- Synthesis and physicochemical properties of merocyanine dyes based on dihydropyridine and fragments of cyanoacetic acid derivatives
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Merocyanine dyes of the dihydropyridine series were prepared from salts of α(γ)-picolinium and cyanoacetic acid derivatives. Their spectral characteristics suggesting their structure in solution were studied. The change in the spectral properties depending on the substituents introduced into the structure of the substituents and solvents used (solvatochromism) was considered. The protonation of the dyes was studied, and its regioselectivity was established.
- Borisova, Irina A.,Zubarev, Andrey A.,Rodinovskaya, Lyudmila A.,Shestopalov, Anatoliy M.
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- 18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: Synthesis from 2,4-dinitrobenzamide and tosylate precursors and comparative biological evaluation for tumor imaging with positron emission tomography
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We previously reported 18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: 7-(2-[18F]fluoroethylamino)-5-methylpyrazolo[1,5-a] pyrimidine-3-carbonitrile ([18F]1) and N-(2-(3-cyano-5- methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[18F]fluoro-4- nitrobenzamide ([18F]2). Preliminary biodistribution experiments of both compounds showed s slow clearance rate from excretory tissues which warranted further investigation for tumor imaging with PET. Here we modified [18F]1 and [18F]2 by introducing polar groups such as ester, hydroxyl and carboxyl and developed three additional 18F-18 labeled pyrazolo[1,5-a] pyrimidine derivatives: (3-Cyano-7-(2-[ 18F]fluoroethylamino)pyrazolo[1,5-a]-pyrimidin-5- yl)methyl acetate ([18F]3), 7-(2-[18F]fluoroethylamino)-5-(hydroxymethyl) pyrazolo[1,5-a]- pyrimidine-3-carbonitrile ([18F]4) and (S)-6-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7- ylamino)-2-(2-[ 18F]fluoro-4-nitrobenzamido)hexanoic acid ([18F]5). The radiolabeled probes were synthesized by nucleophilic substitution of the corresponding tosylate and nitro precursors with 18F-fluoride. In Vitro studies showed higher uptake of [18F]3 and [18F]4 than that of [18F]5 by S180 tumor cells. In Vivo biodistribution studies in mice bearing S180 tumors showed that the uptake of both [ 18F]3 and [18F]4 in tumors displayed an increasing trend while the uptake of [18F]5 in tumor decreased through the course of the 120 min study. This significant difference in tumor uptake was also found between [18F]1 and [18F]2. Thus, we compared the biological behavior of the five tracers and reported the tumor uptake kinetic differences between 2-[18F]fluoroethylamino- and 2-[ 18F]fluoro-4-nitro- benzamidopyrazolo[1,5-a] pyrimidine derivatives.
- Xu, Jingli,Liu, Hang,Li, Guixia,He, Yong,Ding, Rui,Wang, Xiao,Feng, Man,Zhang, Shuting,Chen, Yurong,Li, Shilei,Zhao, Mingxia,Li, Yingruo,Qi, Chuanmin,Dang, Yonghong
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- Spectroscopic Investigations of Merocyanines-1. UV- and NMR-Spectra of Malodintrile-Substituted Vinylogen Acid Amides.
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UV and NMR spectra of open chained merocyanine dyes are investigated and model calculations are performed within the Pariser Parr Pople approximation. The introduction of charged pseudo centers permits the calculation of the solvent dependent shifts in the electronic absorption spectra. A good correlation is also found between computed pi -charge densities and observed **1H chemical shifts. Due to the high electronegativity of the malonitrile group, the electronic structure and spectroscopic behavior of the investigated compounds approach that of the symmetrical polymethine dyes.
