- Preparative, mechanistic and tautomeric investigation of 1-phenyl and 1-methyl derivative of 3-methyl-5-pyrazolone
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1-Phenyl and 1-methyl derivative of 3-methyl-5-pyrazolone were prepared quantitatively via a scalable solvent-free reaction of corresponding hydrazine derivative with ethyl acetoacetate. Different mechanisms have been proposed for the reaction of hydrazine derivatives (methyl or phenyl) with ethyl acetoacetate and also the tautomeric aspects of the targeted compounds have been discussed. Graphical abstract: [Figure not available: see fulltext.] Synopsis: 13C NMR and quantitative proportional amount of different tautomeric forms of 1,3-dimethyl-5-pyrazolone in DMSO-d6.
- Fakhraian, Hossein,Nafari, Yaser
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Read Online
- High chemoselectivity of C=S dipolarophile in 1,3-dipolar cycloaddition of nitrilimines and 1,2,4-triazepin-5-one derivatives: Experimental, theoretical and X-ray study
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Substituted 2,7-dimethyl-3-thioxo-3,4,5,6-tetrahydro-2H-[1,2,4]triazepin-5- one reacts as a dipolarophile with several N-aryl-C-ethoxycarbonylnitrilimines, in equimolar quantities, to give, in all cases, two types of products: diethyl 3-(p-aryl)-2-[N′-(p-aryl)-N′-(2′,7′-dimethyl-5′- oxo-5′,6′-dihydro-2H-[1,2,4]triazepin-3′-yl)-hydrazino]-2, 3-dihydro[1,3,4]thiadiazole-2,5-dicarboxylate (3a-3c in 20-25% yield) and ethyl 4-(p-aryl)-5-imino-1,4-dihydro[1,3,4]thiadiazole carboxylate (4a-4c in 45-50% yield). When 1:2 stoichiometry was used, the formation of product 3 (50%) was favoured. The reaction is entirely chemo- and regioselective. The structures of the compounds obtained, where aryl stands for p-chloro-phenyl (3b) in the first type and for tolyl (4a) in the second type, were determined by X-ray crystallography and analysed by spectral methods (NMR and mass spectroscopy). The global and local electrophilicity/nucleophilicity have been analysed to rationalize the chemical reactivity of the reactants. Copyright
- Azzouzi, Saida,El Messaoudi, Malika,Esseffar, M'hamed,Jalal, Rachid,Cano, Felix H.,Del Carmen Apreda-Rojas, Maria,Domingo, Luis R.
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Read Online
- Zeolite 4A supported CdS/g-C3N4 type-II heterojunction: A novel visible-light-active ternary nanocomposite for potential photocatalytic degradation of cefoperazone
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The CdS/g-C3N4 heterojunction photocatalyst supported on 4A zeolite was successfully synthesized using a simple chemical precipitation method. The physicochemical characteristics of the as-prepared ternary composite were assessed using X-Ray diffraction (XRD), field emission- scanning electron microscopy (FE-SEM), energy dispersive X-Ray (EDX), transmission electron microscopy (TEM), N2 adsorption–desorption, differential reflectance spectroscopy (UV–Vis-DRS), and photoluminescence (PL) techniques. The results confirmed the successful synthesis of the CdS/g-C3N4/4AZ nanocomposite and introduction of the CdS and g-C3N4 on the substrate of 4A zeolite. Cefoperazone (CFP) antibiotic was tested as the model pollutant to assess the photocatalytic performance of the synthesized nanocomposite under visible light irradiation. The response surface methodology (RSM) and artificial neural network (ANN) showed desirable reasonability for the prediction of the CFP degradation efficiency. More than 93% of CFP with a concentration of 17 mg L-1 degraded in the presence of the 0.4 g L-1 of the catalyst at pH of 9 after 80 min treatment time (RSM-based optimization results). The pH of the solution, irradiation time, catalyst dosage, and the initial concentration of the CFP affected degradation efficiency with a percentage impact of 37, 29, 19, and 15 %, respectively (ANN-based modeling results). The addition of 1 mM of isopropanol, benzoquinone, and sodium oxalate reduced the CFP degradation efficiency from 93.23% to 85.18, 41.16, and 32.47%, respectively, proving the decisive role of the °O2– and h+ in the photodegradation process. The kinetic studies indicated the following of the process from the Langmuir-Hinshelwood's pseudo-first-order model (kapp = 3.71 × 10-2 min?1). The structure of the identified by-products using GC-MS analysis confirmed that CFP mainly decomposed through the cleavage of C-S, C-N, and N-N bonds. Moreover, the formation of the aliphatic compounds and carboxylic acids as by-products confirmed nearly complete mineralization of the CFP to non-toxic products.
