20323-74-4Relevant articles and documents
Overcoming the Deallylation Problem: Palladium(II)-Catalyzed Chemo-, Regio-, and Stereoselective Allylic Oxidation of Aryl Allyl Ether, Amine, and Amino Acids
Begam, Hasina Mamataj,Jana, Ranjan,Manna, Kartic,Samanta, Krishanu
supporting information, p. 7443 - 7449 (2020/10/09)
We report herein a Pd(II)/bis-sulfoxide-catalyzed intramolecular allylic C-H acetoxylation of aryl allyl ether, amine, and amino acids with the retention of a labile allyl moiety. Mechanistically, the reaction proceeds through a distinct double-bond isomerization from the allylic to the vinylic position followed by intramolecular carboxypalladation and the β-hydride elimination pathway. For the first time, C-H oxidation of N-allyl-protected amino acids to furnish five-membered heterocycles through 1,3-syn-addition is established with excellent diastereoselectivity.
Synthesis and evaluation of novel 18F-labeled quinazoline derivatives with low lipophilicity for tumor PET imaging
Chong, Yan,Chang, Jin,Zhao, Wenwen,He, Yong,Li, Yuqiao,Zhang, Huabei,Qi, Chuanmin
, p. 42 - 53 (2018/02/06)
Four novel 18F-labeled quinazoline derivatives with low lipophilicity, [18F]4-(2-fluoroethoxy)-6,7-dimethoxyquinazoline ([18F]I), [18F]4-(3-((4-(2-fluoroethoxy)-7-methoxyquinazolin-6-yl)oxy)propyl)morpholine ([18F]II), [18F]4-(2-fluoroethoxy)-7-methoxy-6-(2-methoxyethoxy)quinazoline ([18F]III), and [18F]4-(2-fluoroethoxy)-6,7-bis(2-methoxyethoxy)quinazoline ([18F]IV), were synthesized via a 2-step radiosynthesis procedure with an overall radiochemical yield of 10% to 38% (without decay correction) and radiochemical purities of >98%. The lipophilicity and stability of labeled compounds were tested in vitro. The log P values of the 4 radiotracers ranged from 0.52 to 1.07. We then performed ELISA to measure their affinities to EGFR-TK; ELISA assay results indicated that each inhibitor was specifically bounded to EGFR-TK in a dose-dependent manner. The EGFR-TK autophosphorylation IC50 values of [18F]I, [18F]II, [18F]III, and [18F]IV were 7.732, 0.4698, 0.1174, and 0.1176?μM, respectively. All labeled compounds were evaluated via cellular uptake and blocking studies in HepG2 cell lines in vitro. Cellular uptake and blocking experiment results indicated that [18F]I and [18F]III had excellent cellular uptake at 120-minute postinjection in HepG2 carcinoma cells (51.80?±?3.42%ID/mg protein and 27.31?±?1.94%ID/mg protein, respectively). Additionally, biodistribution experiments in S180 tumor-bearing mice in vivo indicated that [18F]I had a very fast clearance in blood and a relatively high uptake ratio of tumor to blood (4.76) and tumor to muscle (1.82) at 60-minute postinjection. [18F]III had a quick clearance in plasma, and its highest uptake ratio of tumor to muscle was 2.55 at 15-minute postinjection. These experimental results and experiences were valuable for the further exploration of novel radiotracers of quinazoline derivatives.
Facile Synthesis of Novel Perfluorocarbon-Modulated 4-Anilinoquinazoline Analogues
Shi, Huiping,Lai, Bonan,Chen, Shizhen,Zhou, Xin,Nie, Jing,Ma, Jun-An
, p. 1693 - 1700 (2017/09/06)
4-Anilinoquinazoline analogues stand out among many kinds of small molecules that inhibit the tyrosine kinase activities of epidermal growth factor receptor (EGFR), thus serving as significant molecular targets for anticancer drug design. Herein, a series of novel perfluorocarbon (PFC) modulated 4-anilinoquinazolines were designed and prepared straightforwardly by nucleophilic substitution reaction of various anilinoquinazolines and PFC-derived methanesulfonate. In the presence of base, the reaction proceeded smoothly to afford a wide range of 4-anilinoquinazolines with different substituents on aniline moiety in good to high yields. Furthermore, the PFC-modified analogues of gefitinib and erlotinib were also obtained in 93% and 90% respectively, which may have potential for developing new inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase and fluorinated contrast agents (CA) for 19F MRI.