- Scheibe,Schneider,Doerr,Daltrozzo
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p. 630 - 638,631,632,634,636
(1976)
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Read Online
- NMR spectroscopic data of some 1-alkoxy-2,2-di(carbonyl, carboxyl, cyano)-substituted ethylenes
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The 1H-13C NMR shifts as well as 1H and 13C coupling constants of 14 alkoxymethylene malonic acid and acetoacetic acid derivatives and two alkoxymethylene acetylacetones are reported. The 17O NMR spectra have been recorded for six of them. The long-range coupling 3J(H-C=C-CR) has been used for determining the stereochemistry of the double bond. Copyright
- Hametner, Christian,Cernuchova, Petra,Milata, Viktor,Vo-Thanh, Giang,Loupy, Andre
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- Synthesis and biological evaluation of some acyclic 4,6-disubstituted 1H-pyrazolo[3,4-d]pyrimidine nucleosides
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The chemical synthesis and biological evaluation of some acyclic α-[6-(1′-carbamoylalkylthio)-1H-pyrazolo[3,4-d]pyrimidin-4-yl] thioalkylamide nucleosides are described.
- Moukha-Chafiq,Taha,Mouma,Lazrek,Vasseur,De Clercq
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Read Online
- GLUCOSE UPTAKE INHIBITORS AND USES THEREOF
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The present invention relates to novel compounds that modulate cellular glucose uptake by affecting various targets, including, but not limited to those related to glycolysis and known transporters/co-transporters of the GLUT family. The compounds according to the invention are useful for treating cancer such as: neuroendrocrine neoplasms, gastrointestinal stromal tumors (GIST), renal cell carcinoma, paraganglioma, pheochromocytoma, pituitary adenoma, colorectal cancer, lung cancer, gastric cancer, pancreatic cancer sarcoma, head and neck cancer, melanoma, ovarian cancer and other cancers that rely on high levels of glycolysis for survival and proliferation; as well as in treating of autoimmune diseases, inflammation, infectious diseases, and metabolic diseases.
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Paragraph 00272; 00420
(2021/05/21)
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- Triflic acid-mediated N-heteroannulation of β-anilino-β-(methylthio)acrylonitriles: a facile synthesis of 4-amino-2-(methylthio)quinolines
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Various functionalised 4-amino-2-(methylthio)quinolines are synthesised through triflic acid-mediated N-heteroannulation of α-functionalized-β-anilino-β-(methylthio)acrylonitriles for the first time. The N-heteroannulation process is highly chemoselective and has mild reaction conditions. However, this process fails in the absence of the β-methylthio group in the acrylonitriles. In addition, a new double N-heteroannulation process is demonstrated to synthesise indolo[3,2-c]quinolines from non-heterocyclic precursors. Natural product isocryptolepine is synthesised in four steps from an acyclic precursor.
- Bandyopadhyay, Debashruti,Panigrahi, Adyasha,Peruncheralathan, S.,Radhakrishnan, Divya,Thirupathi, Annaram
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supporting information
p. 8544 - 8553
(2021/10/20)
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- Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies
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Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential. These fragments include hydrazone, indoline-2-one, phthalimide, thiourea, oxadiazole, pyrazole, and dihydropyrazole. The synthesized molecules were evaluated for their anticancer activity against the human breast cancer cell line, MCF-7. The obtained results revealed comparable antitumor activity with that of the reference drugs doxorubicin and toceranib. Docking studies were performed along with EGFR-TK and ADMET profiling studies. The results of the docking studies showed the ability of the designed compounds to interact with key residues of the EGFR-TK through a number of covalent and noncovalent interactions. The obtained activity of compound 25 (IC50 = 2.89 μM) suggested that it may serve as a lead for further optimization and drug development.
- Abulkhair, Hamada S.,Al-Karmalawy, Ahmed A.,Bayoumi, Ashraf H.,El-Adl, Khaled,El-Gamal, Kamal M.,El-Morsy, Ahmed M.,Ezz Eldin, Rogy R.,Gaber, Ahmed A.,Saleh, Marwa A.,Sherbiny, Farag F.
