- Novel mTOR inhibitor compounds and the use thereof
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The novel mTOR inhibitor compounds of the present invention are capable of selective drug delivery to bone and released slowly in bone for a long period of time. The present invention relates to a targeted compound linked to a mTOR inhibitory bone disease therapeutic agent.
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Paragraph 0085-0088; 0094-0096
(2021/03/09)
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- Novel mTOR inhibitor compounds and the use thereof
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The novel mTOR inhibitor compounds of the present invention are capable of selective drug delivery to bone and released slowly in bone for a long period of time. The present invention relates to a targeted compound linked to a mTOR inhibitory bone disease therapeutic agent.
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Paragraph 0113-0118; 0122-0124
(2021/03/16)
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- Novel [99mTcN]2+ labeled EGFR inhibitors as potential radiotracers for single photon emission computed tomography (SPECT) tumor imaging
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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.
- Zhao, Mingxia,Ning, Hongyu,Feng, Man,Li, Shilei,Chang, Jin,Qi, Chuanmin
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p. 5508 - 5521
(2014/06/10)
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- Preparation and bioevaluation of 99mTc nitrido radiopharmaceuticals with pyrazolo[1,5-a]pyrimidine as tumor imaging agents
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The 7-(2-aminoethylamino)-5-methyl-3-cyanopyrazolo[ 1,5-a]pyrimidine (AMCPP) was synthesized and conjugated with N-mercaptoacetylglycine (MAG), N-mercaptoacetylphenylalanine (MAF), and N-mercaptoacetylvaline (MAA), respectively. These three compounds were labeled successfully with [ 99mTcN]2+ intermediate in high radiochemical purities. Biodistribution in tumor-bearing mice demonstrated that the three new complexes showed high tumor-to-muscle (T/M) ratios and rapid clearance from the blood, muscle, liver, kidney, and lung. Among them, the 99mTcN-MAG-AMCPP showed the most favorable characteristics. The tumor/blood and tumor/muscle ratios reached 1.50 and 1.15 at 30 min post-injection, 2.20 and 1.83 at 60 min post-injection. Springer Science+Business Media, LLC 2011.
- Ding, Rui,He, Yong,Xu, Jingli,Liu, Hang,Wang, Xiao,Feng, Man,Qi, Chuanmin,Zhang, Junbo,Peng, Cheng
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experimental part
p. 523 - 530
(2012/09/07)
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- Synthesis and biological evaluation of pyrazolo[1,5-a]-pyrimidine- containing 99mTc nitrido radiopharmaceuticals as imaging agents for tumors
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The compound 5-((2-aminoethylamino)methyl)-7-(4-bromoanilino)-3- cyanopyrazolo[ 1,5-a]pyrimidine (ABCPP) was synthesized and conjugated with N-mercaptoacetylglycine (MAG), N-mercaptoacetylphenylalanine (MAF) and N-mercaptoacetylvaline (MAA), respectively. These three compounds were labeled successfully with [99mTcN]2+ intermediate in high radiochemical purities. Biodistribution in tumor-bearing mice demonstrated that the three new complexes showed tumor accumulation, high tumor-tomuscle (T/M) ratios and fast clearance from blood and muscle. Among them, the 99mTcNMAG-ABCPP showed the most favorable characteristics, with tumor/blood and tumor/muscle ratios reaching 1.51 and 2.97 at 30 min post-injection, 1.84 and 2.49 at 60 min post-injection, suggesting it could be further studied as potential tumor imaging agent for single photon emission computed tomography (SPECT).
- Ding, Rui,He, Yong,Xu, Jingli,Liu, Hang,Wang, Xiao,Feng, Man,Qi, Chuanmin,Zhang, Junbo
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scheme or table
p. 8723 - 8733
(2011/02/28)
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- Synthesis and biological evaluation of technetium-99m-labeled deoxyglucose derivatives as imaging agents for tumor
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Three deoxyglucose (DG) derivatives, S-DG, MAG3-DG and MAMA-BA-DG, were synthesized and labeled successfully with high labeling yields and high radio-chemical purities. Biodistribution in tumor-bearing mice demonstrated that these three new su
- Chen, Xiangji,Li, Liang,Liu, Fei,Liu, Boli
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p. 5503 - 5506
(2007/10/03)
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- Synthesis, biodistribution and qsar studies of five Tc-99M labeled novel N3S pseudo-peptide complexes
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Five novel N3S pseudo-peptide chelators derived from mercaptoacetic acid have been synthesized and characterized based on the spectroscopic data. All the chelators were labeled with Technicium-99m to evaluate their biological activities. Invest
- Zhang, Hua-Bei,Ye, Hai-Hong,Zhang, Ya-Ling,Zheng, Xuefang,Han, Jian-Sheng,Li, Hua,Liu, Chun-Ping
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- Design and synthesis of a novel family of semi-rigid ligands: Versatile compounds for the preparation of 99mTc radiopharmaceuticals
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Synthetic pathways to a range of novel semi-rigid tetradentate ligands, with sulfur, amido or amino donor groups, designed to coordinate technetium 99m have been developed. The technetium-99m complexes have been prepared and their stabilities in serum and
- Le Gal, Julien,Latapie, Laure,Gressier, Marie,Coulais, Yvon,Dartiguenave, Michele,Benoist, Eric
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p. 876 - 883
(2007/10/03)
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- Synthesis and characterization of novel N3S chelators and biodistribution of their 99Tcm labeled complexes as potential kidney imaging agents
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Two new target chelators were synthesized through five steps with mercaptoacetic acid as the primary material, and identified by spectroscopy data including IR, 1HNMR, 13CNMR, Ms as new kidney imaging agents. The chelators were label
- Qi, Chuan-Min,Feng, Shu-Juan,Zhang, Hua-Bei,Huang, Hai-Bo,Li, Bo
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p. 471 - 480
(2007/10/03)
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- A practical approach to the synthesis of hairpin polyamide-peptide conjugates through the use of a safety-catch linker
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Hairpin polyamides are high-affinity, sequence selective DNA binders. The use of a safety-catch linker for the solid phase synthesis of hairpin polyamides allows for easy preparation of derivatives ready for chemoselective ligation with unprotected peptides. Examples of ligations reported include thioether bond formation and thioester-mediated amide bond formation ('Native Chemical Ligation').
