- Synthesis of 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazol-5(4H)-one and 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazole-5(4H)-thione and solvent effects on their infrared spectra in organic solvents
-
In the present study novel 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazol-5(4H)-one (compound (4)) and 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazole-5(4H)-thione (compound (5)) were synthesized. These oxadiazole ring derivatives were cha
- Kara, Yesim S.,ünsal, Mustafa,Tekin, Nalan,E?me, Asl?
-
-
Read Online
- Design and synthesis of sinomenine isoxazole derivatives via 1,3-dipolar cycloaddition reaction
-
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
-
p. 2360 - 2364
(2019/11/11)
-
- Design, synthesis, in vitro and in silico evaluation of new 3-phenyl-4,5-dihydroisoxazole-5-carboxamides active against drug-resistant mycobacterium tuberculosis
-
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
-
-
- Ru-Catalyzed [3 + 2] Cycloaddition of Nitrile Oxides and Electron-Rich Alkynes with Reversed Regioselectivity
-
Polarity reversal ("umpolung") of a functional group can override its inherent reactivity and lead to distinct bond-forming modes. Herein we describe a rarely studied cycloaddition between nitrile oxides and electron-rich alkynes with reversed regioselect
- Feng, Qiang,Huang, Hai,Sun, Jianwei
-
p. 2431 - 2436
(2021/05/05)
-
- Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
-
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.
-
-
- Construction of spiro-1,2,4-oxadiazoline-fused matrine-type alkaloids as pesticidal agents
-
In order to increase the agricultural properties of matrine, a series of novel matrine-type alkaloids containing spiro-1,2,4-oxadiazoline fragment at the C-15 position were prepared. Eight target molecules were elucidated by X-ray single-crystal diffracti
- Lv, Min,Ma, Qianjun,Xu, Hui,Zhang, Shaoyong
-
-
- Triazole alcohol derivative as well as preparation method and application thereof
-
The invention relates to a triazole alcohol derivative as well as a preparation method and application thereof. The chemical structure of the triazole alcohol derivative is shown as a formula I, R1 represents a benzene ring or a substituted benzene ring, and substituent groups of the substituted benzene ring can be located at all positions of the benzene ring, can be mono-substituted or multi-substituted, and can be selected from a) halogen which is F and Cl; b) an electron withdrawing group which is cyano or trifluoromethyl; c ) a lower alkyl of 1-4 carbon atoms or a halogen substituted loweralkyl; and d) lower alkoxy of 1-4 carbon atoms or halogen substituted lower alkoxy. The compound of the invention has strong antifungal activity, has the advantages of low toxicity, wide antibacterial spectrum and the like, and can be used for preparing antifungal drugs.
- -
-
-
- Design, synthesis, and in vitro evaluation of novel triazole analogues featuring isoxazole moieties as antifungal agents
-
In order to develop novel antifungal agents, based on our previous work, a series of (2R,3R)-3-((3-substitutied-isoxazol-5-yl)methoxy)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol (a1-a26) were designed and synthesized. All of the compounds exhibited good in vitro antifungal activities against eight human pathogenic fungi. Among them, compound a6 showed excellent inhibitory activity against Candida albicans and Candida parasilosis with MIC80 values of 0.0313 μg/mL. In addition, compounds a6, a9, a12, a13 and a14 exhibited moderate inhibitory activities against fluconazole-resistant isolates with MIC80 values ranging from 8 μg/mL to 16 μg/mL. Furthermore, compounds a6, a12 and a23 exhibited low inhibition profiles for CYP3A4. Clear SARs were analyzed, and the molecular docking experiment was carried out to further investigate the relationship between a6 and the target enzyme CYP51.
