- Design, Synthesis and Anticancer Evaluation of New Substituted Thiophene-Quinoline Derivatives
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A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data analysis and evaluated for their anticancer activity. All the derivatives were subjected to in vitro MTT cytotoxicity screening assay against a panel of four different human cancer cell lines, liver (HepG-2), colon (HCT-116), human cervical cancer (HeLa) and breast (MCF-7). Out of a library of 17 compounds, two compounds have been identified as potent and selective cytotoxic agents against HeLa and MCF-7 cell lines. SAR studies for such hybridized analogues were investigated and phenyl derivatives were proved to be more potent than isoxazole and triazole derivatives. Furthermore, the promising compounds were selected for in vitro inhibition of EGFR-TK and Topo II enzymes. Also, they were subjected to cell cycle arrest analysis and apoptosis assay on MCF-7 cells. Our recent finding highlights these thiophene-quinoline analogues as a promising class of compounds for further studies concerning new anticancer therapies.
- Othman, Dina I.A.,Selim, Khalid B.,El-Sayed, Magda A.-A.,Tantawy, Atif S.,Amen, Yhiya,Shimizu, Kuniyoshi,Okauchi, Tatsuo,Kitamura, Mitsuru
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- Tetrahydroquinoline-isoxazole/isoxazoline hybrid compounds as potential cholinesterases inhibitors: Synthesis, enzyme inhibition assays, and molecular modeling studies
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A series of 44 hybrid compounds that included in their structure tetrahydroquinoline (THQ) and isoxazole/isoxazoline moieties were synthesized through the 1,3-dipolar cycloaddition reaction (1,3-DC) from the corresponding N-allyl/propargyl THQs, previously obtained via cationic Povarov reaction. In vitro cholinergic enzymes inhibition potential of all compounds was tested. Enzyme inhibition assays showed that some hybrids exhibited significant potency to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Especially, the hybrid compound 5n presented the more effective inhibition against AChE (4.24 μM) with an acceptable selectivity index versus BChE (SI: 5.19), while compound 6aa exhibited the greatest inhibition activity on BChE (3.97 μM) and a significant selectivity index against AChE (SI: 0.04). Kinetic studies were carried out for compounds with greater inhibitory activity of cholinesterases. Structure–activity relationships of the molecular hybrids were analyzed, through computational models using a molecular cross-docking algorithm and Molecular Mechanics/Generalized Born Surface Area(MM/GBSA) binding free energy approach, which indicated a good correlation between the experimental inhibition values and the predicted free binding energy.
- Rodríguez Nú?ez, Yeray A.,Gutíerrez, Margarita,Alzate-Morales, Jans,Adasme-Carre?o, Francisco,Güiza, Fausto M.,Bernal, Cristian C.,Romero Bohórquez, Arnold R.
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- Synthesis of isoxazoles via 1,3-dipolar cycloaddition reactions: Pharmacological screening for their antioxidant and antimicrobial activities
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In the present study, we report the synthesis of series of novel substituted isoxazoles via 1,3-dipolar cycloaddition reaction. Nitrile oxides generated by the catalytic dehydrogenation of aldoximes by chloramine-T, were trapped in situ by 4-(furan-2-yl)b
- Lokeshwari, Devirammanahalli Mahadevaswamy,Kumar, Kariyappa Ajay
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- In silico design and synthesis of N-arylalkanyl 2-naphthamides as a new class of non-purine xanthine oxidase inhibitors
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A series of N-arylalkanyl 2-naphthamides (Xa~e), which were predicted from virtual molecular docking on a built xanthine oxidase template as potential inhibitors, were synthesized. Their inhibitory activity against xanthine oxidase was assayed. Among these prepared, compounds Xb (IC50 13.6?μM), Xc (IC50 13.1?μM), and Xd (IC50 12.5?μM) showed comparable inhibitory activity to allopurinol (IC50 22.1?μM). The in vitro assay result correlated well with molecular docking scores, ΔG?=??16.99, ?17.66, and ?17.13 Kcal/mol, respectively. On the potassium oxonate-induced hyperuricemic mice model, oral administration of Xc-Ac (40 mg/ Kg), the per-O-acetylated Xc, could reduce the blood uric acid level by 60% in comparison to the normal control group and is statistically significant (p .01) while compared with the hyperuricemic mice group.