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- Continuous synthesis method of ethoxymethylene malononitrile (by machine translation)
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The method comprises the following steps, continuously discharging the malononitrile: raw formic acid ester and acetic anhydride into the continuous reaction equipment for replacing the reaction, to obtain the ethoxymethylene malononitrile, and continuously heating the raw materials to the reaction temperature, in a substitution reaction process . and ; The method comprises the following steps of continuously discharging, DEG, malononitrile 1:(0.9-6.0):(2.0-6.0) .raw formic acid ester and acetic anhydride through a continuous reactor, in a continuous reaction device, in a continuous reaction device in a substitution reaction process to obtain the ethyoxyl methylene malononitrile in the continuous reaction equipment at, DEG C in the process of the process of the present invention; and the method comprises the step of continuously, synthesizing the raw materials . The method comprises the following steps of: reducing, safety risks. (by machine translation)
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Paragraph 0034-0075
(2020/05/08)
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- Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy
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PDE5 targeting represents a new and promising strategy for apoptosis induction and inhibition of tumor cell growth due to its over-expression in diverse types of human carcinomas. Accordingly, we report the synthesis of series of pyrazolo[3,4-d]pyrimidin-4-one carrying quinoline moiety (11a-r) with potential dual PDE5 inhibition and apoptotic induction for cancer treatment. These hybrids were structurally elucidated and characterized with variant spectroscopic techniques as 1H NMR, 13C NMR and elemental analysis. The assessment of their anticancer activities has been declared. All the rationalized compounds 11a-r have been selected for their cytotoxic activity screening by NCI against 60 cell lines. Compounds 11a, 11b, 11j and 11k were the most active hybrids. Among all, compound 11j was further selected for five dose tesing and it displayed outstanding activity with strong antitumor activity against the nine tumor subpanels tested with selectivity ratios ranging from 0.019 to 8.3 at the GI50 level. Further, the most active targets 11a, b, j and k were screened for their PDE5 inhibitory activity, compound 11j (with IC50 1.57 nM) exhibited the most potent PDE5 inhibitory activity. Moreover, compound 11j is also showed moderate EGFR inhibition with IC50 of 5.827 ± 0.46 μM, but significantly inhibited the Wnt/β-catenin pathway with IC501286.96 ± 12.37 ng/mL. In addition, compound 11j induced the intrinsic apoptotic mitochondrial pathway in HepG2 cells as evidenced by the lower expression levels of the anti-apoptotic Bcl-2 protein, and the higher expression of the pro-apoptotic protein Bax, p53, cytochrome c and the up-regulated active caspase-9 and caspase-3 levels. All results confirmed by western blotting assay. Compound 11j exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase. In conclusion, hybridization of quinoline moiety with the privileged pyrazolo[3,4-d]pyrimidinon-4-one structure resulted in highly potent anticancer agent, 11j, which deserves more study, in particular, in vivo and clinical investiagtions, and it is expected that these results would be applied for more drug discovery process.
- Ibrahim, Tarek S.,Hawwas, Mohamed M.,Taher, Ehab S.,Alhakamy, Nabil A.,Alfaleh, Mohamed A.,Elagawany, Mohamed,Elgendy, Bahaa,Zayed, Gamal M.,Mohamed, Mamdouh F.A.,Abdel-Samii, Zakaria K.,Elshaier, Yaseen A.M.M.
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- Ultrasonic-Assisted Synthesis of Pyrazolo[3,4-d]pyrimidin-4-ol Tethered with 1,2,3-Triazoles and Their Anticancer Activity
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Abstract: In the presents work synthesis and characterization of new heterocyclic derivatives containing pyrazolo[3,4-d]pyrimidine linkage with 1,4-disubstituted-1,2,3-triazoles via methylene-oxy group. The selected synthesized compounds were tested for their in-vitro anticancer activity against various cancer cell lines. Synthesis of compounds was done under ultrasonic-assisted Huisgen 1,3-dipolar cycloaddition reaction with good yields. Some of the newly synthesized compounds demonstrated good to moderate anticancer activity, most of compounds shows activity against renal cancer cell lines.
- Bhatt, Tejal D.,Gojiya, Dinesh G.,Hadiyal, Sanjay D.,Joshi, Dr. Hitendra S.,Kapupara, Vimal H.,Prakash, L. Kalavadiya
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p. 803 - 813
(2020/10/29)
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- Pyrazolo [1, 5 - a] pyrimidine nitrogen mustard derivative and its preparation method and tumor therapeutic use
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The invention relates to pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives or medical salts thereof, as well as application of the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives or the medical salts thereof. The pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives and the medical salts thereof have the structure shown as the formula I. Pharmacological experiments show that the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives and the medical salts thereof have inhibiting effects on the proliferation of various tumor cells. Moreover, the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives are small in toxicity, have the advantages of selectivity on tumor cells, and are dual-functional anti-tumor drugs. Meanwhile, the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives are easy to synthesize, and the overall yields are high. All the advantages show that the pyrazolo[1,5-alpha] pyrimidine nitrogen mustard derivatives have great potential of being anti-tumor drugs.