Model 18 F mark 4-amino-quinazoline derivatives and its preparation method and tumor PET imaging applications
-
, (2016/11/28)
The invention provides novel F marked 4-aminoquinazoline compounds. The novel F marked 4-aminoquinazoline compounds are characterized in that one end of each of the novel F marked 4-aminoquinazoline compounds has a 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.
Model 18 F mark substituted [...] compound and its preparation method and tumor PET imaging applications
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, (2017/01/09)
The invention provides a novel F marked substituted quinazoline compound. The novel F marked substituted quinazoline compound is characterized in that one end of the novel F marked substituted quinazoline compound has a F substituted alkyloxy structure; the other end of the compound has a 6,7-substituted quinazoline structure, and a substituent R1 is positioned in the 4 position of a quinazoline maternal, and is a 2-, 3-, 4-F substituted alkyloxy group; and a substituent R2 is positioned in the 6 position of the quinazoline maternal, and is a methoxyethoxy group, a methoxy group, or a morpholinepropanolato group. The structural formula of the compound is shown as A in the specification. Results of experiments show that the compound has the advantages of good bioactivity, good serum stability, low intake in tissues of the liver and the like, and high enrichment and slow removal rate in tumors, and the marking precursor of the compound has the advantages of easy synthesis, extremely high marking rate and the like, so the compound has a huge potential for the tumor PET development.
Design, synthesis and biological characterization of a new class of osteogenic (1H)-quinolone derivatives
Manetti, Fabrizio,Petricci, Elena,Gabrielli, Annalisa,Mann, Andrè,Faure, Hélène,Gorojankina, Tatiana,Brasseur, Laurent,Hoch, Lucile,Ruat, Martial,Taddei, Maurizio
supporting information, p. 747 - 757 (2016/07/21)
Smoothened (Smo) is the signal transducer of the Hedgehog (Hh) pathway and its stimulation is considered a potential powerful tool in regenerative medicine to treat severe tissue injuries. Starting from GSA-10, a recently reported Hh activator acting on Smo, we have designed and synthesized a new class of quinolone-based compounds. Modification and decoration of three different portions of the original scaffold led to compounds able to induce differentiation of multipotent mesenchymal cells into osteoblasts. The submicromolar activity of several of these new quinolones (0.4–0.9?μM) is comparable to or better than that of SAG and purmorphamine, two reference Smo agonists. Structure-activity relationships allow identification of several molecular determinants important for the activity of these compounds.
Novel [99mTcN]2+ labeled EGFR inhibitors as potential radiotracers for single photon emission computed tomography (SPECT) tumor imaging
Zhao, Mingxia,Ning, Hongyu,Feng, Man,Li, Shilei,Chang, Jin,Qi, Chuanmin
, p. 5508 - 5521 (2014/06/10)
The epidermal growth factor receptor (EGFR) is overexpressed in many cancers, including breast, ovarian, endometrial and non-small cell lung cancer. An EGFR-specific imaging agent could facilitate clinical evaluation of primary tumors or metastases. To achieve this goal, 4-(2-aminoethylamino)-6,7- dimethoxyquinazoline (ADMQ) was synthesized based on a 4-aminoquinazoline core and then conjugated with N-mercapto-acetylglycine (MAG) and N- mercaptoacetyltriglycine (MAG3), respectively, to give compounds 1 and 2. The final complexes [99mTcN]-1 and [99mTcN]-2 were successfully obtained with radiochemical purities of >99% and >98% as measured by radio-HPLC. No decomposition of the two complexes at room temperature was observed over a period of 2 h. Their partition coefficients indicated they were hydrophilic and the electrophoresis results showed they were negatively charged. Biodistribution in tumor-bearing mice demonstrated that the two new complexes showed tumor accumulation, high tumor-tomuscle (T/M) ratios and fast clearance from blood and muscle. Between the two compounds, the 99mTcN-MAG3-ADMQ ([99mTcN]-2) showed the better characteristics, with the tumor/muscle and tumor/blood ratios reached 2.11 and 1.90 at 60 min post-injection, 4.20 and 1.10 at 120 min post-injection, suggesting it could be a promising radiotracer for SPECT tumor imaging.
