- Efficient synthesis of 1,2,4-oxadiazine-5-ones via [3+3] cycloaddition of in situ generated aza-oxyallylic cations with nitrile oxides
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1,2,4-Oxadiazin-5-ones were prepared via [3+3] cycloaddition of in situ generated aza-oxyallylic cations with nitrile oxides in good yields and excellent functional group compatibility. This efficient transformation is metal-free and is promoted by an inorganic base Cs2CO3. In addition, this reaction features simple-operation, mild conditions, and high regioselectivity.
- Wang, Gangqiang,Chen, Rongxing,Zhao, Sen,Yang, Liangfeng,Guo, Haibing,Sun, Shaofa,Wang, Jian,Domena, Justin,Xing, Yalan
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- Synthesis and evaluation of spiroisoxazoline oxindoles as anticancer agents
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Restoring p53 levels through disruption of p53-MDM2 interaction has been proved to be a valuable approach in fighting cancer. We herein report the synthesis and evaluation of eighteen spiroisoxazoline oxindoles derivatives as p53-MDM2 interaction inhibito
- Ribeiro, Carlos J.A.,Amaral, Joana D.,Rodrigues, Cecília M.P.,Moreira, Rui,Santos, Maria M.M.
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- Highly regioselective 1,3-dipolar cycloaddition of 3′-O-propargyl guanosine with nitrile oxide: An efficient method for the synthesis of guanosine containing isoxazole moiety
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The 1,3-dipolar cycloaddition reaction of 3′-O-propargyl guanosine with various in-situ generated nitrile oxides in the presence of DMF as a solvent is described. It is noteworthy that the reaction is highly regioselective that affords biologically import
- Kore, Anilkumar R.,Senthilvelan, Annamalai,Shanmugasundaram, Muthian
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- Synthesis and biological evaluation of novel isoxazole derivatives from acridone
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The present study was carried out in an?attempt to synthesize a new class of potential antibacterial agents. In this context, novel isoxazoles were synthesized and evaluated for their potential antibacterial behavior against four pathogenic bacterial strains. The synthesized compounds exhibited moderate-to-good antibacterial activity against these strains. The highest antibacterial activity was observed against the Escherichia coli strains, particularly for compounds 4a and 4e with phenyl and para-nitrophenyl groups on the isoxazole–acridone skeleton;?they showed promising minimum inhibitory concentration values of 16.88 and 19.01 μg/ml, respectively, compared with the standard drug chloramphenicol (22.41 μg/ml). The synthesized compounds were subjected to in silico docking studies to understand the mode of their interactions with the DNA topoisomerase complex (PDB ID: 3FV5) of E. coli. The molecular docking results showed that compounds 4a–l occupy the active site of DNA topoisomerase (PDB ID: 3FV5), stabilized via hydrogen bonding and hydrophobic interactions, which may be the reason behind their interesting in vitro antibacterial activity.
- Aarjane, Mohammed,Slassi, Siham,Tazi, Bouchra,Amine, Amina
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- Efficient synthesis of bis-isoxazole ethers via 1,3-dipolar cycloaddition catalysed by Zn/Zn2+ and their antifungal activities
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An efficient method was developed for synthesising isoxazoles. A series of novel bis-isoxazole ether compounds VI, VII and VIII were synthesised starting from different substituted aldehydes (I) via a 1,3-dispolar cycloaddition using Zn/Zn2+ as a catalyst; these were characterised by FT-IR, HRMS, 1H NMR and 13C NMR spectroscopy. In addition, the antimicrobial properties of the synthesised products were investigated. The synthesised compounds exhibited significant antifungal activities in comparison with the standard drugs, fluconazole and itraconazole. It was found that Candida albicans was sensitive to 2-substituted phenyl bis-isoxazole ethers bearing pyridyl.
- Zhang, Da-Wei,Lin, Feng,Li, Bo-Chao,Liu, Hong-Wei,Zhao, Tian-Qi,Zhang, Yu-Min,Gu, Qiang
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- A novel cleavage for polystyrene-supported selenium resins: An efficient route to 3,5-disubstituted isoxazolines and their derivatives
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We report here a novel cleavage method for polystyrene-supported selenium resin using CH3I-NaI under mild conditions to prepare 3,5-disubstituted isoxazolines. The polymer selenium resins can be reused without further transformation. Georg Thie
- Xu, Wei-Ming,Wang, Yu-Guang,Miao, Mao-Zhong,Huang, Xian
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- Synthesis and chemical modification of 3,3-dimethyl-1H,3H-furo[4,3- b][1,5]benzothiazepin-1-one
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Heating of 3-(2-aminophenylthio)-2-methoxycarbonyl-4-methyl-2-penten-4- olide with triethylamine hydrochloride gave 3,3-dimethyl-1H,3H-furo[4,3- b][1,5]benzothiazepin-1-one. Some chemical modifications of the product including [2 + 2]cycloaddition and 1,3-dipolar cycloaddition to the imino group in the product were performed.
