- Physicochemical properties of 4-tert-butylbenzoic acid N′,N′- dialkylhydrazides
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Properties of hydrazides of 4-tert-butylbenzoic acid, important for their application in extraction technology, have been studied: solubility, acid-base properties, distribution between immiscible liquids, and hydrolytic stability. pH ranges of existence
- Pashkina,Gusev,Radushev
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- Activity of a New Chromium(III) Complex with a Pentadentate (N3O2) Schiff-Base Ligand in the Reaction of Carbon Dioxide with Propylene Oxide
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Abstract: The reaction of carbon dioxide with propylene oxide was carried out in the presence of a new pentadentate chromium complex, dichloro[2,6-diacetylpyridine bis(4-tert-butylbenzoylhydrazone)]chromium(III). The reaction kinetics was studied under different reaction conditions (temperature, pressure, and catalyst concentration). Optimal conditions for the synthesis of cyclic carbonate in the presence of the new chromium complex were found. The effective activation energy of the formation of cyclic carbonate was determined. The catalyst activity significantly depended on the substituent R in a 2,6-diacetylpyridine bis(4-R-benzoylhydrazone) ligand.
- Bazhenova, T. A.,Chukanova, O. M.,Kornev, A. B.,Manakin, Yu. V.,Sedov, I. V.,Sheverdenkina, O. G.,Yakushev, I. A.
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p. 428 - 435
(2021/06/14)
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- Design, synthesis, and biological evaluation of phenyloxadiazole derivatives as potential antifungal agents against phytopathogenic fungi
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Abstract: A novel series of picarbutrazox-inspired oxadiazole hybrids was synthesized and the derivatives’ biological activity against phytopathogenic fungi was investigated. The molecules were designed by retaining the active fragment of tetrazolyl phenyloxime ether of lead compound picarbutrazox, while introducing the potentially active oxadiazole-derived fragment. Bioassay results revealed that some of the title compounds showed potent in vivo antifungal activities to control cucumber downy mildew. Therefore, this novel oxadiazole phenyloxadiazole derivative can be used as a potential antifungal agent to control cucumber downy mildew and other phytopathogenic fungi for crop protection. Graphic abstract: [Figure not available: see fulltext.].
- Li, Yitao,Yao, Wenqiang,Lin, Jian,Gao, Guoliang,Huang, Chang,Wu, Yang
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p. 121 - 135
(2021/01/05)
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- Essential oil-based design and development of novel anti-Candida azoles formulation
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Candida is the most common fungal class, causing both superficial and invasive diseases in humans. Although Candida albicans is the most common cause of fungal infections in humans, C. auris is a new emergent serious pathogen causing complications similar to those of C. albicans. Both C. albicans and C. auris are associated with high mortality rates, mainly because of their multidrug-resistance patterns against most available antifungal drugs. Although several compounds were designed against C. albicans, very few or none were tested on C. auris. Therefore, it is urgent to develop novel effective antifungal drugs that can accommodate not only C. albicans, but also other Candida spp., particularly newly emergent one, including C. auris. Inspired by the significant broad-spectrum antifungal activities of the essential oil cuminaldehyde and the reported wide incorporation of azoles in the antifungal drugs, a series of compounds (UoST1-11) was designed and developed. The new compounds were designed to overcome the toxicity of the aldehyde group of cuminaldehyde and benefit from the antifungal selectivity of azoles. The new developed UoST compounds showed significant anti-Candida activities against both Candida species. The best candidate compound, UoST5, was further formulated into polymeric nanoparticles (NPs). The new formula, UoST5-NPs, showed similar activities to the nanoparticles-free drug, while providing only 25% release after 24 h, maintainng prolonged activity up to 48 h and affording no toxicity. In conclusion, new azole formulations with significantly enhanced activities against C. albicans and C. auris, while maintaining prolonged action and no toxicities at lower concentrations, were developed.
- Fayed, Bahgat,Haider, Mohamed,Hamdy, Rania,Hamoda, Alshaimaa M.,Rawas-Qalaji, Mutasem,Soliman, Sameh S. M.