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Paragraph 0086; 0087; 0088; 0089; 0090
(2017/08/02)
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- Discovery of a potent protein kinase D inhibitor: insights in the binding mode of pyrazolo[3,4-d]pyrimidine analogues
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In this study, we set out to rationally optimize PKD inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold. The lead compound for this study was 1-NM-PP1, which was previously found by us and others to inhibit PKD. In our screening we identified one compound (3-IN-PP1) displaying a 10-fold increase in potency over 1-NM-PP1, opening new possibilities for specific protein kinase inhibitors for kinases that show sensitivity towards pyrazolo[3,4-d]pyrimidine derived compounds. Interestingly the observed SAR was not in complete agreement with the commonly observed binding mode where the pyrazolo[3,4-d]pyrimidine compounds are bound in a similar fashion as PKD's natural ligand ATP. Therefore we suggest an alternate binding mode where the compounds are flipped 180 degrees. This possible alternate binding mode for pyrazolo[3,4-d]pyrimidine based compounds could pave the way for a new class of specific protein kinase inhibitors for kinases sensitive towards pyrazolo[3,4-d]pyrmidines.
- Verschueren, Klaas,Cobbaut, Mathias,Demaerel, Joachim,Saadah, Lina,Voet, Arnout R. D.,Van Lint, Johan,De Borggraeve, Wim M.
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supporting information
p. 640 - 646
(2017/03/30)
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- Synthesis, anti-inflammatory and molecular docking study of schiff bases containing methanesulphonyl pharmacophore
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Background: A series of 5-(arylideneamino)-1H-pyrazole-4-carbonitriles 8a-h was synthesized via reaction of triethylorthoformate 1 with malononitrile 2 in presence of acetic anhydride to give ethoxymethylenemalononitrile 3. Compound 3 was reacted with 4-methanesulfonylphenylhydrazine 4 to give 5-amino-1H-pyrazole-4-carbonitrile 5 that condensed with different aromatic aldehydes 6a-h in presence of the ionic liquid morpholinium hydrogen sulphate 7 to form the target 5-(arylideneamino)-1H-pyrazole-4-carbonitrile compounds 8a-h. Methods: All the synthesized compounds were evaluated for their cyclooxygenase selectivity, antiinflammatory, and molecular docking study for COX2 enzyme. 8a and 8e were the most potent COX-2 inhibitors (IC50 = 0.98, 1.3 μM respectively). Results: While most compounds showed good anti-inflammatory activity at all time intervals (1, 3 and 5 h), 8d derivative displayed the highest anti-inflammatory activities (94.61, 98.35, and 99.92%, respectively) and the most COX-2 selective derivatives 8a and 8e showed considerable potency (47.43, 88.94, and 98.44% respectively for 8a and 51.90, 89.13, and 98.20% respectively for 8e) comparable to that of celecoxib (92.77, 97.77, and 99.51% respectively). Also, 8d showed less ulceration effect (ulcer index = 2.9) than celecoxib (ulcer index = 3.35) and aspirin (ulcer index 22.75). Conclusion: Additionally, all the tested compounds showed good binding affinity for COX2 enzyme in the molecular docking studies.
- Abdellatif, Khaled R.A.,Elsaady, Mohammed T.,Abdel-Aziz, Salah A.,AbuSabah, Ahmed H.A.
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p. 930 - 937
(2017/08/29)
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- Synthesis, in vitro and in vivo anticancer activity of novel 1-(4-imino-1-substituted-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl)urea derivatives
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A series of pyrazolo[3,4-d]pyrimidine and urea hybrids have been designed, synthesized and evaluated for their anticancer activity in vitro and in vivo cancer models. Among them, compounds 28, 30, 33, 36 and 37 showed promising cytotoxicity against tested cancer cell lines. Compound 37 (CBS-1) appeared as the most active derivative and it exhibited better cytotoxicity against all tested cell lines as compared to doxorubicin. CBS-1 successfully inhibited cell cycle progression and displayed good apoptosis in A549 cells. CBS-1 significantly induced caspase-3 activation and suppressed NF-κB and IL-6 activation in immunocytochemistry, qPCR and western blot analysis. Additionally, CBS-1 prominently displayed tumoricidal effects in lung adenocarcinoma in vivo xenograft nude mice model.