- Ho, Sheau Ling,Lin, Ching-Ting,Lee, Shoei-Sheng
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p. 789 - 801
(2021/01/12)
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- Design, synthesis and biological evaluation of novel indanone containing spiroisoxazoline derivatives with selective COX-2 inhibition as anticancer agents
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Objective: A new family of 3′-(Mono, di or tri-substituted phenyl)-4′-(4-(methylsulfonyl) phenyl) spiroisoxazoline derivatives containing indanone spirobridge was designed, synthesized, and evaluated for their selective COX-2 inhibitory potency and cytotoxicity on different cell lines. Methods: A synthetic reaction based on 1,3-dipolar cycloaddition mechanism was applied for the regiospecific formation of various spiroisoxazolines. The activity of the newly synthesized compounds was determined using in vitro cyclooxygenase inhibition assay. The toxicity of the compounds was evaluated by MTT assay. In addition, induction of apoptosis, and expression levels of Bax, Bcl-2 and caspase-3 mRNA in MCF-7 cells were evaluated following exposure to compound 9f. The docking calculations and molecular dynamics simulation were performed to study the most probable modes of interactions of compound 9f upon binding to COX-2 enzyme. Results: The docking results showed that the synthesized compounds were able to form hydrogen bonds with COX-2 involving methyl sulfonyl, spiroisoxazoline, meta-methoxy and fluoro functional groups. Spiroisoxazoline derivatives containing methoxy group at the C-3′ phenyl ring meta position (9f and 9g) showed superior selectivity with higher potency of inhibiting COX-2 enzyme. Furthermore, compound 9f, which possesses 3,4-dimethoxyphenyl on C-3′ carbon atom of isoxazoline ring, exhibited the highest COX-2 inhibitory activity, and also displayed the most potent cytotoxicity on MCF-7 cells with an IC50 value of 0.03 ± 0.01 μM, comparable with that of doxorubicin (IC50 of 0.062 ± 0.012 μM). The results indicated that compound 9f could promote apoptosis. Also, compared to the control group, the mRNA expression of Bax and caspase-3 significantly increased, while that of Bcl-2 significantly decreased upon exposure to compound 9f which may propose the activation of mitochondrial-associated pathway as the mechanism of observed apoptosis. Conclusion: In vitro biological evaluations accompanied with in silico studies revealed that indanone tricyclic spiroisoxazoline derivatives are good candidates for the development of new anti-inflammatory and anticancer (colorectal and breast) agents.
- Abolhasani, Hoda,Zarghi, Afshin,Komeili Movahhed, Tahereh,Abolhasani, Ahmad,Daraei, Bahram,Dastmalchi, Siavoush
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- HCl-mediated cascade cyclocondensation of oxygenated arylacetic acids with arylaldehydes: one-pot synthesis of 1-arylisoquinolines
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In this paper, a concise, open-vessel synthesis of 1-arylisoquinolines is describedviaHCl-mediated intermolecular cyclocondensation of oxygenated arylacetic acids with arylaldehydes in the presence of NH2OH and alcoholic solvents under mild and one-pot reaction conditions. A plausible mechanism is proposed and discussed herein. In the overall reaction process, only water was generated as the byproduct. Various environmentally friendly reaction conditions are investigated for convenient transformationviathe (4C + 1C + 1N) annulation. This protocol provides a highly effective ring closureviathe formations of one carbon-carbon (C-C) bond, two carbon-nitrogen (C-N) bonds and one carbon-oxygen (C-O) bond.
- Hsueh, Nai-Chen,Chen, Shin-Mei,Lin, Chun-Yi,Chang, Meng-Yang
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p. 1047 - 1059
(2021/02/16)
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- Synthesis and SAR study of simple aryl oximes and nitrofuranyl derivatives with potent activity against Mycobacterium tuberculosis
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Background: Oximes and nitrofuranyl derivatives are particularly important compounds in medicinal chemistry. Thus, many researchers have been reported to possess antibacterial, antiparasitic, insecticidal and fungicidal activities. Methods: In this work, we report the synthesis and the biological activity against Mycobacterium tuberculosis H37RV of a series of fifty aryl oximes, ArCH=N-OH, I, and eight nitrofuranyl compounds, 2-nitrofuranyl-X, II. Results: Among the oximes, I: Ar = 2-OH-4-OH, 42, and I: Ar = 5-nitrofuranyl, 46, possessed the best activity at 3.74 and 32.0 μM, respectively. Also, 46, the nitrofuran compounds, II; X = MeO, 55, and II: X = NHCH2Ph, 58, (14.6 and 12.6 μM, respectively), exhibited excellent biological activities and were non-cytotoxic. Conclusion: The compound 55 showed a selectivity index of 9.85. Further antibacterial tests were performed with compound 55 which was inactive against Enterococcus faecalis, Klebisiella pneumonae, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhymurium and Shigel-la flexneri. This study adds important information to the rational design of new lead anti-TB drugs. Structure-activity Relationship (SAR) is reported.
- Calixto, Stephane Lima,Carvalho, Guilherme da Silva Louren?o,Coimbra, Elaine Soares,Granato, Juliana da Trindade,Louren?o, Maria Cristina da Silva,Wardell, James,da Costa, Cristiane Fran?a,de Souza, Marcus Vinicius Nora
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- Chlorotropylium Promoted Conversions of Oximes to Amides and Nitriles
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Chlorotropylium chloride as a catalyst for the transformations of oximes, ketones, and aldehydes to their corresponding amides and nitriles in excellent yields (up to 99 %) and in short reaction times (mostly 10–15 min). Oximes were electrophilically attacked on the hydroxyl oxygen by chlorotropylium. The produced tropylium oxime ethers were the key intermediates, of which the ketoxime ether led to amide through Beckmann rearrangement, and the aldoxime ether led to nitrile by nitrogen base DBU assisted formal dehydration. This chlorotropylium activation protocol offered general, mild, and efficient avenues bifurcately from oximes to both amides and nitriles by one organocatalyst.