- AttariKhasraghi, Naime,Behnajady, Mohammad A.,Mehrizad, Ali,Modirshahla, Nasser,Zare, Karim
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- Expedient discovery for novel antifungal leads targeting succinate dehydrogenase: Pyrazole-4-formylhydrazide derivatives bearing a diphenyl ether fragment
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The pyrazole-4-carboxamide scaffold containing a flexible amide chain has emerged as the molecular skeleton of highly efficient agricultural fungicides targeting succinate dehydrogenase (SDH). Based on the above vital structural features of succinate dehydrogenase inhibitors (SDHI), three types of novel pyrazole-4-formylhydrazine derivatives bearing a diphenyl ether moiety were rationally conceived under the guidance of a virtual docking comparison between bioactive molecules and SDH. Consistent with the virtual verification results of a molecular docking comparison, the in vitro antifungal bioassays indicated that the skeleton structure of title compounds should be optimized as an N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide scaffold. Strikingly, N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide derivatives 11o against Rhizoctonia solani, 11m against Fusarium graminearum, and 11g against Botrytis cinerea exhibited excellent antifungal effects, with corresponding EC50 values of 0.14, 0.27, and 0.52 μg/mL, which were obviously better than carbendazim against R. solani (0.34 μg/mL) and F. graminearum (0.57 μg/mL) as well as penthiopyrad against B. cinerea (0.83 μg/mL). The relative studies on an in vivo bioassay against R. solani, bioactive evaluation against SDH, and molecular docking were further explored to ascertain the practical value of compound 11o as a potential fungicide targeting SDH. The present work provided a non-negligible complement for the structural optimization of antifungal leads targeting SDH.
- Chen, Min,Li, Guohua,Lu, Aimin,Qiu, Lingling,Wang, An,Wang, Xiaobin,Xue, Wei,Yang, Chunlong
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p. 14426 - 14437
(2020/12/22)
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- Metal-Free Direct C–H Thiolation and Thiocyanation of Pyrazolones
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Metal-free approach for direct C–H thiolation and thiocyanation of N-substituted pyrazolones with disulfides and thiocyanate salts, respectively, are developed. These reactions allow the C–S bond coupling to proceed effectively under mild conditions, providing useful and convenient methods for preparation of a series of 4-thio-substituted pyrazolone analogues, which have potential applications in organic, medicinal and material chemistry. Preliminary mechanistic investigation suggested that radical processes are likely to involve in these transformations.
- Kittikool, Tanakorn,Yotphan, Sirilata
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supporting information
(2020/02/13)
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- Novel 5-chloro-pyrazole derivatives containing a phenylhydrazone moiety as potent antifungal agents: synthesis, crystal structure, biological evaluation and a 3D-QSAR study
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Based on the active substructure combination principle, twenty-four novel 5-chloro-pyrazole derivatives containing a phenylhydrazone moiety were designed, synthesized, and evaluated for their antifungal activity. Their structures were confirmed using 1H NMR, 13C NMR, and HR-MS spectra. The single-crystal structure of compound 8a was analyzed emphatically using X-ray diffraction. The antifungal activities against Fusarium graminearum, Botrytis cinerea, and Rhizoctonia solani were evaluated in vitro. The results of the bioassays revealed that most of the target compounds showed obvious fungicidal activity. Strikingly, the compound 7c exhibited the most potent activity with EC50 values of 0.74, 0.68, and 0.85 μg mL?1 against the above three plant pathogenic fungi, respectively. The compounds 7c, 8d, and 8g showed significant bioactivity against R. solani with EC50 values of 0.85, 0.25, and 0.96 μg mL?1, respectively. In addition, CoMFA and CoMSIA molecular modeling was performed for a 3D-QSAR study, and presented a good predictive ability with q2 values of 0.575 and 0.667, and r2 values of 0.961 and 0.962, respectively. The results provide useful information for guiding the design and synthesis of novel potent pyrazole derivatives with good antifungal activity.