- Fattori, Daniela,Kinzel, Olaf,Ingallinella, Paolo,Bianchi, Elisabetta,Pessi, Antonello
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p. 1143 - 1147
(2007/10/03)
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- Synthesis of novel N3S pseudo-peptide and biodistribution of 99Tcm-pseudo-peptide complexes in mice
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An excellent reaction condition of active ester with amine acid was developed, and a series of novel N3S pseudo-peptide chelators starting from mercaptoacetic acid were synthesized and characterized based on the spectroscopic data, such as IR,
- Qi, Chuan-Min,Yang, Ling-Chun,Zhang, Hua-Bei,Guo, Xue-Feng,Feng, Shu-Juan,Li, Bo
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p. 345 - 359
(2007/10/03)
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- Synthesis, high-field NMR, X-ray structure, and conformational analysis of a 10-membered diamide disulfide ring
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N,N′-[Dimethyl-(2,2′-dithiobisacetyl)]ethylenediamine (1) has been synthesized in 30% overall yield from N,N′-dimethylethylenediamine and thioacetic acid by an improved procedure involving simultaneous deprotection and oxidative cyclization with iodine. T
- Maharajh, Rabindranath B.,Snyder, James P.,Britten, James F.,Bell, Russell A.
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p. 140 - 161
(2007/10/03)
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- Comparison of the labelling characteristics of mercaptoacetyltriglycine (MAG3) with different S-protective groups
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A number of different thiol protective groups have been synthesized and attached to mercaptoacetyltriglycine (MAG3) ligand. The newly made MAG3 analogues were labelled with 99mTc by direct labelling under alkaline condition and by stannous tartrate exchange labelling method. In the latter method, the amount of the ligand, reaction temperature and pH varied and their effects on the labelling efficiencies were studied. Radiochemical purities of 51% to 70%, 58% to 75% and 46% to 81% respectively, were obtained by radio-HPLC analysis for the studied MAG3 precursors when, 0.1 mg, 0.4 mg and 1.6 mg of the ligand was used and labelling was performed at both low temperature (70°C) and pH (pH 3). All the studied ligands were efficiently labelled with 99mTc (up to 99%) when heated for 10 min at pH 9 and 100°C. The labelling efficiency obtained by the direct labelling method for MAG3 analogues varied from 32% to 94% and was in all cases lower than after the exchange labelling at pH 9 and at 100°C. It was observed that the radiochemical purities can be improved significantly by heating the 'direct labelling mixture' at elevated temperature.
- Okarvi, Subhani M.,Adriaens, Paul,Verbruggen
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p. 853 - 874
(2007/10/03)
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- The synthesis and high-resolution NMR spectroscopy of ethyl N-(2-triphenylmethylthio)ethanoyl-O-{4′-[4″-(1″-bis(2?- chloroethyl)amino)phenyl]butanoyl}-L-seryl-S-benzyl-L-cysteine: A chelate-chlorambucil complex for use as a ligand for 99mTc rad
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A potential agent for the imaging of tumours has been synthesized from the antineoplastic agent chlorambucil. Standard peptide coupling techniques were used to synthesize a tripeptide covalently coupled to chlorambucil in 10 steps. The final product was c
- Bell, Russell A.,Hughes, Donald W.,Lock, Colin J.L.,Valliant, John F.
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p. 1502 - 1511
(2007/10/03)
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- Synthesis and characterization of cyclomaltoheptaose-based metal chelants as probes for intestinal permeability
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The syntheses of two cyclomaltoheptaose-based metal chelants, cyclomaltoheptaose-ethylenediaminetetraacetate (CD-EDTA) and cyclomaltoheptaose-diamide-disulfur (CD-DADS), are described. The chelant moieties are attached to the 6-position of a single pyranose in the cyclomaltoheptaose via a short diamine spacer chain. Characterization of these novel chelants has been achieved using NMR and MS techniques. The peculiar fluxional properties of the CD-EDTA molecules is also discussed.
- Capretta,Maharajh,Bell
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