- Xu, Jiaxi,Gao, Yu,Li, Zhenjiang,Liu, Jingjing,Guo, Tianfo,Zhang, Lei,Wang, Haixin,Zhang, Zhihao,Guo, Kai
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p. 311 - 315
(2020/01/25)
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- Facile synthesis and docking studies of 7-hydroxyflavanone isoxazoles and acrylates as potential anti-microbial agents
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The present study is aimed to synthesize the novel 7-hydroxyflavanone derived compounds and to assess their biological activity. Two series of compounds such as 2-phenyl-7-((3-phenylisoxazol-5-yl)methoxy)chroman-4-ones (6a–h) and 4-oxo-2-phenylchroman-7-yl acrylates (8a–k) were synthesized from 7-hydroxyflavanone. All the compounds were subjected to anti-microbial activity and molecular docking studies. The results showed that the compounds 6e, 6g–h, 8h–i and 8k were exhibited most potent anti-microbial activity when compared with the standard drugs. Further, the docking studies revealed that the compounds 6a and 8h have the highest binding affinity score of sterol 14-α demethylase and DNA gyrase B respectively. This is the first report assigning unique synthesis of 7-hydroxyflavanone derivatives and their anti-microbial activity proved with in silico studies. Furthermore, the present study is useful for constructive research to synthesize novel compounds along with their biological activity. [Figure not available: see fulltext.].
- Asha Bhanu,China Raju,Jayavardhana Rao,Narasimha,Kesava Rao
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p. 217 - 228
(2019/11/28)
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- SO2F2-Mediated one-pot cascade process for transformation of aldehydes (RCHO) to cyanamides (RNHCN)
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A simple, mild and practical cascade process for the direct conversion of aldehydes to cyanamides was developed featuring a wide substrate scope and great functional group tolerability. This method allows for transformations of readily available, inexpensive, and abundant aldehydes to highly valuable cyanamides in a pot, atom, and step-economical manner with a green nitrogen source. This protocol will serve as a robust tool for the installation of the cyanamide moiety in various complicated molecules.
- Ding, Chengrong,Ge, Shuting,Wei, Junjie,Zhang, Guofu,Zhao, Yiyong
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p. 17288 - 17292
(2020/05/18)
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- Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G
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Using bioisosterism as a medicinal chemistry tool, 16 3,5-diaryl-isoxazole analogues of the tetrahydrofuran neolignans veraguensin, grandisin and machilin G were synthesized via 1,3-dipolar cycloaddition reactions, with yields from 43% to 90%. Antitrypanosomatid activities were evaluated against Trypanosoma cruzi, Leishmania (L.) amazonensis and Leishmania (V.) braziliensis. All compounds were selective for the Leishmania genus and inactive against T.?cruzi. Isoxazole analogues showed a standard activity on both promastigotes of L.?amazonensis and L.?braziliensis. The most active compounds were 15, 16 and 19 with IC50 values of 2.0, 3.3 and 9.5?μM against L.?amazonensis and IC50 values of 1.2, 2.1 and 6.4?μM on L.?braziliensis, respectively. All compounds were noncytotoxic, showing lower cytotoxicity (>250?μM) than pentamidine (78.9?μM). Regarding the structure–activity relationship (SAR), the methylenedioxy group was essential to antileishmanial activity against promastigotes. Replacement of the tetrahydrofuran nucleus by an isoxazole core improved the antileishmanial activity.
- Trefzger, Ozildéia S.,das Neves, Amarith R.,Barbosa, Natália V.,Carvalho, Diego B.,Pereira, Indiara C.,Perdomo, Renata T.,Matos, Maria F. C.,Yoshida, Nidia C.,Kato, Massuo J.,de Albuquerque, Sérgio,Arruda, Carla C. P.,Baroni, Adriano C. M.
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p. 313 - 324
(2018/11/30)
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- Potassium iodate (KIO 3) as a novel reagent for the synthesis of isoxazolines: evaluation of antimicrobial activity of the products
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Abstract : A novel reagent for the synthesis of isoxazolines has been reported. Aryl aldoximes were made to react with alkenes in the presence of KIO 3 as the oxidising agent. This new reagent has been useful as an oxidant in the synthesis of i
- Kotian, Sumana Y,Abishad,Byrappa,Rai, K M Lokanatha
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- Design, docking and synthesis of novel bromo isatin incorporated isoxazole derivatives as vegfr-2 inhibitors
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Objective: To design, synthesize, in vitro Vascular Endothelial Growth Factor Receptor (VEGFR-2) assay, antiproliferative activity an Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) studies of some novel bromoisatin incorporated isoxa
- Radhika,Saisree,Harinadha, Babu V.
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- Synthesis and cytotoxic evaluation of undecenoic acid-based oxime esters
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A series of undecenoic acid-based aldoxime esters have been synthesized using various substituted benzaldehydes and undecenoic acid. These oxime esters have been evaluated for their cytotoxic activities against HeLa, B16-F10, SKOV3, MCF7 and CHO-K1 normal cell line using MTT assay. Most of the synthesized compounds exhibit cytotoxicity. Particularly, 2,3-dimethoxy (IC50 value 12.48μM) and 3-methoxy (IC50 value 13.58μM) derivatives exhibit promising activities against SKOV3 cell lines. All the synthesized compounds are non-toxic towards the Chinese hamster ovary (CHO-K1) normal cell line.