- Jiao, Jian,Wang, An,Chen, Min,Wang, Meng-Qi,Yang, Chun-Long
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p. 6350 - 6360
(2019/04/25)
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- Design of a simple and efficient synthesis for bioactive novel pyrazolyl-isoxazoline hybrids
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A simple and new methodology has been developed for the synthesis of novel bioactive pyrazolyl-isoxazoline hybrids from a pyrazolyl-substituted oxime and various substituted allyloxybenzenes, which are easily available, inexpensive starting materials. All the novel synthesized target hybrids were characterized by NMR, IR, and mass spectroscopic techniques. We have employed some of the hybrid materials in anti-bacterial and anti-fungal activity studies. The hybrid materials 6m and 6p exhibited the best anti-bacterial and anti-fungal activities.
- Sankar, Balakrishnan,Harikrishnan, Muniyasamy,Raja, Ranganathan,Sadhasivam, Velu,Malini, Nelson,Murugesan, Sepperumal,Siva, Ayyanar
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p. 10458 - 10467
(2019/07/08)
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- Method for synthesizing 1,3-dimethyl-1H-pyrazole-4-carboxylic acid
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The invention relates to a method for synthesizing 1,3-dimethyl-1H-pyrazole-4-carboxylic acid. The method comprises the step that 1,3-dimethyl-1H-pyrazole-4-carboxylic acid is prepared from the raw material: ethyl acetoacetate through condensation and ring closure, formylation, reductive dechlorination and oxidation. Compared with an existing method, the method has lower reaction cost, a higher yield and better economic performance; and the problems such as cost and environmental pollution caused by heavy metal oxidation are solved, and conditions are created for industrialization.
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Paragraph 0016; 0035; 0036; 0043-0048
(2019/11/12)
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- A new method for making pyrazole or pyrimidinone
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The invention relates to the use of an amine compound in a method for producing a fluorinated or non-fluorinated 5- or 6-membered heterocyclic compound (preferably pyrazole or pyrimidinone) containingtwo nitrogen atoms in a ring system. The invention also relates to a method for producing a pyrazole or pyrimidinone, which may be fluorinated or may not be fluorinated (non-fluorinated). Each of thefluorinated pyrazole or fluorinated pyrimidinone is a very important structural unit for pharmaceutical and agricultural applications. For example, fungicides are strongly dependent on bifenapram, fluoxastrobin, flubenazolid, fluoxastrobin, pyraclostrobin, and pyracloprid, each with this fluorinated pyrazole as a key structural unit, and benflufenazole respectively, or diflufenacil and chlorfensulfazone (dimethachlor).
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Paragraph 0306-0310
(2019/11/28)
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- Excellent antitumor and antimetastatic activities based on novel coumarin/pyrazole oxime hybrids
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A series of hybrids 10a-v based on coumarin/pyrazole oxime have been synthesized, and exhibit good to excellent antitumor activities. Compound 10n has shown remarkable anticancer effect on SMMC-7721 cells (IC50 = 2.08 μM), which is considerably lower than 5-FU (IC50 = 37.8 μM) and similar to ADM (IC50 = 2.67 μM), with little effect on normal hepatic cells LO2. Notably, the suppression experiments of metastatic activities reveal that 10n also displays significant anti-metastasis effects through inhibiting cell migration and invasion in highly metastatic SMMC-7721 cell line, and dose-dependently reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) procedure better than ADM. Finally, 10n also possesses low acute toxicity and potent tumor growth inhibitory property against SMMC-7721 cell lines in vivo. Our findings suggest that novel coumarin/pyrazole oxime hybrids are promising therapeutic agent candidates for further research.
- Dai, Hong,Huang, Meiling,Qian, Jianqiang,Liu, Ji,Meng, Chi,Li, Yangyang,Ming, Guxu,Zhang, Ting,Wang, Senling,Shi, Yujun,Yao, Yong,Ge, Shushan,Zhang, Yanan,Ling, Yong
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p. 470 - 479
(2019/02/12)
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- Design, synthesis, and biological evaluation of novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and ros in cancer cells
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Background: A large number of pyrazole derivatives have different biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity. Among them, pyrazole oximes have attracted much attention due to their potential pharmacological activities, particularly anticancer activities. Objective: Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species (ROS) accumulation in cancer cells. Methods: Eighteen bis-pyrazole oximes were synthesized by conjugating thiazolyl substituted pyrazoles with pyrazoxime. The target compounds were characterized by1HNMR,13C NMR, and HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay. The most potent compound was examined for its inhibitory effect and ROS accumulation in both cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot analysis of apoptosis-related proteins and DNA damage proteins. Results: Most compounds displayed potent antiproliferative activity against four cancer cell lines in vitro, displaying potencies superior to 5-FU. In particular, the most potent compound 13l selectively inhibited proliferation of colorectal cancer HCT116 cells but not normal colon CCD841 cells. Furthermore, compound 13l also selectively promoted intracellular ROS accumulation in HCT116 which was involved in 13l inhibition of cancer cell proliferation and induction of cell apoptosis. Finally, compound 13l also dose-dependently induced cancer cell apoptosis by regulating apoptotic and DNA damage related proteins expressions. Conclusion: Our synthetic bis-pyrazole oxime derivatives possess potent antitumor activities by selectively inducing apoptosis and ROS accumulation in cancer cells, which may hold great promise as therapeutic agents for the treatment of human cancers.