- Matsuo,Sunago,Okutani,Takagi,Nakamoto,Kobayashi
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- Synthesis of novel isoxazoline-containing podophyllotoxin/2′(2′,6′)-(di)halogenopodophyllotoxin derivatives and their insecticidal/acaricidal activities
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In continuation of our program aimed at the development of natural product-based pesticidal agents, a series of isoxazoline-containing podophyllotoxin/2′(2′,6′)-(di)halogenopodophyllotoxin derivatives were prepared, and their structures were well characte
- Yang, Ruige,Zhang, Yuanyuan,Xu, Hui
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- Synthesis and evaluation of novel isoxazolyl chalcones as potential anticancer agents
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A series of novel isoxazolyl chalcones were synthesized and evaluated for their activities in vitro against four types of human non-small cell lung cancer cells, including H1792, H157, A549 and Calu-1 cells. The preliminary biological screening showed tha
- Wan, Maosheng,Xu, Linyan,Hua, Li,Li, Ailing,Li, Shuqing,Lu, Wenjing,Pang, Yue,Cao, Chengbo,Liu, Xiangguo,Jiao, Peifu
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- Substituent effect study on experimental 13C NMR chemical shifts of (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene)diacetate derivatives
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Abstract Eleven novel (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene) diacetate derivatives were synthesized in the present study. These dihydroisoxazole derivatives were characterized by IR, 1H NMR, 13C NMR
- Kara, Yesim S.
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- Cu(I) catalyzed microwave assisted telescopic synthesis of 3,5-disubstituted isoxazoles in green media
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A facile and efficient microwave assisted telescopic synthesis of diverse isoxazoles was reported in green reaction medium. Initially, N-hydroxyl imidoyl chlorides were reacted with substituted alkynes in aqueous medium using 2 mol% of [Cu(phen)(PPh3
- Meena,Maiti, Barnali,Chanda, Kaushik
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- Addition of nitrile oxides to allyl esters of aryl-(hetaryl)carboxylic acids
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3,5-Disubstituted isoxazolines with an aryl(hetaryl) carboxymethyl group in position 5 have been synthesized. The addition reaction of nitrile oxides to allyl esters of aryl(hetaryl) carboxylic acids occurs regiospecifically with the formation of the 5-su
- Dirnens,Slyadevskaya,Lukevics
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- Safe and scaleable oxidation of benzaldoximes to benzohydroximinoyl chlorides
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Benzohydroximinoyl chlorides are useful precursors to nitrile oxides used in the preparation of various heterocycles via 1,3-dipolar cycloadditions. These intermediates are typically accessed by oxidation of aldoximes using N-chlorosuccinimide. This simpl
- Hansen, Eric C.,Levent, Mahmut,Connolly, Terrence J.
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- 1,3-Dipolar Cycloaddition, HPLC Enantioseparation, and Docking Studies of Saccharin/Isoxazole and Saccharin/Isoxazoline Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors
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Two series of saccharin/isoxazole and saccharin/isoxazoline hybrids were synthesized by 1,3-dipolar cycloaddition. The new compounds showed to be endowed with potent and selective inhibitory activity against the cancer-related human carbonic anhydrase (hCA) IX and XII isoforms in the nanomolar range, while no affinity was encountered for off-targets, such as hCA I and II. Successive enantioseparation on a milligram scale of the most representative compounds led to the discovery that (S)-isomers were more potent than their corresponding (R)-enantiomers. Lastly, molecular modeling studies were conducted to define those structural requirements that were responsible for the discrimination among selected human isoforms of carbonic anhydrases. Two nanomolar hCA IX and XII inhibitors were also screened for their selective toxicity against non tumoral primary cells (fibroblasts) and against a breast adenocarcinoma cell line (MCF7) in hypoxic environment. The efficacious combination of these compounds with doxorubicin on MCF7 cells was demonstrated after 72 h of treatment.
- D'Ascenzio, Melissa,Secci, Daniela,Carradori, Simone,Zara, Susi,Guglielmi, Paolo,Cirilli, Roberto,Pierini, Marco,Poli, Giulio,Tuccinardi, Tiziano,Angeli, Andrea,Supuran, Claudiu T.
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- Reaction of nitrile oxides with vinylphosphonate: A facile, regioselective approach to 5-phosphonyl-4, 5-dihydroisoxazoles
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The synthesis of 5-phosphonyl-4,5-dihydroisoxazoles from nitrile oxides and diethylvinylphosphonate was discussed. The structure of these compounds were determined by 1H NMR spectroscopy. It was found that the phosphonyl group of dipolarophiles
- Ye, Yong,Zheng, Yu,Xu, Guo-Yan,Liu, Lun-Zu
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- An efficient protocol for the synthesis of six-membered N, O-heterocycles via a 1,3-dipolar (3+3) cycloaddition between nitrile oxide and α-diazo esters
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In this manuscript, we are reporting an efficient protocol for the construction of highly functionalized N, O-heterocyclic derivatives such as 1,2,4-oxadiazine and 1,4,2-dioxazine-6-carboxylate derivatives via a 1,3-dipolar (3 + 3) cycloaddition between nitrile oxide and unprotected α-diazo esters in the presence of 2 mol% Cu(OTf)2 catalyst. The expected N, O-heterocycles were obtained in excellent yields. These N, O-heterocycles are known to exhibit insecticidal and acaricidal properties.