- Vijayendar, Venepally,Kaki, Shiva Shanker,Vamshi Krishna,Misra, Sunil,Prasad,Jala, Ram Chandra Reddy
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p. 1015 - 1022
(2019/05/22)
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- Synthesis and reactivity of platinum(II) triphenylphosphino complexes with aromatic aldoximes
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trans-[Pt(μ-Cl)Cl(PPh3)]2 reacted with arylaldoximes in 1,2-dichloroethane to afford [PtCl2(PPh3){N(OH)[dbnd]CHAr}] (Ar = 3,4-dimethoxyphenyl, 1-naphthyl, 9-anthryl) where aldoxime ligands are N-coordinated to p
- Belli Dell' Amico, Daniela,Colalillo, Marialuigia,Labella, Luca,Marchetti, Fabio,Samaritani, Simona
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supporting information
p. 181 - 186
(2017/09/30)
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- Synthesis of aromatic and indole alpha-glucosinolates
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Aromatic and indole glucosinolates are important members of the glucosinolate family of compounds du to their potential medicinal properties. They are known to exert antioxidant and anti-carcinogenic activity either by the natural products themselves, or their metabolic products including indole-3-carbinol and isothiocyanates. Natural glucosinolates are all β-glucosinolates; however, α-glucosinolates are also promising compounds for medicinal applications and hence have to be produced synthetically for any bio-activity studies. Here we report on the successful synthesis of a series of α-glucosinolates: α-neoglucobrassicin, α-4-methoxyglucobrassicin, 2,3-dichlorophenyl-α-glucosinolate for the first time. Testing for anti-inflammatory properties of these synthetic GLs, however, did not yield the expected activity.
- Vo, Quan V.,Rochfort, Simone,Nam, Pham C.,Nguyen, Tuan L.,Nguyen, Trung T.,Mechler, Adam
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- Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators
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Antibiotic resistance among clinically significant bacterial pathogens is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. Utilizing computational docking method and structure-based optimization strategy, we rationally designed and synthesized two series of isoxazol-3-yl- and isoxazol-5-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compounds B14 and B16 that possessed the isoxazol-5-yl group showed strong antibacterial activity against various testing strains, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. aureus. Further molecular biological studies and docking analyses proved that the compound functioned as an effective inhibitor to alter the dynamics of FtsZ self-polymerization via a stimulatory mechanism, which finally terminated the cell division and caused cell death. Taken together, these results could suggest a promising chemotype for development of new FtsZ-targeting bactericidal agent.
- Bi, Fangchao,Song, Di,Zhang, Nan,Liu, Zhiyang,Gu, Xinjie,Hu, Chaoyu,Cai, Xiaokang,Venter, Henrietta,Ma, Shutao
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- Synthesis of new coumarin tethered isoxazolines as potential anticancer agents
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A series of new coumarin tethered isoxazolines (7a-l) were synthesized and evaluated for their cytotoxic potency against human melanoma cancer cell line (UACC 903) as well as fibroblast normal cell line (FF2441). Preliminary results revealed that some of these coumarin tethered isoxazolines 7b, 7c, 7f and 7j exhibited significant antiproliferative effect against human melanoma cancer (UACC 903) with IC50 values of 8.8, 10.5, 9.2 and 4.5 μM respectively. However, compound 7c was non-toxic to normal human cells at the tested concentration. Further, we have chosen compound 7c to check its efficacy in Ehrlich Ascites Carcinoma animal model in-vivo for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature such as regression of tumor volume. The present study indicates the scope of developing into potent anticancer drug in near future.
- Lingaraju, Gejjalagere S.,Balaji, Kyathegowdanadoddi S.,Jayarama, Shankar,Anil, Seegehalli M.,Kiran, Kuppalli R.,Sadashiva, Maralinganadoddi P.
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supporting information
p. 3606 - 3612
(2018/11/06)
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- Synthesis and Antibacterial Evaluation of Benzofuran Based 3,5-Disubstituted Isoxazoles
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A series of novel benzofuran-isoxazole 7a–7j hybrid heterocyclic molecules are synthesized. The structures of compounds 7a–7j are assessed by IR, NMR, MASS spectroscopy and elemental analysis. The target compounds 7a–7j are screened for their antibacterial activity and demonstrated excellent to moderate activity against gram-positive and gram-negative bacteria.
- Sunitha,Kumar, A. Kishore,Lincoln, Ch. Abraham,Jalapathi,Reddy, V. Gopal
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p. 2669 - 2674
(2019/04/04)
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- Synthesis of novel 2H-chromene-3-carboxylate isoxazole/isoxazoline derivatives via 1,3-dipolar cycloaddition reaction (NOAC)
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Synthesis of novel (3-phenylisoxazol-5-yl)methyl-2H-chromene-3-carboxylates (7a–7d) and (3-phenyl-4,5-dihydroisoxazol-5-yl)methyl-2H-chromene-3-carboxylates (8a–8p) by 1,3-dipolar cycloaddition, and nitrile oxide and alkyne cycloaddition (NOAC) is presented. The products are characterised by IR, 1H and 13C NMR, and ESI-MS data.
- Srinivas,Krupadanam
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p. 331 - 339
(2017/04/13)
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- Design and synthesis of neolamellarin a derivatives targeting heat shock protein 90
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In this study, we designed and synthesized a novel family of neolamellarin A derivatives that showed high inhibitory activity toward heat shock protein 90 (Hsp90), a kinase associated with cell proliferation. The 3,4-bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N position of pyrrole are essential to the Hsp90 inhibitory activity and cytotoxicity of these compounds. Western blot analysis demonstrated that these compounds induced dramatic depletion of the examined client proteins of Hsp90, and accelerated cancer cell apoptosis. Docking simulations suggested that the binding mode of 9p was similar to that of the VER49009, a potent inhibitor of Hsp90. Further molecular dynamics simulation indicated that the hydrophobic interactions as well as the hydrogen bonds contributed to the high affinity of 9p to Hsp90.