- Chai, Xiaoyun,Ding, Zichao,Hao, Yumeng,Jiang, Yuanying,Jin, Yongsheng,Ni, Tingjunhong,Wang, Ruilian,Wang, Ruina,Wang, Ting,Xie, Fei,Yu, Shichong,Zhang, Dazhi
-
-
- Identification of morpholine based hydroxylamine analogues: Selective inhibitors of MARK4/Par-1d causing cancer cell death through apoptosis
-
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
-
p. 16626 - 16637
(2020/10/14)
-
- Discovery of Natural Product-Based Fungicides (II): Semisynthesis and Biological Activity of Sarisan Attached 3-Phenylisoxazolines as Antifungal Agents
-
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
-
-
- Design, Synthesis and Characterization of Novel Isoxazole Tagged Indole Hybrid Compounds
-
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
-
p. 138 - 148
(2020/04/15)
-
- Reaction of Aldoximes with Sodium Chloride and Oxone under Ball-Milling Conditions
-
The solvent-free mechanochemical reaction has aroused increasing interest among scientists. Mechanical ball-milling can implement reactions under mild conditions, shorten the reaction time, and improve the reaction efficiency. Particularly, the most attractive characteristic of mechanochemistry is that it can alter the reaction pathway. However, few such examples have been reported so far. In this paper, we report the reaction of aldoximes with NaCl and Oxone under ball-milling conditions to afford N-acyloxyimidoyl chlorides, which are different from those of the liquid-phase counterpart.
- Chen, Kuan,Niu, Chuang,Wang, Guan-Wu
-
-
- Leaving Group Assisted Strategy for Photoinduced Fluoroalkylations Using N-Hydroxybenzimidoyl Chloride Esters
-
Redox-active esters (RAEs) as alkyl radical precursors have been extensively developed for C?C bond formations. However, the analogous transformations of fluoroalkyl radicals from the corresponding acid or ester precursors remain challenging because of the high oxidation potential of the fluoroalkyl carboxylate anions. The newly developed N-hydroxybenzimidoylchloride (NHBC) ester provides a general leaving group assisted strategy to generate a portfolio of fluoroalkyl radicals, and can be successfully applied in photoinduced decarboxylative hydrofluoroalkylation and heteroarylation of unactivated olefins. In addition, DFT calculations revealed that the NHBC ester proceeds by the fluorocarbon radical pathway, whereas other well-known RAEs proceed by the nitrogen radical pathway.
- Zhang, Weigang,Zou, Zhenlei,Wang, Yuanheng,Wang, Yi,Liang, Yong,Wu, Zhengguang,Zheng, Youxuan,Pan, Yi
-
supporting information
p. 624 - 627
(2018/12/13)
-
- Terminal Alkyne-Assisted One-Pot Synthesis of Arylamidines: Carbon Source of the Amidine Group from Oxime Chlorides
-
A terminal alkyne-assisted protocol for the one-pot formation of a diverse range of arylamidines from a novel cascade reaction of in situ generated nitrile oxides, sulfonyl azides, terminal alkynes, and water by [3 + 2] cycloaddition and ring opening sequ
- Yi, Fengping,Sun, Qihui,Sun, Jing,Fu, Chao,Yi, Weiyin
-
supporting information
p. 6780 - 6787
(2019/06/14)
-
- Facile One-Pot Transformation of Primary Alcohols into 3-Aryl- and 3-Alkyl-isoxazoles and -pyrazoles
-
Various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylisoxazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, NH 2 OH, and then NCS, followed by reaction with alkynes in the presence of Et 3 N. Similarly, various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylpyrazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, PhNHNH 2, and then NCS and decyl methyl sulfide, followed by reaction with alkynes in the presence of Et 3 N. Thus, both 3-aryl- and 3-alkylisoxazoles, and 3-aryl- and 3-alkylpyrazoles could be prepared from readily available primary alcohols in one pot under transition-metal-free conditions.
- Kobayashi, Eiji,Togo, Hideo
-
p. 3723 - 3735
(2019/09/30)
-
- Substituent effect study on the experimental 13C NMR chemical shifts of 3-(substituted phenyl)-3a,4,8,8a-tetrahydro-1,3-dioxepino[5,6-d] [1,2] isoxazoles
-
Novel heterocyclic derivatives containing isoxazole ring were synthesized by the 1,3-dipolar cycloaddition reaction of substituted nitrile oxides with cis-4,7-dihydro-1,3-dioxepin in the present study. These 3-(substituted phenyl)-3a,4,8,8a-tetrahydro-1,3
- Kara, Yesim S.,Yalduz, Sümeyye
-
p. 158 - 165
(2019/05/22)
-
- Stereospecific 1,4-Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes
-
Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N-oxides, and amides having a single configuration.