- Mishra, Chandra Bhushan,Mongre, Raj Kumar,Kumari, Shikha,Jeong, Dong Kee,Tiwari, Manisha
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p. 24491 - 24500
(2016/03/15)
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- Quinazoline derivative and preparation method and application thereof
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The invention relates to a quinazoline derivative and a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The structure of the quinazoline derivative is as shown in a formula I. The quinazoline derivative or a pharmaceutically acceptable salt thereof has an irreversible inhibition effect on tyrosine kinase, the compound can inhibit two kinds of tyrosine kinase of EGFR and HER2 simultaneously, and the compound has good inhibitory activity on multiple cancer cell lines. Please see the formula I in the description.
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Paragraph 0214; 0217; 0218; 0219
(2016/12/26)
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- PROCESS OF PREPARATION OF AZIMSULFURON
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The present disclosure provides process for preparation of azimsulfuron or its salts, isomers, and other derivatives thereof. The process involves treating a compound of formula I, with aqueous acetic acid or formic acid and chlorine gas or sodium hypochlorite in presence of hydrochloric acid in chlorinated solvents such as dichloromethane, 1,2-dichloroethane or with aqueous acetic acid and N-chlorosuccinimide or hydrogen peroxide in presence of hydrochloric acid in aqueous cyclic ether such as tetrahydrofuran, 1,4-dioxane to obtain 1-methyl-4-(2-methyl-2H-tetrazol-5-yl)-1H-pyrazole-5-sulfonyl chloride; converting the sulfonyl chloride to a sulfonamide and treating the sulfonamide with a phenyl(4,6-dimethoxypyrimidin-2-yl) carbamate to obtain azimsulfuron or its salts, isomers, and other derivatives thereof.
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Paragraph 0209
(2015/04/28)
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- SUBSTITUTED TETRAZOLE COMPOUNDS AND PROCESS THEREOF
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The present disclosure provides a compound of formula I, its derivatives, salts, stereo-isomers, or regio-isomers thereof, useful as intermediates in preparation of sulfonamide or sulfonyl urea growth regulators or herbicides. Formula I The present disclosure further provides a process for preparing compound of formula I, its derivatives, salts, stereo-isomers, or regio-isomers thereof.
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Page/Page column 96
(2014/01/17)
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- SUBSTITUTUED PYRAZOLE COMPOUNDS AND PROCESS FOR PREPARATION THEREOF.
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The present disclosure provides a compound of formula I, its derivatives, salts, stereo-isomers, or regio-isomers thereof, useful as intermediates in preparation of sulfonamide or sulfonyl urea growth regulators or herbicides. Formula I The present disclosure further provides a process for preparing compound of formula I, its derivatives, salts, stereo-isomers, or regio-isomers thereof.
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Page/Page column 79
(2014/01/17)
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- PROCESS OF PREPARATION OF AZIMSULFURON
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The present disclosure provides process for preparation of azimsulfuron or its salts, isomers, and other derivatives thereof. The process involves treating a compound of formula I, (Formula I should be inserted here.) with aqueous acetic acid or formic acid and chlorine gas or sodium hypochlorite in presence of hydrochloric acid in chlorinated solvents such as dichloromethane, 1,2-dichloroethane or with aqueous acetic acid and N-chlorosuccinimide or hydrogen peroxide in presence of hydrochloric acid in aqueous cyclic ether such as tetrahydrofuran, 1,4-dioxane to obtain 1-methyl-4-(2-methyl-2H-tetrazol-5-yl)-1H-pyrazole-5-sulfonyl chloride; converting the sulfonyl chloride to a sulfonamide and treating the sulfonamide with a phenyl(4,6-dimethoxypyrimidin-2-yl) carbamate to obtain azimsulfuron or its salts, isomers, and other derivatives thereof.