- Kuruba, Bharath Kumar,Vasanthkumar, Samuel
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- Reactions of Nitrile Oxides and Nitrilimines with Imidate Esters, the Nitrogen Atom of which forms Part of a Heterocyclic Ring
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The cycloaddition reactions of three cyclic imidate esters, 2-ethoxypyrrolin-5-one (6), 2-ethoxyisoindol-3-one (7) and 2-ethoxy-1H-indol-3-one (8) with various 1,3-dipoles were investigated.Dipolarophile 6 added only to nitrile oxides; 8 added to nitrile
- Miller, David J.,Scrowston, Richard M.,Kennewell, Peter D.,Westwood, Robert
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- Design, synthesis, in vitro and in silico evaluation of new 3-phenyl-4,5-dihydroisoxazole-5-carboxamides active against drug-resistant mycobacterium tuberculosis
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A new series of 3-phenyl-4,5-dihydroisoxazole-5-carboxamides were designed, synthesized, and evaluated for their potency against Mtb H37Rv. Designed molecules were synthesized by one-pot cycloaddition reaction in good to excellent yields. Anti-Tubercular evaluation of all synthesized derivatives identified 6k to be highly potent (MIC 1 μg/mL) against Mtb and drug-resistant strains. All potent derivatives were found to be non-toxic when tested against Vero cells. Also, in silico studies were employed to explore the binding patterns of designed compounds to target Mycobacterial membrane protein Large-3. All derivatives exhibited excellent binding patterns with the receptor. The excellent in silico Absorption, Distribution, Metabolism, and Excretion properties and druggability parameters positions these molecules as promising lead candidates for the future development of new drugs to treat drug-resistant Tuberculosis.
- Gaikwad, Nikhil Baliram,Afroz, Pathan,Ahmad, Mohammad Naiyaz,Kaul, Grace,Shukla, Manjulika,Nanduri, Srinivas,Dasgupta, Arunava,Chopra, Sidharth,Yaddanapudi, Venkata Madhavi
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- Design and synthesis of sinomenine isoxazole derivatives via 1,3-dipolar cycloaddition reaction
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A novel structure of sinomenine isoxazole derivatives is synthesised from sinomenine hydrochloride and aromatic aldehydes and requires six steps. 19 target compounds have been obtained in good yields. The sinomenine hydrochloride transforms to 4-alkynyl sinomenine, which is a key intermediate product to synthesise the target sinomenine isoxazole compounds, after a neutralisation reaction with ammonia and substitution reaction with 3-chloropropyne. Another key intermediate product is 1,3-dipole, which can be obtained from aromatic aldehyde. After treatment with hydroxylamine hydrochloride and then sodium carbonate solution, aromatic aldehyde is converted to aldehyde oxime, which reacts with N-chlorosuccinimide (NCS) to afford aryl hydroximino chloride. 1,3-Dipole is eventually formed in situ while triethylamine (TEA) in DMF is added dropwise. Then 4-alkynyl sinomenine is added to provide the sinomenine isoxazole derivative via 1,3-dipolar cycloaddition reaction as the key step. All the target compounds are characterised by melting point, 1H NMR, 13C NMR, HRMS and FT-IR spectroscopy.
- Pan, Hongmei,Lu, Tong,Wu, Xuedan,Gu, Chengwen,Tao, Naili,Zhang, Biao,Wang, Ao,Chen, Guangmei,Zhang, Kehua,Cheng, Jie,Jin, Jie
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supporting information
p. 2360 - 2364
(2019/11/11)
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- Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
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α-Glucosidase inhibition is a valid approach for controlling hyperglycemia in diabetes. In the current study, new molecules as a hybrid of isoxazole and dibenzazepine scaffolds were designed, based on their literature as antidiabetic agents. For this, a series of dibenzazepine-linked isoxazoles (33–54) was prepared using Nitrile oxide-Alkyne cycloaddition (NOAC) reaction, and evaluated for their α-glucosidase inhibitory activities to explore new hits for treatment of diabetes. Most of the compounds showed potent inhibitory potency against α-glucosidase (EC 3.2.1.20) enzyme (IC50 = 35.62 ± 1.48 to 333.30 ± 1.67 μM) using acarbose as a reference drug (IC50 = 875.75 ± 2.08 μM). Structure-activity relationship, kinetics and molecular docking studies of active isoxazoles were also determined to study enzyme-inhibitor interactions. Compounds 33, 40, 41, 46, 48–50, and 54 showed binding interactions with critical amino acid residues of α-glucosidase enzyme, such as Lys156, Ser157, Asp242, and Gln353.
- Umm-E-Farwa,Ullah, Saeed,Khan, Maria Aqeel,Zafar, Humaira,Atia-tul-Wahab,Younus, Munisaa,Choudhary, M. Iqbal,Basha, Fatima Z.
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supporting information
(2021/05/10)
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- Electrochemical synthesis of 1,2,4-oxadiazoles from amidoximes through dehydrogenative cyclization
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A convenient and efficient method for the generation of the iminoxy radical through anodic oxidation was developed for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles fromN-benzyl amidoximes. The transformation proceeds through 1.5-Hydrogen Atom Transfer (1,5-HAT) and intramolecular cyclization. The process features simple operation, mild conditions, broad substrate scope and high functional group compatibility, and provides a facile and practical way for the preparation of 1,2,4-oxadiazoles.