- Yang, Kai,Zhang, Feng,Fang, Tongchang,Zhang, Guan,Song, Qiuling
-
p. 13421 - 13426
(2019/08/20)
-
- Iodine Promoted One-Pot Synthesis of 2-Aryl Benzoxazoles from Amidoximes via Oxidative Cyclization and Ring Contraction
-
A molecular I2-promoted one-pot synthesis of 2-aryl benzoxazoles has been developed by using amidoximes rather than the limited 2-aminophenols or 2-haloamides as substrates. The amidoxime substrates provided unique and efficient strategies for converting readily available aniline and benzaldehyde precursors into valuable chemicals. This transformation proceeded smoothly under transition-metal-free conditions through a sequential oxidative cyclization and ring contraction, and provided a potential route for introducing certain groups at any site of the scaffold.
- Zhang, Yong,Ji, Min
-
p. 7506 - 7510
(2019/11/28)
-
- Design, docking and synthesis of novel bromo isatin incorporated isoxazole derivatives as vegfr-2 inhibitors
-
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.
-
-
- Synthesis and biological evaluation of novel 1-(aryl-aldehyde-oxime)uracil derivatives as a new class of thymidine phosphorylase inhibitors
-
A novel series of 1-(aryl aldehyd oxime) uracil derivatives were synthesized, characterized and evaluated for its inhibitory activity against thymidine phosphorylase. Among them, the compound 8d, 8e, 8f, 8g and 8l displayed potent thymidine phosphorylase
- Zhao, Shuyue,Li, Ke,Jin, Yi,Lin, Jun
-
-
- Copper-catalysed synthesis of 3,5-disubstituted isoxazoles enabled by pyridinyl benzimidazol (PBI) as a bidentate N-chelating ligand under mild conditions
-
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
-
p. 813 - 821
(2018/03/01)
-
- Synthesis of novel isoxazoline-containing podophyllotoxin/2′(2′,6′)-(di)halogenopodophyllotoxin derivatives and their insecticidal/acaricidal activities
-
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
-
p. 1410 - 1416
(2018/03/21)
-
- Efficient synthesis of 1,2,4-oxadiazine-5-ones via [3+3] cycloaddition of in situ generated aza-oxyallylic cations with nitrile oxides
-
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
-
p. 2018 - 2020
(2018/04/25)
-
- A versatile strategy for the synthesis of 4,5-dihydroxy-2,3-pentanedione (DPD) and related compounds as potential modulators of bacterial quorum sensing
-
Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.
- Stotani, Silvia,Gatta, Viviana,Medda, Federico,Padmanaban, Mohan,Karawajczyk, Anna,Tammela, P?ivi,Giordanetto, Fabrizio,Tzalis, Dimitrios,Collina, Simona
-
-
- Synthesis of Tricyclic Isoxazoles via Sequential [3+2] Dipolar Cycloaddition and Palladium-Catalyzed Intramolecular Arylation Reactions
-
An efficient synthetic route to tricyclic isoxazoles via sequential copper-catalyzed 1,3-dipolar cycloaddition and palladium-catalyzed intramolecular arylation of isoxazoles is described. Based on these reactions, a convenient one-pot synthesis of the tri
- Guo, Dong-Cai,Zhang, Chao,Li, Fei,Zhang, Fenghua,Yu, Fang,He, Yu-Peng
-
p. 1356 - 1370
(2017/03/11)
-
- Design, synthesis, and in vitro evaluation of novel antifungal triazoles
-
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
-
p. 2171 - 2173
(2017/04/28)
-
- Triazole alcohol derivative and preparation method and application thereof
-
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.
- -
-
-
- An Efficient One–pot Procedure for the Direct Preparation of 4,5-Dihydroisoxazoles from Amides
-
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
-
p. 1990 - 1995
(2017/06/09)
-
- Catalytic Enantioselective [3 + 2] Cycloaddition of α-Keto Ester Enolates and Nitrile Oxides
-
An enantioselective [3 + 2] cycloaddition reaction between nitrile oxides and transiently generated enolates of α-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxide-generation conditions. A versatile array of nitrile oxides and α-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reactions via O-imidoylation and hetero-[3 + 2] pathways.