The first radiosynthesis of [11C]AZD8931 as a new potential PET agent for imaging of EGFR, HER2 and HER3 signaling
Wang, Min,Gao, Mingzhang,Zheng, Qi-Huang
, p. 4455 - 4459 (2014/12/11)
The reference standard AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-methylacetamide} (11a) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-chloro-N-methylacetamide in 11 steps with 2-5% overall chemical yield. The precursor N-desmethyl-AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)acetamide} (11b) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-bromoacetamide in 11 steps with 2-4% overall chemical yield. The target tracer [11C]AZD8931 {2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-[11C]methylacetamide} ([11C]11a) was prepared from N-desmethyl-AZD8931 (11b) with [11C]CH3OTf under basic condition (NaH) through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [11C]CO2and decay corrected to end of bombardment (EOB) with 370-1110 GBq/μmol specific activity at EOB.
Design and synthesis of novel quinazoline nitrogen mustard derivatives as potential therapeutic agents for cancer
Li, Shilei,Wang, Xiao,He, Yong,Zhao, Mingxia,Chen, Yurong,Xu, Jingli,Feng, Man,Chang, Jin,Ning, Hongyu,Qi, Chuanmin
, p. 293 - 301 (2013/10/01)
Thirteen novel quinazoline nitrogen mustard derivatives were designed, synthesized and evaluated for their anticancer activities in vitro and in vivo. Cytotoxicity assays were carried out in five cancer cell lines (HepG2, SH-SY5Y, DU145, MCF-7 and A549) and one normal human cell line (GES-1), in which compound 22b showed very low IC50 to HepG2 (the IC50 value is 3.06 μM), which was lower than Sorafenib. Compound 22b could inhibit cell cycle at S and G2/M phase and induce cell apoptosis. In the HepG2 xenograft model, 22b exhibited significant cancer growth inhibition with low host toxicity in vivo.
Synthesis and evaluation of novel F-18 labeled 4-aminoquinazoline derivatives: Potential PET imaging agents for tumor detection
Chen, Yurong,Feng, Man,Li, Shilei,Xu, Jingli,Ning, Hongyu,He, Yong,Wang, Xiao,Ding, Rui,Qi, Chuanmin
, p. 4745 - 4749 (2012/08/07)
Three novel 18F-labeled 4-aminoquinazoline derivatives, N-(3-chloro-4-fluorophenyl)-6-(2-[18F]fluoroethoxy)-7- methoxyquinazolin-4-amine([18F]1), N-(3-ethynylphenyl)-6-(2-[ 18F]fluoroethoxy)-7-methoxyquinazolin-4-amine([18F]2), and N-(3-bromophenyl)-6-(2-[18F]fluoroethoxy)-7-methoxyquinazolin-4- amine([18F]3) were synthesized and radiolabeled by two-step reaction with overall radiochemical yield of 21-24% (without decay corrected). Then we carried out their biodistribution experiments in S180 tumor-bearing mice. Results showed that they had certain concentration accumulation in tumor and fast clearance from muscle and blood. It was encouraging that [18F]3 was competitive among three 18F-labeled 4-aminoquinazoline derivatives in some aspects such as tumor/muscle uptake ratio reaching 7.70 at 60 min post-injection, tumor/blood uptake ratio reaching 6.61 at 120 min post-injection. So we compared radioactivity characteristics of [ 18F]3 with those of [18F]-FDG and L-[18F]-FET in the same animal model. The absolute radioactivity uptake of [18F]3 in tumor reached 3.31 at 60 min p.i., which was slightly higher than [ 18F]-FDG (2.16) and L-[18F]-FET (2.75) at the same time phase. For [18F]3, tumor/muscle uptake ratio peaked 7.70 at 60 min, which was obviously superior to those of [18F]-FDG and L-[ 18F]-FET at all time points. The tumor/brain uptake ratios of [ 18F]3 were 10.36, 17.42, 41.11 at 30 min, 60 min and 120 min post-injection, respectively, and are much higher than those of L-[ 18F] FET (2.54, 2.92 and 2.95) and [18F]-FDG (0.61, 1.02 and 1.33) at the same time points. All these results indicate that [ 18F]3 is promising to become a potential PET tumor imaging agent.