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- Selective inhibition of Rhizopus eumelanin biosynthesis by novel natural product scaffold-based designs caused significant inhibition of fungal pathogenesis
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Melanin is a dark color pigment biosynthesized naturally in most living organisms. Fungal melanin is a major putative virulence factor of Mucorales fungi that allows intracellular persistence by inducing phagosome maturation arrest. Recently, it has been shown that the black pigments of Rhizopus delemar is of eumelanin type, that requires the involvement of tyrosinase (a copper-dependent enzyme) in its biosynthesis. Herein, we have developed a series of compounds (UOSC-1-14) to selectively target Rhizopus melanin and explored this mechanism therapeutically. The compounds were designed based on the scaffold of the natural product, cuminaldehyde, identified from plant sources and has been shown to develop non-selective inhibition of melanin production. While all synthesized compounds showed significant inhibition of Rhizopus melanin production and limited toxicity to mammalian cells, only four compounds (UOSC-1, 2, 13, and 14) were selected as promising candidates based on their selective inhibition to fungal melanin. The activity of compound UOSC-2 was comparable to the positive control kojic acid. The selected candidates showed significant inhibition of Rhizopus melanin but not human melanin by targeting the fungal tyrosinase, and with an IC50 that are 9 times lower than the reference standard, kojic acid. Furthermore, the produced white spores were phagocytized easily and cleared faster from the lungs of infected immunocompetent mice and from the human macrophages when compared with wild-type spores. Collectively, the results suggested that the newly designed derivatives, particularly UOSC-2 can serve as promising candidate to overcome persistence mechanisms of fungal melanin production and hence make them accessible to host defenses.
- Soliman, Sameh S.M.,Hamdy, Rania,Elseginy, Samia A.,Gebremariam, Teclegiorgis,Hamoda, Alshaimaa M.,Madkour, Mohamed,Venkatachalam, Thenmozhi,Ershaid, Mai N.,Mohammad, Mohammad G.,Chamilos, Georgios,Ibrahim, Ashraf S.
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p. 2489 - 2507
(2020/09/02)
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- Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
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Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
- Alves, Marina A.,Chaves, Lorrane S.,Fernandes, Patrícia D.,Fraga, Carlos A. M.,Guerra, Fabiana S.,Rodrigues, Daniel A.,Sagrillo, Fernanda S.,Sant'Anna, Carlos M. R.,Thota, Sreekanth,de Sena M. Pinheiro, Pedro
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supporting information
(2020/02/25)
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- Discovery of [1,2,4]triazole derivatives as new metallo-β-lactamase inhibitors
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The emergence and spread of metallo-β-lactamase (MBL)-mediated resistance to β-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse β-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 μM. Investigations of 5l against other B1 MBLs and the serine β-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.
- Yuan, Chen,Yan, Jie,Song, Chen,Yang, Fan,Li, Chao,Wang, Cheng,Su, Huiling,Chen, Wei,Wang, Lijiao,Wang, Zhouyu,Qian, Shan,Yang, Lingling
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- A novel one-pot synthesis method of 3,4,5-triaryl-substituted 1,2,4-triazoles
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[Figure not available: see fulltext.] A novel method for the preparation of 3,4,5-triaryl-substituted 1,2,4-triazoles by the reaction of hydrazides with secondary amides in polyphosphoric ester has been developed. The new method is characterized by mild conditions and ease of synthesis, including the stages of isolation and purification of the product. Additionally, product structures were confirmed by counter synthesis. It was shown that the proposed method is suitable for producing 1,2,4-triazoles with phenolic substituents without the stages of the protection and deprotection of the hydroxyl group. Using the new method, five 3,4,5-substituted 1,2,4-triazoles were obtained for the first time.
- Yakuschenko, Igor K.,Pozdeeva, Natal’ya N.,Gadomsky, Svyatoslav Ya.
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p. 834 - 838
(2019/11/14)
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- TBSOTf-promoted versatile N-formylation using DMF at room temperature
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Hydrazides and amines were N-formylated by DMF in the presence of tert-butyldimethylsilyl triflate (TBSOTf) at room temperature, in good to excellent yields.
- Sakurai, Masayoshi,Kawakami, Rina,Kihara, Nobuhiro
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supporting information
p. 1291 - 1294
(2019/04/10)
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- Discovery of 1,3,4-oxadiazol-2-one-containing benzamide derivatives targeting FtsZ as highly potent agents of killing a variety of MDR bacteria strains
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The spread of infections caused by multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), has created a need for new antibiotics with novel mechanisms of action. The bacterial division protein FtsZ has been identified as a novel drug target that can be exploited clinically. As part of an ongoing effort to develop FtsZ-targeting antibacterial agents, we describe herein the design, synthesis and bioactivity of six series of novel 1,3,4-oxadiazol-2-one-containing, 1,2,4-triazol-3-one-containing and pyrazolin-5-one-containing benzamide derivatives. Among them, compound A14 was found to be the most potent antibacterial agent, much better than clinical drugs such as ciprofloxacin, linezolid and erythromycin against all the tested gram-positive strains, particularly methicillin-resistant, penicillin-resistant and clinical isolated S. aureus. Subsequent studies on biological activities and docking analyses proved that A14 functioned as an effective compound targeting FtsZ. Preliminary SAR indicated a general direction for further optimization of these novel analogues. Taken together, this research provides a promising chemotype for developing newer FtsZ-targeting bactericidal agents.
