoline positron drugs for tumor imaging. Phenyl compounds are used as labeling precursors, the labeling method is simple and the labeling yield is high

Images