- Jiang, Long,Yin, Ruijuan,Wang, Xueting,Dai, Jiajia,Li, Jing,Jiang, Tao,Yu, Rilei
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supporting information
p. 24 - 33
(2017/04/21)
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- Compounding method for hellebore amide
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The invention provides a compounding method for hellebore amide. An ultraviolet spectrum technique and a mass-spectrometric technique are used for representing the structure of hellebore amide. The hellebore amide is prepared according to the following steps: performing nucleophilic addition on veratraldehyde and hydroxylamine hydrochloride and then performing beckmann rearrangement under the catalytic effect of cation exchange resin. The compounding method for hellebore amide has the advantages of simple compound process, high yield, reusable catalyst and benefit to realization of industrial production.
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Paragraph 0017
(2017/07/19)
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- 1,3-Dipolar cycloaddition of uracil derivatives with nitrile oxides: Synthesis of [1,2,4]oxadiazolo[4,5-c]pyrimidine-5,7(6H)-dione derivatives
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An efficient method of synthesizing bicyclic fused [1,2,4]oxadiazolo[4,5-c]pyrimidine-5,7(6H)-dione derivatives was developed through a [3 + 2] cycloaddition of uracil derivatives and nitrile oxides. In the one step reaction, C[sbnd]N and C[sbnd]O bonds were constructed, the target compounds were efficiently obtained in good yields. The method represents a valuable way to obtain highly functional fused bicyclic heterocycle derivatives in a simple, rapid and practical manner. The method fusing bicyclic heterocycles can be applied for modification of uracil analogues that may have potential biological activities.
- Jiang, Kun-Ming,Jin, Yi,Lin, Jun
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p. 6662 - 6668
(2017/10/23)
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- An efficient one-pot protocol for the conversion of benzaldehydes into tetrazole analogs
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An efficient protocol has been developed for the one-pot synthesis of tetrazole derivatives in moderate to good yields starting from substituted benzaldehydes and proceeding via non-isolated oxime and nitrile intermediates. The structures of the desired products were confirmed by IR, and NMR spectroscopy as well as mass spectrometry. A plausible reaction mechanism is also discussed.
- Khan, Khalid Mohammed,Fatima, Itrat,Saad, Syed Muhammad,Taha, Muhammad,Voelter, Wolfgang
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p. 523 - 524
(2016/01/20)
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- Design, synthesis, molecular docking studies and anti-HBV activity of phenylpropanoid derivatives
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In this work, a series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated. Most of the synthesized derivatives showed effective anti-HBV activity. And compound 4d-3 showed the most effective anti-HBV activity, performing strong potent inhibitory not only on the secretion of HBsAg (IC50 = 58.28 μM, SI = 23.26) and HBeAg (IC50 = 97.21 μM, SI = 13.95), but also on the HBV DNA replication (IC50 = 42.28 μM, SI = 32.06). The structure-activity relationships (SARs) of the derivatives had been discussed, which were useful for developing phenylpropanoid derivatives as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site was carried out to explore the molecular interactions and a molecular target for activity and a modified assay method measuring the interaction between our derivatives and HBcAg was investigated, indicating that the HBV core protein might be their potential target for anti-HBV. This study identified a new class of potent non-nucleoside anti-HBV agents.
- Liu, Sheng,Li, Yubin,Wei, Wanxing,Wang, Kuiwu,Wang, Lisheng,Wang, Jianyi
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- (Thiolan-2-yl)diphenylmethyl benzyl ether/N,N′-diarylurea cocatalyzed asymmetric aziridination of cinnamyl bromide and aryl aldimine
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A dual catalyst system using THT-based chiral sulfide 2a and H-bond donor 10a was developed for the asymmetric imino Corey-Chaykovsky reaction. Under the optimum reaction conditions, cinnamyl bromide reacted with a wide scope of N-diphenylphosphinic aldim
- Wang, Shang-Hua,Chein, Rong-Jie
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supporting information
p. 2607 - 2615
(2016/05/11)
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- Highly efficient and stable peracid for rapid and selective oxidation of aliphatic amines to oximes
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A novel, transition-metal free, rapid approach for selective oxidation of aliphatic and benzylic amines to oximes is described. The dodecanebis(peroxoic acid)-DMF combination efficiently oxidizes various aliphatic amines at 50 °C temperature to give 100% conversion in 20 min with high oxime selectivity. The peroxy acid used here shows exceptional stability at room temperature and is non-shock sensitive in nature, which was confirmed by differential scanning colorimetric (DSC) analysis.
- Patil, Vilas V.,Gayakwad, Eknath M.,Shankarling, Ganapati S.
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p. 6677 - 6682
(2015/08/06)
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- Synthesis and biological evaluation of novel Δ2-isoxazoline fused cyclopentane derivatives as potential antimicrobial and anticancer agents
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As a part of our endeavour toward the synthesis of new heterocyclic bioactive agents, three series of Δ2-isoxazoline fused cyclopentane derivatives (27 compounds) were synthesized and characterized by IR, 1H NMR, 13C NMR and MS analysis. The newly synthesized target compounds were evaluated for their preliminary in vitro antimicrobial and anticancer activities. The results indicated that compounds 4b, 4h, 4i, 5d and 5g displayed remarkable anti-microbial activity with respect to their standard drugs Ampicillin, Gentamycin and Amphotericin B. In preliminary MTT cytotoxicity studies, compound 4i was found to be equipotent to the standard drug Etoposide against MCF-7. The influence of the most active cytotoxic compound 4i on the cell cycle distribution was evaluated in the MCF-7 cell line, which displayed a cell cycle arrest at the S phase. Moreover, acridine orange/ethidium bromide staining, annexin V binding assay and mitochondrial membrane potential revealed that compound 4i can induce cell apoptosis in MCF-7 cells. Compounds 4b and 4h are potential leads as antimicrobials owing to no significant cell toxicity observed in the present study. Docking studies revealed that compound 4i binds to Phe1145, Glh698, Met696, Cys1191, Met1169 and Ile1167 on DNA methyltransferase (DNMT1) protein and inhibition of DNMT1 could be the possible mechanism of action for these compounds.