- Bi, Fangchao,Song, Di,Qin, Yinhui,Liu, Xingbang,Teng, Yuetai,Zhang, Na,Zhang, Panpan,Zhang, Nan,Ma, Shutao
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p. 3179 - 3193
(2019/06/17)
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- Dithiocarbamate as a valuable scaffold for the inhibition of metallo-β-lactmases
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The ‘superbug’ infection caused by metallo-β-lactamases (MβLs) has grown into an emergent health threat. Given the clinical importance of MβLs, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited MβLs NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC50 50 0.22 μM). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against E. coli-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of E. coli cells, expressing the three MβLs, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 μM, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 μM. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of MβLs inhibitors.
- Ge, Ying,Xu, Li-Wei,Liu, Ya,Sun, Le-Yun,Gao, Han,Li, Jia-Qi,Yang, Kewu
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- Synthesis and antitumor evaluation of novel fused heterocyclic 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives
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In this study, twenty three 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were synthesized and their antiproliferative activities in vitro were studied against SMMC-7721, HeLa, A549, and L929 by the CCK-8 assay. The bioassay results demonstrated that all tested compounds 8(a–w) exhibited antiproliferation with different degrees, and some compounds showed better effects than reference drug 5-fluorouracil. Among these screened compounds, compounds 8a, 8d, and 8l displayed significant antitumor activities in inhibiting SMMC-7721cell proliferation with IC50 values of 1.64, 1.74, and 1.61 μM, respectively. Compounds 8d and 8l were manifested highly effective biological activity versus HeLa cells with IC50 values of 2.23 and 2.84 μM, respectively. Compound 8l was found to have the highest antitumor potency against A549 cells with IC50 value of 2.67 μM. Furthermore, all compounds exhibited weaker cytotoxic effects than 5-fluorouracil on normal cell lines L929.
- Liu, Xiao-Jia,Liu, Hai-Ying,Wang, Hai-Xin,Shi, Yan-Ping,Tang, Rui,Zhang, Shuai,Chen, Bao-Quan
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p. 1718 - 1725
(2019/08/02)
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- Rapid and Atom Economic Synthesis of Isoquinolines and Isoquinolinones by C–H/N–N Activation Using a Homogeneous Recyclable Ruthenium Catalyst in PEG Media
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Herein, we report an atom-efficient, rapid, green, and sustainable approach to synthesize isoquinolines and isoquinolinones using a homogeneous recyclable ruthenium catalyst in PEG Media assisted by microwave energy. Dibenzoylhydrazine was used for C–H/N–N activation reactions for the first time in combination with ketazine as oxidizing directing groups for annulation reactions with internal alkynes. The developed protocol is environmentally benign due to significantly shortened times with an easy extraction method, higher atom economy, external oxidant and silver or antimony salt free conditions, applicability to a gram scale synthesis, use of biodegradable solvent and wide substrate scope with higher product yields. Moreover, it is worth noting that the established methodology allowed reuse of the catalytic system for up to five successive runs with minimal loss in activity.
- Deshmukh, Dewal S.,Gangwar, Neha,Bhanage, Bhalchandra M.
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supporting information
p. 2919 - 2927
(2019/05/10)
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- Synthesis of α-aminocarbonyl compounds via hetero dielsalder reaction
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A synthetic route to α-aminoketone derivatives via a hetero DielsAlder reaction is described. Diacylhydrazine was oxidized by tert-butyl hypochlorite in the presence of pyridine. After evaporation, the hetero DielsAlder reaction with diene was carried out without isolation of the azodicarbonyl compound. Quantitative hetero DielsAlder reaction was possible with 1 equivalent of diene when Hf(OTf)4 or AgOTf was used as the catalyst. The NN bond of the product was cleaved by SmI2-reduction in the presence of tert-BuOH in THF. Further, ozonolysis of the C=C double bond afforded the α-aminoketone derivative in excellent yield.
- Sakurai, Masayoshi,Kihara, Nobuhiro,Watanabe, Nobuhiro,Ikari, Yoshihiro,Takata, Toshikazu
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supporting information
p. 144 - 147
(2018/01/01)
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- Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents
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4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
- Meira, Cássio S.,dos Santos Filho, José Maurício,Sousa, Caroline C.,Anjos, Pamela S.,Cerqueira, Jéssica V.,Dias Neto, Humberto A.,da Silveira, Rafael G.,Russo, Helena M.,Wolfender, Jean-Luc,Queiroz, Emerson F.,Moreira, Diogo R.M.,Soares, Milena B.P.