- Xiong, Biao,Chen, Shi,Zhu, Peng,Huang, Meiling,Gao, Weijie,Zhu, Rui,Qian, Jianqiang,Peng, Yanfu,Zhang, Yanan,Dai, Hong,Ling, Yong
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p. 743 - 754
(2019/11/02)
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- Pyrazolone and synthetic method of derivative of pyrazolone
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The invention relates to pyrazolone and a synthetic method of a derivative of pyrazolone. The method comprises the steps of preparing acetylacetamide with ketene dimer and ammonium hydroxide being rawmaterials in an ammoniation phase; directly adding substituted hydrazine into an ammoniation kettle to be subjected to a condensation reaction in a condensation phase; adopting concentrated hydrochloric acid to adjust the PH to promote proceeding of a ring-closure reaction in a ring-closure phase; using a cleaning solvent to conduct cleaning to obtain a purified product during aftertreatment. According to the synthetic method, a one-pot method is utilized to synthesize a pyrazolone compound free of solvents, since no solvents exist, the separation and purification process of the product are easily carried out, green production of fine chemicals is effectively achieved, the operation is convenient, the reaction time is obviously shortened, high yield of the product with excellent appearance is achieved, the product yield is increased, the product quality is improved, the yield can reach 88%-98%, and the purity can reach 96%-98%; meanwhile, drainage of wastewater is greatly reduced, andthe problems that the environment pollution is caused, the health of the human kind is harmed, and resources are wasted when water serves as a solvent are fundamentally solved.
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Paragraph 0068; 0069
(2018/03/26)
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- DABCO-catalyzed silver-promoted direct thiolation of pyrazolones with diaryl disulfides
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A highly efficient protocol for a direct thiolation of N-substituted pyrazolones with diaryl disulfides is described. Using a combination of DABCO and silver(i) acetate, the C-S bond formation proceeds smoothly at room temperature under mild and easy to handle conditions. This synthetic strategy offers a convenient and direct modification of antipyrine and other pyrazolone substrates, giving a series of aryl sulfide-substituted pyrazolone products in moderate to excellent yields.
- Thupyai, Akkharaphong,Pimpasri, Chaleena,Yotphan, Sirilata
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supporting information
p. 424 - 432
(2018/02/06)
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- Synthesis and biological activity of novel dimethylpyrazole and piperazine-containing (bis)1,2,4-triazole derivatives
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A series of novel dimethylpyrazole and piperazine-containing (bis)1,2,4-triazole derivatives have been conveniently synthesized via Mannich reaction in good yields. Their structures were identified by IR,1H NMR,13C NMR, and elemental analysis. The preliminary bioassays showed that among 14 new compounds, the trifluoromethyl-containing compounds exhibited superior activity than the methyl-containing ones; some of the compounds displayed significant in vitro and in vivo fungicidal activity against several plant fungi and were comparable with the control Triadimefon; several compounds exhibited certain herbicidal activity against Brassica campestris; several compounds possessed favorable KARI inhibitory activity, especially 8D could be a promising KARI inhibitor for further study. The research results will provide useful information for the design and discovery of new agrochemicals with novel heterocyclic Mannich base structures containing piperazine moiety.
- Wang, Bao-Lei,Zhang, Yan,Liu, Xing-Hai,Zhang, Li-Yuan,Zhan, Yi-Zhou,Zhang, Xiao,Wang, Li-Zhong,Li, Yong-Hong,Li, Zheng-Ming
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- Anti-cancer compounds targeting Ral GTPases and methods of using the same
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The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.
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Page/Page column 55; 63
(2016/06/28)
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- 4-Methylsulfonyl-Substituted Piperidine Urea Compounds
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The present invention provides novel 4-methylsulphone-substituted piperidine urea compounds that are useful for the treatment of dilated cardiomyopathy (DCM) and conditions associated with left and/or right ventricular systolic dysfunction or systolic reserve. The synthesis and characterization of the compounds is described, as well as methods for treating DCM and other forms of heart disease.