- Prajapti, Santosh Kumar,Shrivastava, Shweta,Bihade, Umesh,Gupta, Ajay Kumar,Naidu,Banerjee, Uttam Chand,Babu, Bathini Nagendra
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supporting information
p. 839 - 845
(2015/05/27)
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- APPLICATIONS OF N6-SUBSTITUTED ADENOSINE DERIVATIVE AND N6-SUBSTITUTED ADENINE DERIVATIVE TO CALMING, HYPNOSES, CONVULSION RESISTANCE, EPILEPTIC RESISTANCE, PARKINSON DISEASE RESISTANCE, AND DEMENTIA PREVENTION AND TREATMENT
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PROBLEM TO BE SOLVED: To prepare analgesics, hypnotic agents, anticonvulsant agents, antiepileptics, antiparkinson drugs, dementia prophylactics, and health care food. SOLUTION: The present invention relates to an N6-substituted adenosine derivative and an N6-substituted adenine derivative selected from the group consisting of specific compounds. The present invention also relates to a pharmaceutical composition at least comprising a therapeutically effective amount of the compounds and a pharmaceutically acceptable carrier. The invention further relates to the compounds used in preparation of analgesics, hypnotic agents, anticonvulsant agents, antiepileptics, antiparkinson drugs, dementia prophylactics, and health care food. COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0122
(2018/10/27)
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- Synergistic effect of dual-frequency ultrasound irradiation in the one-pot synthesis of 3,5-disubstituted isoxazoles
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Herein is reported a one-pot three-step process for the regioselective synthesis of 3,5-disubstituted isoxazoles based on copper(I)-catalyzed cycloaddition reaction between in situ generated nitrile oxides (from the corresponding aldehydes) and alkynes, u
- Koufaki, Maria,Fotopoulou, Theano,Heropoulos, Georgios A.
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- Enantioselective synthesis of diaryl aziridines using tetrahydrothiophene- based chiral sulfides as organocatalysts
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This work describes catalytic and asymmetric aziridinations (15 examples, 95-98% ee) of benzyl bromide and imines via the imino Corey-Chaykovsky reaction using (thiolan-2-yl)diarylmethanol benzyl ether as an organocatalyst. The catalyst and analogues thereof were prepared through an expeditious and efficient synthetic route featuring a double nucleophilic substitution and Shi epoxidation as key steps.
- Huang, Meng-Ting,Wu, Hsin-Yi,Chein, Rong-Jie
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supporting information
p. 1101 - 1103
(2014/01/17)
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- Sodium nitrite-catalyzed aerobic oxidative Csp2-Csp3 coupling: Direct construction of the 4-aryldihydroisoquinolinone moiety
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A bioinspired approach for the construction of the 4- aryldihydroisoquinolinone moiety via direct oxidative Csp2-Csp 3 coupling has been developed, which uses inexpensive sodium nitrite as catalyst and environmentally benign oxygen in the air as terminal oxidant.
- Su, Bo,Deng, Meng,Wang, Qingmin
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supporting information
p. 977 - 981
(2014/04/03)
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- Microwave-assisted synthesis of 3,5-disubstituted isoxazoles and evaluation of their anti-ageing activity
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One-pot uncatalysed microwave-assisted 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxides and alkynes bearing protected antioxidant substituents, were regioselectively afforded 3,5-disubstituted isoxazoles. The yields were modera
- Koufaki, Maria,Fotopoulou, Theano,Kapetanou, Marianna,Heropoulos, Georgios A.,Gonos, Efstathios S.,Chondrogianni, Niki
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p. 508 - 515
(2014/07/21)
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- Organocatalytic, diastereo- and enantioselective synthesis of nonsymmetric cis -stilbene diamines: A platform for the preparation of single-enantiomer cis -imidazolines for protein-protein inhibition
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The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein-protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small molecules (i.e., Nutlin-3) provided only the racemic form, with enantiomers being enriched by chromatographic separation using high-pressure liquid chromatography (HPLC) and a chiral stationary phase. Reported here is the first application of an enantioselective aza-Henry approach to nonsymmetric cis-stilbene diamines and cis-imidazolines. Two novel mono(amidine) organocatalysts (MAM) were discovered to provide high levels of enantioselection (>95% ee) across a broad range of substrate combinations. Furthermore, the versatility of the aza-Henry strategy for preparing nonsymmetric cis-imidazolines is illustrated by a comparison of the roles of aryl nitromethane and aryl aldimine in the key step, which revealed unique substrate electronic effects providing direction for aza-Henry substrate-catalyst matching. This method was used to prepare highly substituted cis-4,5-diaryl imidazolines that project unique aromatic rings, and these were evaluated for MDM2-p53 inhibition in a fluorescence polarization assay. The diversification of access to cis-stilbene diamine-derived imidazolines provided by this platform should streamline their further development as chemical tools for disrupting protein-protein interactions.