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p. 1971 - 1985
(2018/03/12)
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- Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives
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Background: Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation. Subsequently, the synthesis of effective chemotherapeutic agents that can induce apoptosis in tumor cell has emerged as a significant approach in cancer drug discovery. Methods: The goal of this work is to develop a potential antitumor agent exerting significant inhibitory effects on cancer cell and low cytotoxicity, for which we focused on the structural features of 1,3,4-oxadiazoles as it a privileged scaffold in modern medicinal chemistry and have the ability to inhibit growth factors, enzymes and kinases potentially involved in the attainment of cellular immortality and carcinogenesis. Result: In vitro MTT screening assay showed the compound 5-aminophenyl-2-butylthio-1,3,4-oxadiazole (5e) showing the highest inhibitory effect against MCF-7 cancer cell with IC50 value 10.05?±?1.08?μM while it is much safer and less toxic on normal cell line (HEK-293). The dose-dependent treatment of MCF-7 cells with 5e resulted in inhibition of cell migration in the wound healing assay. The flow-cytometry analysis showed the cells arrested in G0/G1 phase of the cell cycle. Compound 5e induced apoptosis of MCF-7 cells was characterized using DAPI staining and Annexin V-PE/7-AAD dual binding assay. Reduction of NBT by compound 5e showed a reduced generation of ROS. Western blotting studies showed high activation of apoptotic protein Caspase3 and decrease in expression of anti-apoptotic protein BCL-2. Conclusion: Based on the results of in vitro studies, it could be concluded that compound 5e showed a significant inhibitory growth effect on MCF-7 cells and have the potential to be developed as lead molecule and further structural modifications may result in promising new anticancer agents.
- Khanam, Rashmin,Ahmad, Kamal,Hejazi, Iram I.,Siddique, Ibrar A.,Kumar, Vikash,Bhat, Abdul Roouf,Azam, Amir,Athar, Fareeda
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p. 1027 - 1042
(2017/10/06)
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- Based on 4,4 the structure of the- [...][...] 9, the 9-bit [...] a main body material and its application (by machine translation)
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Based on 4,4 the structure of the- [...][...] 9, the 9-bit [...] a main body material and its application, the present invention discloses a kind HOMO line condition and at the same time has a high level and the main material with excellent performance, its to 4, the 4-bit connected [...][...] as the molecule skeleton structure, in its 9,9 the connecting substituent [...] -position, which can be connected with transmission performance of the cavity diphenylammonium unit Dn, but also can be connected with electronic transmission performance unit An: phosphorusoxychloride unit, sulfur and oxygen unit, in addition to the two special spiral ring-like structure can be formed. The main body material of the present invention synthetic method is simple and easy to operate, which is suitable to be widely used. Main body material by the present invention of the organic electroluminescent light-emitting device is phosphorescent blue light, has high efficiency, high brightness, low efficiency low starting voltage attenuation and electroluminescent performance, can be widely applied to the organic electroluminescent field. (by machine translation)
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Paragraph 0059; 0060
(2016/10/10)
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- Hydrazide-hydrazones of 3-methoxybenzoic acid and 4-tert-butylbenzoic acid with promising antibacterial activity against Bacillus spp
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A series of 28 hydrazide-hydrazones of 3-methoxybenzoic and 4-tert-butylbenzoic acid were synthesized and screened in vitro against the panel of reference strains of bacteria and fungi with the use of the broth microdilution method according to EUCAST and CLSI guidelines. Five of the synthesized compounds were found to exhibit high bacteriostatic or bactericidal activity against Gram-positive bacteria. The antimicrobial activity of compounds 13, 14, and 16 against Bacillus spp. was higher than that of commonly used antibiotics, like cefuroxime or ampicillin.
- Popio?ek, ?ukasz,Biernasiuk, Anna
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- An efficient nonconventional glycerol-based solid acid catalyzed synthesis and biological evaluation of phosphonate conjugates of 1,2,4-triazole thiones
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A series of diethyl (3-((5-aryl-1H-1,2,4-triazol-3-yl)thio)propyl)phos-phonates (7a-t) has been synthesized in excellent yields by coupling diethyl (3-bromopropyl)phosphonate and 5-aryl-1H- 1,2,4-triazol-3-thiones employing an efficient, green and nonconventional heterogeneous SO3Hcarbon catalyst derived from glycerol. In addition, a facile and green approach for the esterification of carboxylic acids by utilizing glycerol-based solid acid catalyst has been reported. Structures of the synthesized compounds were characterized by IR, NMR and HRMS studies. These triazole derivatives were screened for their in vitro cytotoxicity using the standard MTT (3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide) assay against a panel of five different human cancer cell lines (HeLa: Cervix, A549: Lung, A375: Skin, MDA-MB-231: Breast and T98G: Brain). The antimicrobial activities of the synthesized compounds were investigated against four bacterial strains: Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and three fungal strains: Aspergillus Niger, Aspergillus terreus, Aspergillus fumigatus. Preliminary results indicate that the compound 7f displayed maximum anticancer activity and the compounds 7d, 7e, 7f, 7m and 7q exhibited moderate antibacterial activity. The compounds 7g, 7h, 7o and 7p showed good antifungal activity with high inhibition zone diameter compared to the standard drug.