- Hu, Aixi,Jiang, chan,Li, mingfang,Xu, Leitao,Ye, Jiao,Yi, Yangjie
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supporting information
p. 10611 - 10616
(2021/12/27)
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- Identification of morpholine based hydroxylamine analogues: Selective inhibitors of MARK4/Par-1d causing cancer cell death through apoptosis
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Microtubule affinity-regulating kinase 4 (MARK4) is a serine/threonine kinase involved in the phosphorylation of MAP proteins that regulates microtubule dynamics and abets tumor progression by participating in oncogenic signaling pathways. It is overexpressed in multiple human malignancies and no drug is available for this potential therapeutic target at present. Therefore, using the structure based drug design strategy, a library of hydroxylamine derivatives of morpholine were designed and synthesized as small molecule inhibitors of MARK4. Compound 32 having the CF3 group at the ortho position of the phenyl ring tethered with the >CNOH core and the hinge binder morpholine component was found to be a potent and selective inhibitor of MARK4 over thirty other serine-threonine kinases. Study of cell viability and compound induced morphological changes in MCF-7 cancer cells discovered that molecule 32 caused death of cancerous cells through the mechanism of apoptosis. Compound 32 may be transported and delivered to the target site through the blood stream, and has promising antioxidant potential. Such bio-active molecules could serve as optimized lead candidates in drug discovery for cancer treatment through MARK4 inhibition.
- Avecilla, Fernando,Azam, Amir,Gaur, Aysha,Hassan, Md. Imtaiyaz,Khan, Nashrah Sharif,Khan, Parvez,Peerzada, Mudasir Nabi
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supporting information
p. 16626 - 16637
(2020/10/14)
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- Design, Synthesis and Characterization of Novel Isoxazole Tagged Indole Hybrid Compounds
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Sixteen new isoxazole tagged indole compounds have been synthesized via copper (I) catalyzed click chemistry of the aryl hydroxamoyl chloride and an indole containing alkyne moiety. The chemical structure of the synthesized compounds has been established using various physicochemical techniques. X-ray single crystal analysis of Ethyl 1-((3-phenylisoxazol-5-yl) methyl)-1H-indole-2-carboxylate (8a) has been analyzed. All compounds were tested for their antibacterial and anticancer activities. The activities for the new compounds were weak against both bacterial strains and the cancer cell lines.
- Al-Qawasmeh, Raed A.,Al-Nazer, Louy A.,Dawlat-Kari, Sarah A.,Abu-Qatouseh, Luay,Sabri, Salim S.,Aldamen, Murad A.,Sinnokrot, Mutasem
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p. 138 - 148
(2020/04/15)
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- Design, Synthesis, Molecular Docking Studies, and Biological Evaluation of Pyrazoline Incorporated Isoxazole Derivatives
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Abstract: A novel series of pyrazoline incorporated isoxazole derivatives were designed and synthesized. The synthesized compounds were characterized by 1H NMR, IR and ESI-MS spectra. In addition, all the synthesized compounds were docked with
- Radhika,Vijay,Harinadha,Madhavareddy
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p. 429 - 437
(2020/07/02)
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- Design, synthesis and evaluation of novel levoglucosenone derivatives as promising anticancer agents
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A series of levoglucosenone-derived 1,2,3-triazoles and isoxazoles featuring a flexible spacer between the heteroaromatic and anhydropyranose cores have been designed and synthesized following an hetero Michael // 1,3-dipolar cycloaddition path. The use o
- Borini Etichetti, Carla M.,Cicetti, Soledad,Girardini, Javier E.,Sarotti, Ariel M.,Spanevello, Rolando A.,Suárez, Alejandra G.,Tsai, Yi-hsuan
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supporting information
(2020/06/03)
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- Discovery of Natural Product-Based Fungicides (II): Semisynthesis and Biological Activity of Sarisan Attached 3-Phenylisoxazolines as Antifungal Agents
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Many phytopathogenic fungi cause severe damage to crop yields. In continuation of our research aimed at the discovery and development of natural products-based fungicides, a series of thirty-one sarisan attached 3-phenylisoxazolines were synthesized and evaluated for their antifungal activities against five phytopathogenic fungi (B. cinerea, C. lagenarium, A. solani, F. solani, and F. graminearum). Among all title sarisan derivatives, compounds IV2, IV14 and IV23 showed potent antifungal activity against some phytopathogenic fungi. In particular, compound IV2 exhibited a broad-spectrum and more potent antifungal activity against A. solani, F. solani, and F. graminearum than the commercial fungicide Hymexazol. In addition, compounds IV2, IV14 and IV23 also displayed relative low toxicity on normal NRK-52E cells. This work will give some insights into the development of sarisan derivatives as new fungicide candidates in plant protection.