- Vara, Brandon A.,Mayasundari, Anand,Tellis, John C.,Danneman, Michael W.,Arredondo, Vanessa,Davis, Tyler A.,Min, Jaeki,Finch, Kristin,Guy, R. Kiplin,Johnston, Jeffrey N.
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p. 6913 - 6938
(2014/08/18)
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- Synthesis and anti-inflammatory activity of aromatic glucosinolates
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Aromatic GLs are important members of the glucosinolate family of compounds because of their potential biological activity and medicinal properties. This study has shown success in the high yielding synthesis of some important aromatic GLs as well as the results of testing for anti-inflammatory properties of the synthetic GLs. 3,4-Dimethoxyphenylglucosinolate was found to be the most active anti-inflammatory of the seven glucosinolates assayed.
- Vo, Quan V.,Trenerry, Craige,Rochfort, Simone,Wadeson, Jenny,Leyton, Carolina,Hughes, Andrew B.
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p. 5945 - 5954
(2013/09/23)
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- Synthesis and evaluation of 4,5-dihydro-5-methylisoxazolin-5-carboxamide derivatives as VLA-4 antagonists
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A novel set of compounds containing a 4,5-dihydro-5-methylisoxazoline have been successfully designed as VLA-4 receptor antagonists. Compound (14p) had a high receptor binding affinity of 4 nM and also found to be metabolically stable in vitro.
- Soni, Ajay,Rehman, Abdul,Naik, Keshav,Dastidar, Sunanda,Alam,Ray, Abhijit,Chaira, Tridib,Shah, Vanya,Palle, Venkata P.,Cliffe, Ian A.,Sattigeri, Viswajanani J.
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p. 1482 - 1485
(2013/03/14)
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- One-pot synthesis of dihydrobenzisoxazoles from hydroxylamines, acetylenedicarboxylates, and arynes via in situ generation of nitrones
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Aryne [3 + 2] cycloaddition with nitrones generated in situ from the addition of hydroxylamines to acetylenedicarboxylates affords moderate to good yields of dihydrobenzisoxazoles. This reaction extends the current scope of aryne cycloaddition to include in situ generated nitrones and produces functionalized dihydrobenzisoxazoles with a quaternary center.
- Li, Pan,Wu, Chunrui,Zhao, Jingjing,Li, Yang,Xue, Weichao,Shi, Feng
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supporting information
p. 43 - 50
(2013/03/14)
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- N6-SUBSTITUTED ADENOSINE DERIVATIVES AND N6-SUBSTITUTED ADENINE DERIVATIVES AND USES THEREOF
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The present invention provides N6-substituted adenosine derivatives and N6-substituted adenine derivatives, manufacturing methods thereof, a pharmaceutical composition comprising the said compounds above, and uses of these compounds in manufacturing medicaments and health-care products for treating insomnia, convulsion, epilepsy, and Parkinson's diseases, and preventing and treating dementia.
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Paragraph 0184
(2013/03/26)
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- Synthesis of podophyllotoxin and its derivatives via nicl2/nabh4 reduction of isoxazoline ring
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A novel synthesis of podophyllotoxin was carried out in four steps. The key step was reduction of isoxazoline ring followed by diazotization and the resultant alkene was treated with Mn(OAc)3/CH3COOK to form podophyllotoxin.
- Babu, Meduri Suresh,Rai, Kuria Madhavu Lokanatha
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p. 9555 - 9557
(2014/01/06)
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- Synthesis, characterization and biological evaluation of some novel 17-isoxazoles in the estrone series
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Regioselective 1,3-dipolar cycloadditions of different aryl nitrile oxides to mestranol were carried out to furnish novel steroidal 17α-isoxazoles in good to excellent yields. Copper(I) was found to be an efficient catalyst, accelerating the intermolecula
- Kovacs, Dora,Kadar, Zalan,Motyan, Gerg,Schneider, Gyula,Woelfling, Janos,Zupko, Istvan,Frank, Eva
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p. 1075 - 1085
(2012/11/07)
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- N6-SUBSTITUTED ADENOSINE DERIVATIVES, N6-SUBSTITUTED ADENINE DERIVATIVES AND USES THEREOF
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The present invention provides N6-substituted adenosine derivatives and N6-substituted adenine derivatives, manufacturing methods thereof, a pharmaceutical composition comprising the said compounds above, and uses of of these compounds in manufacturing medicaments and health-care products for treating insomnia, convulsion, epilepsy, and Parkinson's diseases, and preventing and treating dementia.
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Page/Page column 54
(2012/11/06)
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- Discovery, synthesis, and biological evaluation of a novel group of selective inhibitors of filoviral entry
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Herein, we report the development of an antifiloviral screening system, based on a pseudotyping strategy, and its application in the discovery of a novel group of small molecules that selectively inhibit the Ebola and Marburg glycoprotein (GP)-mediated infection of human cells. Using Ebola Zaire GP-pseudotyped HIV particles bearing a luciferase reporter gene and 293T cells, a library of 237 small molecules was screened for inhibition of GP-mediated viral entry. From this assay, lead compound 8a was identified as a selective inhibitor of filoviral entry with an IC50 of 30 μM. To analyze functional group requirements for efficacy, a structure-activity relationship analysis of this 3,5-disubstituted isoxazole was then conducted with 56 isoxazole and triazole derivatives prepared using "click" chemistry. This study revealed that while the isoxazole ring can be replaced by a triazole system, the 5-(diethylamino)acetamido substituent found in 8a is required for inhibition of viral-cell entry. Variation of the 3-aryl substituent provided a number of more potent antiviral agents with IC50 values ranging to 2.5 μM. Lead compound 8a and three of its derivatives were also found to block the Marburg glycoprotein (GP)-mediated infection of human cells.