- Murty, Madugula S.R.,Katiki, Mohana R.,Rao, Busam R.,Narayanan, Sai S.,Anto, Ruby J.,Buddana, Sudhreer K.,Prakasham, Reddy S.,Devi, Bethala L.A.P.,Prasad, Rachapudi B.N.
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p. 968 - 981
(2016/10/31)
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- Designing and exploring active N′-[(5-nitrofuran-2-yl) methylene] substituted hydrazides against three Trypanosoma cruzi strains more prevalent in Chagas disease patients
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Chagas disease affects around 8 million people worldwide and its treatment depends on only two nitroheterocyclic drugs, benznidazole (BZD) and nifurtimox (NFX). Both drugs have limited curative power in chronic phase of disease. Nifuroxazide (NF), a nitroheterocyclic drug, was used as lead to design a set of twenty one compounds in order to improve the anti-Trypanosoma cruzi activity. Lipinski's rules were considered in order to support drug-likeness designing. The set of N′-[(5-nitrofuran-2-yl) methylene] substituted hydrazides was assayed against three T. cruzi strains, which represent the discrete typing units more prevalent in human patients: Y (TcII), Silvio X10 cl1 (TcI), and Bug 2149 cl10 (TcV). All the derivatives, except one, showed enhanced trypanocidal activity against the three strains as compared to BZD. In the Y strain 62% of the compounds were more active than NFX. The most active compound was Ng€2-((5-nitrofuran-2-yl) methylene)biphenyl-4-carbohydrazide (C20), which showed IC50 values of 1.17 ± 0.12 μM; 3.17 ± 0.32 μM; and 1.81 ± 0.18 μ4M for Y, Silvio X10 cl1, and Bug 2149 cl10 strains, respectively. Cytotoxicity assays with human fibroblast cells have demonstrated high selectivity indices for several compounds. Exploratory data analysis indicated that primarily topological, steric/geometric, and electronic properties have contributed to the discrimination of the set of investigated compounds. The findings can be helpful to drive the designing, and subsequently, the synthesis of additional promising drugs against Chagas disease.
- De Azevedo, Ricardo Alexandre,Ferreira, Adilson Kleber,Jorge, Salomo Dria,Palace-Berl, Fanny,Pasqualoto, Kerly Fernanda Mesquita,Silva, Marcelo Nunes,Tavares, Leoberto Costa,Teixeira, Sarah Fernandes,Zingales, Bianca,Zorzi, Rodrigo Rocha
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p. 330 - 339
(2015/04/27)
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- Synthesis and evaluation of some substituted heterocyclic fluconazole analogues as antifungal agents
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A new series of fluconazole analogues of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4- difluoro-phenyl)-3-4-(substituted-heterocyclic ring-1H-1,2,3- triazol-1-yl)-2-propanols (1-10) were designed, synthesized and evaluated as antifungal agents. Preliminary antifungal tests showed that most of the title compounds exhibited moderate activity with broad spectrum against eight human pathogenic fungi in vitro, compounds 1 and 6 had the best antifungal activity against Candida albicans with the value of MIC80 = 0.5 μg/mL respectively.
- Wang, Shudong,Zhang, Lei,Jin, Yongsheng,Tang, Jin Hao,Su, Hua,Yu, Shichong,Ren, Haixiang
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p. 2362 - 2364
(2014/06/09)
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- Magnetically Recyclable Nano-Fe 2O 3-Catalyzed Chemoselective Synthesis and Antioxidant Activity of Diethyl (3-((5-Aryl-1 H-1,2,4-triazol-3-yl)thio)propyl) phosphonates
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An efficient, green, and chemoselective S-alkylation of 5-aryl-1H-1,2,4-triazole-3-thiones with diethyl (3-bromopropyl)phosphonate in water, catalyzed by nano-Fe2O3 under ligand-and base-free conditions, is reported. Clean reaction, less expensive catalyst, excellent yields, and easy workup are the advantages of the present method. The catalyst can be easily collected by a magnet and recycled without significant loss in catalytic activity. The newly synthesized compounds were screened for their antioxidant property by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay. The majority of the compounds exhibited good antioxidant activity.