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Paragraph 0222-0223
(2016/09/26)
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- POLYCYCLIC DERIVATIVES TARGETING RAL GTPASES AND THEIR THERAPEUTICAL APPLICATIONS
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Contemplated compounds, compositions and methods are directed to Ral GTPase inhibitors with improved activity.
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Paragraph 0140-0141
(2017/01/02)
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- ANTI-CANCER COMPOUNDS TARGET RAL GTPASES AND METHODS OF USING THE SAME
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Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.
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Page/Page column 37
(2016/04/26)
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- Synthesis of novel Ral inhibitors: An in vitro and in vivo study
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Chemical synthesis was performed to produce a series of 6-amino-1,3-disubstituted-4-phenyl-1,4-dihydro pyrano[2,3-c]pyrazole-5-carbonitrile compounds (14–57) which were characterized by1H NMR,13C NMR and LC/MS–MS. These compounds were assessed for their effect on the in vitro anchorage independent growth of human lung cancer cell line H2122 and IC50values calculated. Two of the more potent compounds, BQU057 40 and BQU082 57 also displayed a dose dependent effect on RalA and RalB activity in H2122 spheroids using the common RalBP1 pull-down assay. Mouse PK and tissue distribution studies on 40 and 57 were performed and demonstrated that parent drug was present in tumor 3.0 h post ip (50 mg/Kg) dose.
- Yan, Chao,Theodorescu, Dan,Miller, Bettina,Kumar, Amit,Kumar, Vijay,Ross, David,Wempe, Michael F.
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supporting information
p. 5815 - 5818
(2016/11/25)
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- The discovery of indole derivatives as novel hepatitis C virus inhibitors
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In this study, a library of in-house small molecule was screened using a HCV cell-based assay and a compound (1) containing an N-protected indole scaffold (NINS) was identified as a novel anti-HCV inhibitor. Through structure activity relationship (SAR) study, it was observed that the racemic inhibitor (10m) displayed good anti-HCV activity (EC50 = 1.02 ± 0.10 μM) with the excellent selectivity index (SI = 45.56). Interestingly, R-enantiomer ((R)-10m) showed better anti-HCV activity and lower cytotoxicity than S-enantiomer ((S)-10m). (R)-10m gave the best anti-HCV potency (EC50 = 0.72 ± 0.09 μM) with the highest selectivity index (SI > 69.44). In addition, the mechanism of action study of NINS derivatives demonstrated that NINS derivatives interfere with the early step (viral entry) of the HCV life cycle.
- Han, Zhiqiang,Liang, Xiao,Wang, Yaxin,Qing, Jie,Cao, Lin,Shang, Luqing,Yin, Zheng
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p. 147 - 155
(2016/04/20)
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- Catch-and-release of HNO with pyrazolones
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A new and versatile class of HNO donors, the (hydroxylamino)pyrazolone (HAPY) series of HNO donors utilizing pyrazolone (PY) leaving groups, is described. HNO, the smallest N-based aldehyde equivalent, is used as a reagent along with a variety of PY compounds to synthesize the desired HAPY donors in what can be considered an N-selective HNO-aldol reaction in up to quantitative yields. The bimolecular rate constant of HNO with PY in pH 7.4 phosphate buffer at 37 °C can reach 8 × 105 M-1 s-1. In 1H NMR experiments, the HAPY compounds generate HNO quantitatively (trapped as a phosphine aza-ylide) with half-lives spanning 3 orders of magnitude (minutes to days) under physiologically relevant conditions. B3LYP/6-31G calculations confirm the energetically favorable reactions between HNO and the PY enol and enolate, whereas HNO release is expected to occur through the oxyanion (OHN-PY) of each HAPY compound. HNO has been shown to provide functional support to failing hearts.
- Guthrie, Daryl A.,Ho, Anthony,Takahashi, Cyrus G.,Collins, Anthony,Morris, Matthew,Toscano, John P.