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Page/Page column 37; 38
(2014/01/17)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Paragraph 0174 - 0175
(2014/05/24)
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- Synthetic methods for preparing ionic liquids containing hypophosphite and carbon-extended dicyanamide anions
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Chemical methodology: New synthetic methods to prepare ionic liquids containing the hypophosphite (HP) and carbon-extended dicyanamide (DCA) anions (vinylogous DCA and N,N′-dicyanoformamide (DCF)) have been developed (see scheme). The performance of these materials as hypergolic ionic liquids has also been evaluated. Copyright
- MacIejewski, John P.,Gao, Haixiang,Shreeve, Jean'Ne M.
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p. 2947 - 2950
(2013/03/28)
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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 novel F-18 labeled pyrazolo[1,5-a]pyrimidine derivatives: Potential PET imaging agents for tumor detection
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Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[18F] fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([ 18F]FEMPPC, [18F]1) and N-(2-(3-cyano-5-methylpyrazolo[1, 5-a]pyrimidin-7-ylamino)ethyl)-2-[18F]fluoro-4-nitrobenzamide ([ 18F]FCMPPN, [18F]2), have been designed and successively labeled with 18F by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60 min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [18F]1 and [18F]2 with those of [18F]FDG and L-[18F]FET in S180 tumor cells. Furthermore, the tumor uptake of [18F]1 and [ 18F]2 was assessed in mice bearing S180 tumor and compared with [18F]FDG and L-[18F]FET in the same animal model. In vitro cell uptake studies showed [18F]1 had higher uptake than [ 18F]FDG, [18F]2 and L-[18F]FET over the 2 h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [ 18F]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[18F]FET (2.43, 2.54, 2.93 and 2.95) and [18F]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What's more, the uptake of [18F]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[18F]FET before 30 min and [18F]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [18F]1 were superior to those of [18F]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [ 18F]1 at 30 min were higher than those of L-[18F]FET at the same time point. MicroPET image of [18F]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [ 18F]1 could be a new probe for PET tumor imaging.
- Xu, Jingli,Liu, Hang,Li, Guixia,He, Yong,Ding, Rui,Wang, Xiao,Feng, Man,Zhang, Shuting,Chen, Yurong,Li, Shilei,Zhao, Mingxia,Qi, Chuanmin,Dang, Yonghong
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scheme or table
p. 4736 - 4741
(2011/09/20)
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- THERAPEUTIC COMPOSITIONS AND RELATED METHODS OF USE
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Compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
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Page/Page column 113
(2010/11/03)
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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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- PROCESS FOR PRODUCING 5-AMINOPYRAZOLE DERIVATIVE, AND AZO DYE
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A process for producing a 5-aminopyrazole derivative represented by Formula (I) includes a step of reacting a hydrazine compound represented by Formula (II) with a compound represented by Formula (III) under a condition satisfying Reaction Condition 1 and Reaction Condition 2, wherein Reaction Condition 1 is that the reaction is conducted in a reaction solvent containing water, and Reaction Condition 2 is that pH of a liquid mixture containing the hydrazine compound represented by Formula (II), the compound represented by Formula (III), the reaction solvent, and an acidifying agent upon charging is within a range of from 2.0 to 4.0 at 25°c wherein the symbols in the formulae (I) to (III) are defined in the specification.
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Page/Page column 57; 58
(2008/12/05)
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- Microwave-assisted synthesis of substituted pyrazoles and pyrazolo [3,4-d]thiopyrimidines
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Ethyl(ethoxymethylene)cyanoacetate and ethoxymethylene malononitrile were synthesized from the reaction of malononitrile or ethylcyanoacetate with triethyl orthoformate or orthoacetate in N, N-dimethylacetamide under microwave irradiation. In a similar manner, substituted pyrazoles were synthesized from the reaction of ethyl (ethoxymethylene)cyanoacetate and ethoxymethylene malononitrile with phenylhydrazine. These pyrazoles were converted to pyrazolo[3,4-d]thiopyrimidines upon treatment with arylisothiocyanate and thiourea under microwave irradiation. Copyright Taylor & Francis Group, LLC.