- Murty,Katiki, Mohana Rao,Rao, B. Ramalingeswara,Nanubolu, Jagadeesh Babu,Buddana, Sudheer Kumar,Prakasham
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p. 2724 - 2737
(2014/08/18)
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- Synthesis and antifungal activity of substituted salicylaldehyde hydrazones, hydrazides and sulfohydrazides
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Efficient synthetic procedures for the preparation of acid hydrazines and hydrazides were developed by converting the corresponding carboxylic acid into the methyl ester catalyzed by Amberlyst-15, followed by a reaction with hydrazine monohydrate. Sulfohydrazides were prepared from the corresponding sulfonyl chlorides and hydrazine monohydrate. Both of these group of compounds were condensed with substituted salicylaldehydes using gradient concentration methods that generated a large library of hydrazone, hydrazide and sulfohydrazide analogs. Antifungal activity of the prepared analogs showed that salicylaldehyde hydrazones and hydrazides are potent inhibitors of fungal growth with little to no mammalian cell toxicity, making these analogs promising new targets for future therapeutic development.
- Backes, Gregory L.,Neumann, Donna M.,Jursic, Branko S.
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p. 4629 - 4636
(2014/11/08)
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- Synthesis and antimicrobial properties of 1,3,4-oxadiazole analogs containing dibenzosuberane moiety
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A series of ten novel 1,3,4-oxadiazole analogs containing dibenzosuberane moiety were synthesized using linear as well as convergent synthesis approach. All the compounds were characterized by mass spectrometry, infrared (IR), 1H and 13C nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopies and elemental analysis. These compounds were evaluated for antibacterial and antifungal activities. Among ten analogs, four compounds, namely, 8a, 8d, 8e and 8j were found to be highly active antibacterial and antifungal agents.
- Moger, Manjunath,Satam, Vijay,Govindaraju, Darshan Raj C.,Paniraj,Gopinath, Vadiraj S.,Hindupur, Rama Mohan,Pati, Hari N.
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p. 104 - 111
(2014/02/14)
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- Immobilization of styrene-substituted 1,3,4-oxadiazoles into thermoreversible luminescent organogels and their unexpected photocatalyzed rearrangement
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A series of styrene-substituted 1,3,4-oxadiazoles has been designed and investigated as new low-molecular-weight organogelators. The photophysical properties of the resulting thermoreversible organogels have been characterized by UV/Vis absorption and luminescence spectroscopies. Surprisingly, the gelation ability of the oxadiazoles depended on the presence of the styrene moiety as gelation of the investigated oxadiazoles did not take place in its absence. Gel formation was accompanied by a modification of the fluorescence of the organogelators in the supramolecular state. UV irradiation of the gels caused a rearrangement of the immobilized 1,3,4-oxadiazoles bearing a styrene moiety by a tandem [4+2] and [3+2] cascade reaction. Structure modification and color change of the gels were also evident upon irradiation. Copyright
- Dumur, Frederic,Contal, Emmanuel,Wantz, Guillaume,Phan, Trang N. T.,Bertin, Denis,Gigmes, Didier
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supporting information
p. 1373 - 1384
(2013/03/13)
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- Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents
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A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.
- Du, Qian-Ru,Li, Dong-Dong,Pi, Ya-Zhou,Li, Jing-Ran,Sun, Jian,Fang, Fei,Zhong, Wei-Qing,Gong, Hai-Bin,Zhu, Hai-Liang
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p. 2286 - 2297
(2013/05/09)
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- Synthesis and insecticidal activities of cis-configuration nitenpyram analogues with benzoyl hydrazines
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To research on the structure-activity relationships of our designed neonicotinoid compounds, a series of novel cis-configuration nitenpyram analogues with benzoyl hydrazines were designed and synthesized. The structures of all compounds were confirmed by IR, 1H NMR, MS, and elemental analysis. Preliminary bioassays indicated that all the analogues exhibited good insecticidal activities against Nilaparvata legen and Aphis medicagini at 500 mg L-1.
- Xu, Xiao,Sun, Chuan-Wen,Yang, Ding-Rong,Bu, Hong-Fei,Wang, Jing,Xu, Yong-Hua
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p. 945 - 948
(2013/08/23)
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- Ligand-based design, synthesis, and experimental evaluation of novel benzofuroxan derivatives as anti-Trypanosoma cruzi agents
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A set of substituted-[N′-(benzofuroxan-5-yl)methylene]benzohydrazides (4a-t), previously designed and synthesized, was experimentally assayed against Trypanosoma cruzi, the etiological agent of Chagas' disease, one of the most neglected tropical diseases. Exploratory data analysis, Hansch approach and VolSurf formalism were applied to aid the ligand-based design of novel anti-T. cruzi agents. The best 2D-QSAR model showed suitable statistical measures [n = 18; s = 0.11; F = 42.19; R2 = 0.90 and Q2 = 0.77 (SDEP = 0.15)], and according to the optimum 3D-QSAR model [R2 = 0.98, Q 2 = 0.93 (SDEP = 0.08)], three latent variables explained 62% of the total variance from original data. Steric and hydrophobic properties were pointed out as the key for biological activity. Based upon the findings, six novel benzofuroxan derivatives (4u-z) were designed, synthesized, and in vitro assayed to perform the QSAR external prediction. Then, the predictability for the both models, 2D-QSAR (Rpred2 = 0.91) and 3D-QSAR (Rpred2 = 0.77), was experimentally validated, and compound 4u was identified as the most active anti-T. cruzi hit (IC50 = 3.04 μM).