- Liu, Zhiyan,Cao, Jiangping,Yan, Xiaoting,Cheng, Wanqing,Wang, Xiaoguang,Yang, Ruige,Guo, Yong
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- Translational impact of novel widely pharmacological characterized mofezolac-derived COX-1 inhibitors combined with bortezomib on human multiple myeloma cell lines viability
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A set of novel diarylisoxazoles has been projected using mofezolac (1) as a lead compound to investigate structure-inhibitory activity relationships of new compounds and the cyclooxygenases (COXs) catalytic activity. Mofezolac was chosen because is the mo
- Pati, Maria Laura,Vitale, Paola,Ferorelli, Savina,Iaselli, Mariaclara,Miciaccia, Morena,Boccarelli, Angelina,Di Mauro, Giuseppe Davide,Fortuna, Cosimo G.,Souza Domingos, Thaisa Francielle,Rodrigues Pereira da Silva, Luiz Cláudio,de Pádula, Marcelo,Cabral, Lucio Mendes,Sathler, Plínio Cunha,Vacca, Angelo,Scilimati, Antonio,Perrone, Maria Grazia
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- Synthesis method of parecoxib sodium isomeric impurities
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The invention provides a synthesis method of parecoxib sodium isomeric impurities. Structures of the parecoxib sodium isomeric impurities are shown in formulae I and II in the description. The synthesis method comprises the following steps: the compound as shown in the formula I is subjected to reaction with the compound as shown in formula II or the compound as shown in formula III under the action of alkali, and a compound as shown in formula IV is generated; the corresponding parecoxib sodium isomeric impurities are generated by reduction reaction, diazotization, sulfonylation, amino substitution reaction and acylation reaction; the total reaction yield is higher than 22%, and purity of a target product is higher than 99%.
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Paragraph 0205; 0213-0219
(2019/01/23)
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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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- Simple one-pot synthesis of 5-(chloromethyl)isoxazoles from aldoximes and 2,3-dichloro-1-propene
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[Figure not available: see fulltext.] A one-pot synthesis of 3-substituted 5-chloromethylisoxazoles from available starting aldoximes and 2,3-dichloro-1-propene, serving both as a solvent and reagent, is proposed. Excess 2,3-dichloro-1-propene is recovered after the reaction. The synthesis is effective for oximes of both aromatic and aliphatic aldehydes.
- Kondrashov, Evgeniy V.,Shatokhina, Nina S.
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p. 1228 - 1232
(2020/01/08)
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- Copper-catalysed synthesis of 3,5-disubstituted isoxazoles enabled by pyridinyl benzimidazol (PBI) as a bidentate N-chelating ligand under mild conditions
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In this paper, we introduced pyridinyl benzimidazol (PBI) as an easy-to-handle and bidentate N-chelating ligand that promote clean synthesis of 3,5-disubstituted isoxazoles in the presence of copper acetate as catalyst. This catalytic approach initiates with the hydroxyamination of aldehydes followed by chlorination and then generation of nitrile oxide which subsequently undergoes click-type [3?+?2]-dipolar cycloaddition with alkynes to give isoxazoles. This method provides an alternative green process to construct isoxazole derivatives.
- Khalifeh, Reza,Shahriarpour, Fatemeh,Sharghi, Hashem,Aberi, Mahdi
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p. 813 - 821
(2018/03/01)
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- Tandem Condensation/Rearrangement Reaction of 2-Aminohetarene N-Oxides for the Synthesis of Hetaryl Carbamates
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A new approach to hetaryl carbamates through a tandem condensation/rearrangement reaction of 2-aminohetarene N-oxides was developed. The developed reaction is suitable for both five- and six-membered heterocycles and proceeds through the condensation of 2
- Bystrov, Dmitry M.,Zhilin, Egor S.,Fershtat, Leonid L.,Romanova, Anna A.,Ananyev, Ivan V.,Makhova, Nina N.
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supporting information
p. 3157 - 3163
(2018/08/24)
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- In Vitro, In Silico, and In Vivo Analyses of Novel Aromatic Amidines against Trypanosoma cruzi
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Five bis-arylimidamides were assayed as anti-Trypanosoma cruzi agents by in vitro, in silico, and in vivo approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested in vivo led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5 days intraperitoneally) but without mortality protection. In silico target fishing suggested DNA as the main target, but ultrastructural data did not match.
- Santos, Camila C.,Lionel, Jéssica R.,Peres, Raiza B.,Batista, Marcos M.,Da Silva, Patrícia B.,De Oliveira, Gabriel M.,Da Silva, Cristiane F.,Batista, Denise G. J.,Souza, Sandra Maria O.,Andrade, Carolina H.,Neves, Bruno J.,Braga, Rodolpho C.,Patrick, Donald A.,Bakunova, Svetlana M.,Tidwell, Richard R.,Soeiro, Maria de Nazaré C.
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supporting information
(2018/02/06)
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- An Efficient One–pot Procedure for the Direct Preparation of 4,5-Dihydroisoxazoles from Amides
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A Mo(CO)6 (molybdenumhexacarbonyl) catalyzed reductive functionalization of amides to afford 5-amino substituted 4,5-dihydroisoxazoles is presented. The reduction of amides generates reactive enamines, which upon the addition of hydroximinoyl chlorides and base undergoes a 1,3-dipolar cycloaddition reaction that gives access to the desired heterocyclic compounds. The transformation of amides is highly chemoselective and tolerates functional groups such as nitro, nitriles, esters, and ketones. Furthermore, a versatile scope of 4,5-dihydroisoxazoles derived from a variety of hydroximinoyl chlorides and amides is demonstrated. (Figure presented.).