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p. 1338 - 1348
(2015/02/19)
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- The synthesis and biological activities of [5-(4-substituted phenylsulfinyl/sulfonyl)-1,3-dimethyl-1 H-pyrazol-4-Yl]-arylmethanones
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A novel series of pyrazole derivatives containing substituted phenylsulfinyl/sulfonyl group have been synthesized via the oxidation of intermediate pyrazole sulfoether with H2O2 in acetic acid. The novel compounds were characterized by melting point, 1H NMR, FT-IR, MS, and elemental analysis or HRMS. The biological activity results showed that most of the title compounds exhibit significant fungicidal activities against Alternaria solani Sorauer, Phytophthora capsici, and Corynespora cassiicola. [Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]
- Wang, Bao-Lei,Li, Qing-Nan,Zhan, Yi-Zhou,Xiong, Li-Xia,Yu, Shu-Jing,Li, Zheng-Ming
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p. 483 - 491
(2014/04/03)
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- Discovery and characterization of small molecules that target the GTPase Ral
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The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here we used protein structure analysis and virtual screening to identify drug-like molecules that bind to a site on the GDP-bound form of Ral. The compounds RBC6, RBC8 and RBC10 inhibited the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines. The binding of the RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasmon resonance and 1 H- 15 N transverse relaxation-optimized spectroscopy (TROSY) NMR spectroscopy. RBC8 and BQU57 show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference. Our results show the utility of structure-based discovery for the development of therapeutics for Ral-dependent cancers.
- Yan, Chao,Liu, Degang,Li, Liwei,Wempe, Michael F.,Guin, Sunny,Khanna, May,Meier, Jeremy,Hoffman, Brenton,Owens, Charles,Wysoczynski, Christina L.,Nitz, Matthew D.,Knabe, William E.,Ahmed, Mansoor,Brautigan, David L.,Paschal, Bryce M.,Schwartz, Martin A.,Jones, David N.M.,Ross, David,Meroueh, Samy O.,Theodorescu, Dan
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p. 443 - 447
(2015/02/19)
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- ANTI-CANCER COMPOUNDS TARGETING RAL GTPASES AND METHODS OF USING THE SAME
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The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.
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Page/Page column 40; 52; 53
(2013/07/05)
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- Synthesis and bioactivity of pyrazole acyl thiourea derivatives
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Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3- methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3- methyl -1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, 1H-NMR, 13C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.
- Wu, Jian,Shi, Qing,Chen, Zhuo,He, Ming,Jin, Linhong,Hu, Deyu
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scheme or table
p. 5139 - 5150
(2012/07/03)
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- Condensation of N-3-substituted 5-pyrazolones with esters of β-keto acids. Synthesis of pyrano[2,3-c]pyrazol-6-ones
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N-Substituted 5-pryazolones undergo thermal condensation with esters of β-keto acids, losing water and alcohol molecules, to form N-substituted pyrano[2,3-c]pyrazol-6-ones. The pyran ring in these products is readily cleaved by the action of alkali to give the corresponding salts of unsaturated acids. 2006 Springer Science+Business Media, Inc.
- Nam,Grandberg
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p. 326 - 330
(2008/02/03)
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- Identification of antitumor activity of pyrazole oxime ethers
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A series of pyrazole oxime ether derivatives were prepared and examined as cytotoxic agents. In particular, 5-phenoxypyrazole was comparable to doxorubicin, while exhibiting very potent cytotoxicity against XF 498 and HCT15.
- Park, Hyun-Ja,Lee, Kyung,Park, Su-Jin,Ahn, Bangle,Lee, Jong-Cheol,Cho, HeeYeong,Lee, Kee-In
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p. 3307 - 3312
(2007/10/03)
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- DRUGS COMPRISING COMBINATION OF ANTITHROMBOTIC AGENT WITH PYRAZOLONE DERIVATIVE
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It is intended to provide drugs for treating and/or preventing ischemic diseases which are safe and have little side effects. Namely, drugs comprising a combination of an antithrombotic agent and a pyrazolone derivative defined in the description or its pharmaceutically acceptable salt.
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- COMPORTAMIENTO DE β-AMINOESTERES α,β-INSATURADOS FRENTE A 1,2-DINUCLEOFILOS NITROGENADOS
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The reaction of α,β-unsaturated β-aminoesters with monosubstituted hydrazines leaded to 1,3-disubstituted 5-pyrazolones, via 1,4 addition followed by elimination and cyclization of the corresponding intermediate.This behaviour is deduced from the data obtained from monotorized reactions at low temperatures or by the isolation of the intermediates in the reactions with 1,1-disubstituted hydrazines or semicarbazide.
- Alberola, A.,Calvo, L. A.,Ortega, A. Gonzalez,Sadaba, M. L.,Sanudo, M. C.
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p. 284 - 289
(2007/10/03)
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- 1,3,4-Trisubstituted-2-pyrazolin-5-one fungicides
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Novel 1,3,4-trisubstituted-2-pyrazolin-5-ones of this invention are excellent fungicides, especially against rice blast.
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