- Jorge, Salom?o Dória,Palace-Berl, Fanny,Mesquita Pasqualoto, Kerly Fernanda,Ishii, Marina,Ferreira, Adilson Kleber,Berra, Carolina Maria,Bosch, Rosemary Viola,Maria, Durvanei Augusto,Tavares, Leoberto Costa
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p. 200 - 214
(2013/07/27)
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- Synthesis of new S-alkylated-3-mercapto-1,2,4-triazole derivatives bearing cyclic amine moiety as potent anticancer agents
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A series of 3-[3-[4-(Substituted)-1-cyclicamine]propyl]thio-5- substituted[1,2,4]triazoles (8a-j) were synthesized with good yields starting from corresponding carboxylic acids. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Three compounds had shown good anticancer activity. The triazole derivatives, 8i and 8j were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinants of their biological activity.
- Murty,Ram, Kesur R.,Rao, Rayudu Venkateswara,Yadav,Rao, Janapala Venkateswara,Pamanji,Velatooru
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experimental part
p. 276 - 281
(2012/06/18)
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- Synthesis, biological evaluation and molecular docking studies of novel 2-(1,3,4-oxadiazol-2-ylthio)-1-phenylethanone derivatives
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In present study, a series of new 2-(1,3,4-oxadiazol-2-ylthio)-1- phenylethanone derivatives (6a-6x) as potential focal adhesion kinase (FAK) inhibitors were synthesized. The bioassay assays demonstrated that compound 6i showed the most potent activity, which inhibited the growth of MCF-7 and A431 cell lines with IC50 values of 140 ± 10 nM and 10 ± 1 nM, respectively. Compound 6i also exhibited significant FAK inhibitory activity (IC50 = 20 ± 1 nM). Docking simulation was performed to position compound 6i into the active site of FAK to determine the probable binding model.
- Zhang, Li-Rong,Liu, Zhi-Jun,Zhang, Hui,Sun, Jian,Luo, Yin,Zhao, Ting-Ting,Gong, Hai-Bin,Zhu, Hai-Liang
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scheme or table
p. 3615 - 3621
(2012/07/27)
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- WHITE-EMITTING COMPOUNDS USING EXCITED-STATE INTRAMOLECULAR PROTON TRANSFER, ORGANIC ELECTROLUMINESCENT ELEMENT AND LASER MATERIAL USING THE SAME
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Provided are a white-emitting monomolecular compound using excited-state intramolecular proton transfer (ESIPT) characteristics, and an organic electroluminescence device and a laser device comprising same. The white-emitting monomolecular compound according to the present invention is prepared by covalently bonding at least two types of molecules which produce different colors and have excited-state intramolecular proton transfer (ESIPT) characteristics. The white-emitting monomolecular compound according to the present invention achieves white luminescence irrespective of the concentration thereof and of the state of the materials thereof, and therefore can be used in a variety of fields including an organic electroluminescence device and a laser device.
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Page/Page column 10
(2012/03/10)
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- Synthesis and insecticidal activities of 1,3,5-trisubstituted-1,3,5- hexahydrotriazine-2-N-nitroimines
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A new series of 1,3,5-trisubstituted-1,3,5-hexahydrotriazine-2-N- nitroimines (3a-3j) were designed and synthesized as novel neonicotinoid analogues, and their structures were characterized by 1H NMR, IR, elemental analysis and MS. The preliminary bioassay tests showed that most of the target compounds had good insecticidal activities against Nilaparvata lugens as well as Aphis medicaginis at 500 mg/L, while compound 3i had 100% mortality against Nilaparvata lugens at 20 mg/L.
- Xue, Sijia,Ma, Xubo,Bu, Hongfei,Liu, Li,Xu, Xiao
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p. 2153 - 2156
(2012/03/26)
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- Development and assessment of green synthesis of hydrazides
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An expeditious, solvent free one pot method for the preparation of hydrazides from corresponding acids directly under microwave irradiation is developed. The method has been assessed using green chemistry measures and found superior to conventional method with higher E(environmental) factor, atom economy, atom efficiency, carbon efficiency, reaction mass efficiency.