- Slagbrand, Tove,Kervefors, Gabriella,Tinnis, Fredrik,Adolfsson, Hans
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supporting information
p. 1990 - 1995
(2017/06/09)
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- Design and synthesis of a new series of 3,5-disubstituted isoxazoles active against Trypanosoma cruzi and Leishmania amazonensis
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Chagas disease and leishmaniasis are neglected tropical diseases (NTDs) endemic in developing countries. Although there are drugs available for their treatment, efforts on finding new efficacious therapies are continuous. The natural lignans grandisin (1)
- da Rosa, Rafael,de Moraes, Milene H?ehr,Zimmermann, Lara Almida,Schenkel, Eloir Paulo,Steindel, Mario,Bernardes, Lílian Sibelle Campos
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- Design, synthesis, and in vitro evaluation of novel antifungal triazoles
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Twenty-nine novel triazole analogues of ravuconazole and isavuconazole were designed and synthesized. Most of the compounds exhibited potent in vitro antifungal activities against 8 fungal isolates. Especially, compounds a10, a13, and a14 exhibited superior or comparable antifungal activity to ravuconazole against all the tested fungi. Structure-activity relationship study indicated that replacing 4-cyanophenylthioazole moiety of ravuconazole with fluorophenylisoxazole resulted in novel antifungal triazoles with more effectiveness and a broader-spectrum.
- Xie, Fei,Ni, Tingjunhong,Zhao, Jing,Pang, Lei,Li, Ran,Cai, Zhan,Ding, Zichao,Wang, Ting,Yu, Shichong,Jin, Yongsheng,Zhang, Dazhi,Jiang, Yuanying
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supporting information
p. 2171 - 2173
(2017/04/28)
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- Triazole alcohol derivative and preparation method and application thereof
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The invention relates to a triazole alcohol derivative and a preparation method and application thereof. The chemical structure of the triazole alcohol derivative is as shown in the formula I. The invention also provides salt of the compound, a pharmaceutical composition, a preparation method and application. The compound of the invention has strong antifungal activity, has advantages of low toxicity and wide antimicrobial spectrum, and can be used for preparation of antifungal drugs.
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Paragraph 0204
(2017/06/28)
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- Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions
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[3+2] reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn(OAc)3 mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogues of isoCA-4 were synthesized as inhibitors of tubulin polymerization. Among them, compound 6g was found to be the most potent cytotoxic agents against PC-3 cells with IC50 value of 0.47 μM, and compound 5p exhibted highest activity on HeLa cells with IC50 vaule of 2.32 μM. Tubulin polymerization assay revealed that 6g was a dose-dependent and effective inhibitor of tubulin assembly. Immunohistochemistry studies and cell cycle distribution analysis indicated that 6g severely disrupted microtubule network and significantly arrested most cells in the G2/M phase of the cell cycle in PC-3 cells. In addition, molecular docking studies showed that two chiral isomers of 6g can bind efficiently and similarly at colchicine binding site of tubulin.
- Song, Ming-Yu,Cao, Chen-Yu,He, Qiu-Rui,Dong, Qing-Miao,Li, Ding,Tang, Jiang-Jiang,Gao, Jin-Ming
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p. 5290 - 5302
(2017/10/06)
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- USE OF DDX3 INHIBITORS AS ANTIPROLIFERATIVE AGENTS
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The present invention refers to compounds of formula I or II endowed with DDX3 inhibitory activity, relative pharmaceutical compositions and their use as antihyperproliferative agents. (I) or (II)
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(2017/10/30)
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- Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition
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Glycogen phosphorylase (GP) is a target for the treatment of hyperglycaemia in the context of type 2 diabetes. This enzyme is responsible for the depolymerization of glycogen into glucose thereby affecting the levels of glucose in the blood stream. Twelve
- Goyard, David,Kónya, Bálint,Chajistamatiou, Aikaterini S.,Chrysina, Evangelia D.,Leroy, Jérémy,Balzarin, Sophie,Tournier, Michel,Tousch, Didier,Petit, Pierre,Duret, Cédric,Maurel, Patrick,Somsák, László,Docsa, Tibor,Gergely, Pál,Praly, Jean-Pierre,Azay-Milhau, Jacqueline,Vidal, Sébastien
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supporting information
p. 444 - 454
(2015/12/24)
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- Regio-and stereoselective synthesis of pregnane-fused isoxazolines by nitril-oxide/alkene 1,3-dipolar cycloaddition and an evaluation of their cell-growth inhibitory effect in vitro
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Efficient syntheses of some pregnane-fused isoxazolines from 16-dehydropregnenolone acetate with different arylnitrile oxides were carried out by 1,3-dipolar cycloadditions. The intermolecular ring-closures occurred in a highly regio- and stereoselective manner permitting the formation of a single 16α,17α-condensed diastereomer in which the O terminus of the nitrile oxide dipole is attached to C-17 of the sterane core. The conversions were found to be affected significantly by the electronic character of the substituents on the aromatic moiety of the 1,3-dipoles. Deacetylation of the primary products resulted in the corresponding 3β-OH analogs. All of the synthesized compounds were subjected to in vitro pharmacological studies for the determination of their antiproliferative effects on four breast cancer cell lines (MCF7, T47D, MDA-MB-231 and MDA-MB-361).