- Yermolina, Maria V.,Wang, Jizhen,Caffrey, Michael,Rong, Lijun L.,Wardrop, Duncan J.
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experimental part
p. 765 - 781
(2011/04/15)
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- Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent
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Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton. Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active inhibitor, 4-((3-(4-hydroxy-3- methoxyphenyl)-4, 5-dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b) was evaluated against huMIF-induced inflammation in a cellular model (RAW 264.7 cell). Compound 4b significantly inhibits huMIF-mediated NF-κB translocation to the nucleus, up-regulation of inducible nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation. The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has potential to be a novel anti-inflammatory agent.
- Alam, Athar,Pal, Chinmay,Goyal, Manish,Kundu, Milan Kumar,Kumar, Rahul,Iqbal, Mohd Shameel,Dey, Sumanta,Bindu, Samik,Sarkar, Souvik,Pal, Uttam,Maiti, Nakul C.,Adhikari, Susanta,Bandyopadhyay, Uday
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experimental part
p. 7365 - 7373
(2012/01/06)
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- A rapid and convenient method for the synthesis of aldoximes under microwave irradiation using in situ generated ionic liquids
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We have developed a chemoselective, simple and efficient method for the preparation of aldoximes using microwave irradiation in the presence of tribenzylamine or 1,4-diazabicyclo[2.2.2]octane or 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide as bases and useful precursors for in situ generation of ionic liquids.
- Hajipour,Rafiee,Ruoho
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experimental part
p. 114 - 118
(2010/10/21)
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- Preparative synthesis of veratraldehydeoxime esters
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Preparative syntheses of veratraldehydeoxime esters 6-24, available fragrances produced from vanillin (1), in 82-92% yield from veratraldehydeoxime (3) were developed.
- Zhukovskaya,Dikusar,Vyglazov
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experimental part
p. 688 - 691
(2009/04/10)
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- A simple and effective glycine-catalysed procedure for the preparation of oximes
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Ketoximes and aldoximes are expeditiously prepared by the reaction of the corresponding carbonyl compound with hydroxylamine hydrochloride in dimethylformamide, in the presence of a sub-stoichiometric quantity of glycine at room temperature. Mild (non-hydroxylic) conditions, simple workup and high yield characterise the methodology.
- Maheswara, Muchchintala,Siddaiah, Vidavalur,Gopalaiah, Kovuru,Rao, Vallabhaneni Madhava,Rao, Chunduri Venkata
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p. 362 - 363
(2007/10/03)
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- One-pot synthesis and hydroxylaminolysis of asymmetrical acyclic nitrones
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Aromatic aldehydes 1 were reductively aminated to the corresponding secondary amines 2 using NaBH4 in methanol in good yields. Amines 2 were oxidized with H2O2-WO42- regioselectively to nitrones 3, the structures of which were easily determined by reacting them with hydroxylamine hydrochloride as well as by spectral means. The products of hydroxylaminolysis in ether proved to be the corresponding benzaldehyde oximes 4 and benzyl or methyl hydroxylamine hydrochlorides 5. Copyright Taylor & Francis, Inc.
- Coskun, Necdet,Parlar, Aydin
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p. 2445 - 2451
(2007/10/03)
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- Catalytic effect of wet molecular sieve 3A in dry media on syntheses of oximes and 1,3-dioximes
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A simple, efficient and eco-friendly method has been developed for the condensation of hydroxylamine hydrochloride with aldehydes, ketones and 1,3-diketones in the presence of powdered molecular sieves (3A) as catalyst. Aldoximes, ketoximes and 1,3-dioximes were obtained in excellent yields.
- Bigdeli, Mohammadali,Rahmati, Abbas
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p. 605 - 607
(2007/10/03)
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- Reduction of aldehydes and oximes to their corresponding alcohols and amines by catalytic hydrogenation method
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The reduction of aldehydes such as 2-butyl-5-chloro-3H-imidazole-5- carbaldehyde and veratraldehyde, which are pharmaceutical key intermediates, have been reduced to alcohols by catalytic hydrogenation method in the presence of magnesium and also oximes are reduced to primary amines successively by magnesium/ammonium formate system, is a large scale feasible and cheaper method. The crystal structure of the product, (2-butyl-5-chloro-3H-imidazole-4-yl)- methanol 1 is reported.
- Basappa,Doreswamy,Mahendra,Mantelingu,Sridhar,Prasad, J. Shashidhara,Rangappa
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p. 148 - 151
(2007/10/03)
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- An efficient method for the preparation of nitriles via the dehydration of aldoximes with phthalic anhydride
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A new and highly efficient method for the conversion of aldoximes to nitriles was established. By fusing with phthalic anhydride, aldoximes were efficiently and smoothly converted into nitriles, in high yields (over 85%) and in a short time (within 5 minutes). The mixture of phthalic anhydride, a cyclic anhydride, and aldoximes in fusing state set up an ideal transition state for a selective [3.3]-sigmatropic rearrangement of the acylated aldoximes to nitriles.
- Wang, Eng-Chi,Huang, Keng-Shiang,Chen, Hsing-Ming,Wu, Chung-Chin,Lin, Gwo-Jiun
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p. 619 - 627
(2007/10/03)
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