- Saha, Ajoy,Kumar, Rajesh,Kumar, Rajendra,Devakumar
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experimental part
p. 526 - 531
(2010/10/03)
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- Green synthesis of 5-substituted-1,3,4-thiadiazole-2-thiols as new potent nitrification inhibitors [1]
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(Chemical Equation Presented) A fast, efficient synthesis of 5-substituted-1,3,4-thiadiazole-2-thiols was successfully developed, assessed using green chemistry matrices, and compounds were screened for their in vitro nitrification inhibitory activity. The greener method was superior with higher energy efficiency, E(nvironmental) factor, atom economy, atom efficiency, carbon efficiency, and reaction mass efficiency.
- Saha, Ajoy,Kumar, Rajesh,Kumar, Rajendra,Devakumar
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experimental part
p. 838 - 845
(2010/10/04)
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- ROMP-POLYMERIZABLE ELECTRON TRANSPORT MATERIALS BASED ON A BIS-OXADIAZOLE MOIETY
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This invention relates generally to a solution processable norbornene monomer, poly(norbornene) homopolymer, and poly(norbornene) copolymer compounds containing a functionalized bis -oxadiazole side chain, and to an electron injecting/transporting layer, a hole -blocking layer, or an emissive material, organic electronic devices and compositions which include these compounds.
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Page/Page column 25
(2009/07/25)
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- PTEN INHIBITORS
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The therapeutic use of inhibitors of PTEN activity in the treatment of PTEN-mediated diseases, conditions, and injuries is disclosed.
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Page/Page column 70-71
(2008/06/13)
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- Study of the acylation reaction of 2,6-dimethyl-3,5-pyridinedicarboxylic acid hydrazides
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Acylation of 3-ethoxycarbonyl-2,6-dimethyl-5-pyridinecarboxylic acid hydrazide and 2,6-dimethyl-3,5-pyridinedicarboxylic acid dihydrazide using aromatic acid chlorides gave the corresponding N-aroyl hydrazides. It was found that the hydrazinolysis of 3-ethoxycarbonyl-2,6-dimethyl-5-pyridine-dicarboxylic acid N-aroyl hydrazides occurred not at the ester group but as a rehydrazinolysis reaction at the dihydrazide fragment. 2005 Springer Science+Business Media, Inc.
- Nesterova,Voevudsky,Samukha,Zubatyuk,Shishkin
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p. 1511 - 1520
(2007/10/03)
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- Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3
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A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P1) receptor agonists with minimal affinity for the S1P2 and S1P3 receptor subtypes. Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy.
- Li, Zhen,Chen, Weirong,Hale, Jeffrey J.,Lynch, Christopher L.,Mills, Sander G.,Hajdu, Richard,Keohane, Carol Ann,Rosenbach, Mark J.,Milligan, James A.,Shei, Gan-Ju,Chrebet, Gary,Parent, Stephen A.,Bergstrom, James,Card, Deborah,Forrest, Michael,Quackenbush, Elizabeth J.,Wickham, L. Alexandra,Vargas, Hugo,Evans, Rose M.,Rosen, Hugh,Mandala, Suzanne
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p. 6169 - 6173
(2007/10/03)
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- BLUE LIGHT-EMITTING COMPOUND, METHOD FOR PRODUCING SAME AND LIGHT-EMITTING DEVICE UTILIZING SAME
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The present invention provides blue-light emitting compounds capable of emitting blue light at a high luminance for a long time upon the application of electric energy, processes of producing the compounds, and luminescent elements including the blue light-emitting compounds. One of the compounds according to the present invention is characterized by the chemical structure represented by formula (1).
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Page/Page column 26
(2008/06/13)
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- Synthesis and electrooptical properties of novel PPV derivatives containing 1,3,4-oxadiazole
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Poly[2-{5′-(4″-t-butylphenyl)-1′, 3′, 4′-oxadiazole}-1,4-phenylenevinylene (BPOD-PPV)] containing 4-t-butylphenyl-1,3,4-oxadiazole pendant was synthesized by Gilch reaction. The obtained polymer shows a strong absorption centered around 300nm and broader peak at about 350-520 nm. The efficiency of ITO/ PPV/polymer/Al device is greater than by more than 2 orders of magnitude when compared with the ITO/PPV/Al device.
- Kim, Yun-Hi,Shin, Dong-Cheol,Jung, Sung-Ouk,Kwon, Soon-Ki,Hwang, Do-Hoon
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- Branched chain amino acid-dependent aminotransferase inhibitors and their use in the treatment of neurodegenerative diseases
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The invention relates to BCAT inhibitors and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, neuropathic pain, Parkinson's disease, diabetic retinopathy, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition.
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