- Mótyán, Gergo,Baji, ádám,Zupkó, István,Frank, éva
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p. 143 - 149
(2016/02/05)
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- Easy Access to 1-Amino and 1-Carbon Substituted Isoquinolines via Cobalt-Catalyzed C - H/N - O Bond Activation
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A green atom-economical method for the synthesis of highly functionalized 1-amino and 1-carbon substituted isoquinolines from the reaction of N′-hydroxybenzimidamides and aryl ketoximes, respectively, with alkynes via pentamethylcyclopentadienylcobalt(III)-catalyzed C - H/N - O bond activation is described. The external oxidant-free annulation reaction uses the =NOH moiety in N′-hydroxybenzimidamides or N-aromatic ketone oximes as the directing group and internal oxidant. This first row transition metal-catalyzed annulation serves as an efficient alternative for the synthesis of isoquinolines, as water is the only by-product and expensive noble metals such as rhodium(III), iridium(III), palladium(II), and ruthenium(II) are not required. The reaction proceeds via C - H activation, alkyne insertion, reductive elimination, and N - O activation.
- Muralirajan, Krishnamoorthy,Kuppusamy, Ramajayam,Prakash, Sekar,Cheng, Chien-Hong
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supporting information
p. 774 - 783
(2016/03/09)
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- Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles
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Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4-5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five- and six-membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having a unique hybrid isoxazoline-oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly-like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.
- Kesornpun, Chatchai,Aree, Thammarat,Mahidol, Chulabhorn,Ruchirawat, Somsak,Kittakoop, Prasat
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supporting information
p. 3997 - 4001
(2016/03/19)
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- FeCl3·6H2O-mediated reaction of [60]fullerene with amidoximes
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A FeCl3·6H2O-mediated reaction of [60]fullerene with amidoximes for the preparation of fulleroimidazolines has been presented. This reaction shows a wide substrate scope, and the products obtained from alkyl-substituted amidoximes ar
- Fang, Fang,Zhang, Jianmin,Cao, Lei,Shen, Subo,Guo, Yuwei,He, Zhiqing,Hu, Han
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supporting information
p. 2476 - 2480
(2016/04/26)
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- Synthesis, characterization, antimicrobial activity, and QSAR studies on substituted oxadiazaboroles
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This paper presents the synthesis and in vitro antimicrobial activity studies of 3,4,5-trisubstituted 4,5-dihydro-1,2,4,5-oxadiazaboroles (4) and 3,5-disubstituted 4,5-dihydro-1,2,4,5-oxadiazaboroles (7). The antimicrobial activities of the compounds were
- Pir, Meryem,Agirbas, Hikmet,Budak, Fatma,Ilter, Merve
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p. 1794 - 1812
(2016/10/03)
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- HUMAN HELICASE DDX3 INHIBITORS AS THERAPEUTIC AGENTS
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The present invention refers to compounds endowed with RNA helicase DDX3 inhibitory activity of formula I and II and their therapeutic use, in particular for the treatment of viral diseases.
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Page/Page column 95; 96
(2016/09/22)
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- Büchwald-Hartwig Reaction Applied to Synthesis of New Luminescent Liquid Crystal Triarylamines Derived from Isoxazoles
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The present work describes the synthesis and characterization of novel series of triarylamines isoxazoles (TAA) addressed to the organic photovoltaic materials. Diarylisoxazoles were synthesized by sequential [3+2] 1,3-dipolar cycloaddition reaction betwe
- Vilela,Fernandes,Kelly,Merlo
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p. 169 - 182
(2015/07/15)
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- 3,5-diarylisoxazoles: A New Entry to Soft Crystal Phase
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This work describes the synthesis and characterization of a new liquid-crystalline compounds based on isoxazoles. Classical synthetic methodologies were employed in the preparation of this compounds, and the [3+2] 1,3-dipolar cycloaddition was the key ste
- Da Rosa, Rafaela R.,Brose, Irwing S.,Vilela, Guilherme D.,Merlo, Aloir A.
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p. 158 - 168
(2015/07/15)
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- Design, synthesis and evaluation of N-substituted saccharin derivatives as selective inhibitors of tumor-associated carbonic anhydrase XII
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A series of N-alkylated saccharin derivatives were synthesized and tested for the inhibition of four different isoforms of human carbonic anhydrase (CA, EC 4. 2.1.1): the transmembrane tumor-associated CA IX and XII, and the cytosolic CA I and II. Most of the reported derivatives inhibited CA XII in the nanomolar/low micromolar range, hCA IX with KIs ranging between 11 and 390 nM, whereas they were inactive against both CA I (KIs >50 μM) and II (KIs ranging between 39.1 nM and 50 μM). Since CA I and II are off-targets of antitumor carbonic anhydrase inhibitors (CAIs), the obtained results represent an encouraging achievement for the development of new anticancer candidates without the common side effects of non-selective CAIs. Moreover, the lack of an explicit zinc binding function on these inhibitors opens the way towards the exploration of novel mechanisms of inhibition that could explain the high selectivity of these compounds for the inhibition of the transmembrane, tumor-associated isoforms over the cytosolic ones.
- D'Ascenzio, Melissa,Carradori, Simone,De Monte, Celeste,Secci, Daniela,Ceruso, Mariangela,Supuran, Claudiu T.