- Heravi, Majid M.,Nami, Navabeh,Seifi, Nasim,Oskooie, Hossein A.,Hekmatshoar, Rahim
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p. 591 - 599
(2007/10/03)
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- Solvent-free synthesis of quinolone derivatives
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Quinolones can be prepared in a three step procedure from triethylorthoformate and activated methylene derivatives leading to alkoxymethylenemalonates followed by reaction with aromatic amines and finally a cyclization. All the reactions were carried out under solvent-free conditions possibly under microwave activation with benefits for the first step.
- Cernuchova, Petra,Vo-Thanh, Giang,Milata, Viktor,Loupy, Andre
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p. 177 - 191
(2007/10/03)
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- An α-hydrazinoalkylphosphonate as building block for novel N-phosphonoalkylheterocycles
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α-Hydrazinoalkylphosphonate 3 is a useful building block for the syntheses of novel N-phosphonoalkylheterocycles. N-phosphonoalkylpyrazoles 8 and 9 were prepared by the cyclization reaction of 3 with malfunctioned ethenes 5 and 6 in ethanol under reflux. N-Phosphonoalkyltriazole 10 was synthesized from 3 with N-dimethylthiomethylene benzoyl amide 4 in ethanol under reflux. The structures were confirmed by IR, 1H NMR, mass spectroscopy, and elemental analysis. At the same time, the preparation of 4 was investigated.
- Li, Zai-Guo,Sun, Hui-Kai,Wang, Qing-Min,Huang, Run-Qiu
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p. 384 - 386
(2007/10/03)
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- Synthesis of 5-Aminopyrazole-4-carbonitriles
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A one-pot reaction between substituted hydrazines, malononitrile and triethyl orthoformate leads directly to the formation of 1-substituted 5-aminopyrazole-4-carbonitriles.The scope and limitations of this synthetic procedure are discussed in relation to the well established synthesis of these compounds via substituted hydrazines and ethoxymethylenemalononitrile.
- Dooley, Michael J.,Quinn, Ronald J.,Scammells, Peter J.
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p. 747 - 750
(2007/10/02)
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- SYNTHESIS OF GLYKOSYLPYRIMIDINES ON THE BASIS OF GLYKOSYLUREA
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Acetylated derivatives of glykosylpyrimidines were synthesized on the basis of acetylated glykosylureas, malononitrile, and ethyl orthoformate.The spectral characteristics of the compounds obtained were studied.
- Grinshtein, E. E.,Liepin'sh, E. E.,Stankevich, E. I.
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p. 443 - 447
(2007/10/02)
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- Method of preparing alkoxymethylene compounds
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An improvement in the alkoxylation of a compound having a reactive methylene group by contacting said compound with an orthoformic acid trialkyl ester in the presence of a catalyst, the improvement residing in employing at least 1.6 moles of orthoformic acid ester per mole of compound having a reactive methylene group and carrying out the process in the presence of a catalyst of the group of aliphatic carboxylic acids, anhydrides of aliphatic carboxylic acids, aromatic sulphonic acids, alkali metal alcoholates and alkanolamines.
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- HETERODIENE SYNTHESES-XXIV CHANGES IN THE REACTIVITY OF 2-OXOINDOLIN-3-YLIDENE DERIVATIVES WITH ETHYLVINYLETHER INDUCED BY ELECTRON-WITHDRAWING GROUPS. THE IMPORTANCE OF THE LUMO COEFFICIENTS
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Ethylvinylether reacts in acetonitrile with 1-acetyl-2-oxoindolin-3-ylidene derivatives β,β-disubstituted with electron-withdrawing substituents.When the β-substituents act by inductive effect alone, a regiospecific β-attack occured giving rise, through a 1,4-cycloaddition, to 2,3-dihydropyranindoles.As a by product Michael adduct can be obtained.When the β-substituent act by conjugative effect also, a regiospecific α-attack occured giving rise to spiro-dihydropyrane or-cyclobutane-2-oxoindolines depending on the nature of the substituents.In a less polar solvent, the latter ones are formed together with the adduct arising from the regioisomeric β attack.The overall reactivity can be rationalized in terms of LUMO coefficients of the heterodiene and of different stabilization offered by the solvent to the various reaction pathways.
- Righetti, P. P.,Gamba, A.,Tacconi, G.,Desimoni, G.
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p. 1779 - 1785
(2007/10/02)
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