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p. 1821 - 1831
(2014/03/21)
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- Synthesis and evaluation of cyclohexane carboxylic acid head group containing isoxazole and thiazole analogs as DGAT1 inhibitors
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Diacylglycerol acyltransferase 1 (DGAT1) is known to play an important catalytic role in the final step of triglyceride biosynthesis. High fat diet fed DGAT1 knockout mice were resistant to weight gain and exhibited increased insulin and leptin sensitivity thereby indicating a plausible role for DGAT1 inhibitors in the treatment of obesity. 4-Phenylpiperidine-1-carbonyl cyclohexanecarboxylic acid (compound 6, DGAT1 IC50 = 57 nM) has been lately reported as a potent DGAT1 inhibitor. In our search for newer scaffolds possessing potent DGAT1 activity we undertook a systematic diversification of compound 6 to identify a 4-(5-phenylthiazole-2-carboxamido)cyclohexanecarboxylic acid scaffold. Further linker optimization of this scaffold identified compound 9e (DGAT1 IC50 = 14.8 nM) as a potent DGAT1 inhibitor. Coupled with its in vitro potency, compound 9e also exhibited 112 percent plasma triglyceride reduction at a 3 mpk dose in an oral fat tolerance test (FTT) when studied in Swiss mice.
- Kandre, Shivaji,Bhagat, Pundlik Rambhau,Kumar Reddy, M. Mahesh,Dalal, Roda,Dixit, Amol,Deshmukh, Nitin J.,Anthony, Jessy,Bose, Julie,Anupindi, Raghuram,Sharma, Rajiv,Gupte, Amol
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p. 203 - 215
(2014/05/06)
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- Practical synthesis of N -substituted cyanamides via tiemann rearrangement of amidoximes
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A facile and general synthesis of various N-substituted cyanamides was accomplished by the Tiemann rearrangement of amidoximes with benzenesulfonyl chlorides (TsCl or o-NsCl) and DIPEA.
- Lin, Chia-Chi,Hsieh, Tsung-Han,Liao, Pen-Yuan,Liao, Zhen-Yuan,Chang, Chih-Wei,Shih, Yu-Chiao,Yeh, Wen-Hsiung,Chien, Tun-Cheng
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supporting information
p. 892 - 895
(2014/03/21)
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- Synthesis and characterization of para-substituted N,N′- dihydroxybenzamidines and their derivatives as model compounds for a class of prodrugs
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A synthetic strategy for previously unknown para-substituted N,N′-dihydroxybenzamidines and their O-monosubstituted and O,O′-disubstituted methyl, benzyl, and tetrahydropyranyl derivatives is described. The procedure starts with the corresponding hydroxam
- Schwarz, Laura,Girreser, Ulrich,Clement, Bernd
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p. 1961 - 1975
(2014/04/03)
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- Synthesis of heterocycle-tethered acylbenzofurans and benzodifurans from odorless and recyclable organoseleno polystyrene resin
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Organoseleno polystyrene resin-supported synthesis provided quick access to a series of acylbenzofuran derivatives tethered to isoxazoles, triazoles and isoxazolines as well as benzodifurans. Although this methodology proceeded through multiple steps such
- Wang, Yuguang,Zhu, Bingchun,Xu, Qing,Zhu, Qing,Yu, Lei
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p. 49170 - 49179
(2014/12/10)
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- Synthesis and Characterization of para-Substituted N,N′-Dihydroxybenzamidines and Their Derivatives as Model Compounds for a Class of Prodrugs
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A synthetic strategy for previously unknown para-substituted N,N′-dihydroxybenzamidines and their O-monosubstituted and O,O′-disubstituted methyl, benzyl, and tetrahydropyranyl derivatives is described. The procedure starts with the corresponding hydroxam
- Schwarz, Laura,Girreser, Ulrich,Clement, Bernd
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p. 1961 - 1975
(2015/10/05)
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- Larvicidal isoxazoles: Synthesis and their effective susceptibility towards Aedes aegypti larvae
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Twenty 3,5-disubstituted isoxazoles have been synthesized and tested against fourth instar Aedes aegypti larvae. In the synthesis of title compounds, modifications have been made in the C-5 side-chain with a view to test their larvicidal activity. These i
- Da Silva-Alves, Diana C.B.,Dos Anjos, Janaina V.,Cavalcante, Nery N.M.,Santos, Geanne K.N.,Navarro, Daniela M.Do A.F.,Srivastava, Rajendra M.
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supporting information
p. 940 - 947
(2013/03/14)
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- Facile synthesis of 3-aryl-5-(2-oxopyrrolidin-1-yl)-and 5-(pyridin-4-yl)-4,5-dihydroisoxazoles via 1,3-dipolar cycloaddition under mild conditions
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A convenient and efficient synthetic approach for the synthesis of 5-substituted 3-aryl-4,5-dihydroisoxazoles is reported. In the presence of triethylamine, a series of hydroximoyl chlorides were transformed into nitrile oxides, followed by reaction with N-vinyl-2-pyrrolidinone (or 4-vinylpyridine) by a 1,3-dipolar cycloaddition to give novel 4,5-dihydroisoxazole derivatives.
- Gong, Yan,Wang, Yong,Zhao, Wen-Tao,Tang, Xiang-Yang
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p. 499 - 502
(2013/09/12)
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