- Bartlett, Samuel L.,Sohtome, Yoshihiro,Hashizume, Daisuke,White, Peter S.,Sawamura, Miki,Johnson, Jeffrey S.,Sodeoka, Mikiko
-
p. 8661 - 8666
(2017/07/06)
-
- Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions
-
[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
-
p. 5290 - 5302
(2017/10/06)
-
- 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
-
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
-
p. 6662 - 6668
(2017/10/23)
-
- Semisynthesis, an anti-inflammatory effect of derivatives of 1β-hydroxy alantolactone from inula britannica
-
1β-hydroxy alantolactone, a sesquiterpene lactone mainly isolated from Inula genus plants, exhibits potent anti-inflammatory and anticancer activities. In this work, 1β-hydroxy alantolactone was isolated and five derivatives were prepared through different reactions at the C1-OH and C13-methylene motifs. The structure-activity relationships (SAR) of anti-inflammatory effects against NO production in RAW264.7 cells showed that the α-methylene-butyrolactone motif was essential for NO production suppression and that retaining the C1-OH group can remarkably improve this effect. The NF-B signaling pathway plays a pivotal role in the regulation ofNOexpression. Moreover, the levels of p65 and p50 phosphorylation were investigated and active compound 1 inhibited phosphorylation of p65 and p50 in TNF-α-induced NF-κB signaling. Further molecular docking suggested that 1 may target the p65 of NF-κB.
- Chen, Lin,Zhang, Jian-Ping,Liu, Xin,Tang, Jiang-Jiang,Xiang, Ping,Ma, Xing-Ming
-
-
- Preparation technology for 3-aryl-4-nitro isoxazole compound
-
The invention discloses a preparation technology for a 3-aryl-4-nitro isoxazole compound. The preparation technology comprises the following steps: synthesizing a compound shown as formula II through the nucleophilic addition of hydroxylamine hydrochloride and the compound shown as formula I used as the raw material; acquiring the compound shown as formula III through the substitution reaction of the compound shown as formula II and N-chlorosuccinimide; preparing 1-dimethyl amino-2-nitro ethylene through the reaction of N,N-dimethylformamide dimethyl acetal and nitromethane used as the raw material; and acquiring a target product 3-aryl-4-nitro isoxazole compound through the cyclization reaction of the compound shown as formula III and 1-dimethyl amino-2-nitro ethylene. The raw materials in the synthesis route are low in cost and easily acquired, the operation condition is mild and is easily controlled, the product is easily purified and the preparation technology is a new method for synthesizing the 3-aryl-4-nitro isoxazole compound.
- -
-
-
- N-Allyl-substituted aminomethylene-1,1-bisphosphonates in 1,3-dipolar cycloaddition reaction with aromatic nitrile N-oxides
-
A reaction of N-allyl-substituted aminomethylene-1,1-bisphosphonates with aromatic nitrile N-oxides was used to obtain new aminomethylenebisphosphonates with one or two 3-arylisoxazoline rings at the nitrogen atom. NMR spectroscopy studies showed that the
- Bykhovskaya,Aladzheva,Brel
-
p. 1256 - 1260
(2017/12/02)
-
- 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
-
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
-
p. 143 - 149
(2016/02/05)
-
- FeCl3·6H2O-mediated reaction of [60]fullerene with amidoximes
-
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
-
p. 2476 - 2480
(2016/04/26)
-
- Cu(I) catalyzed microwave assisted telescopic synthesis of 3,5-disubstituted isoxazoles in green media
-
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
-
p. 5514 - 5517
(2016/11/19)
-
- Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition
-
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
-
supporting information
p. 444 - 454
(2015/12/24)
-
- Easy Access to 1-Amino and 1-Carbon Substituted Isoquinolines via Cobalt-Catalyzed C - H/N - O Bond Activation
-
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
-
supporting information
p. 774 - 783
(2016/03/09)
-
- Convenient modular construction of medicinally important 5-acylamino-4,5-dihydroisoxazoles featuring four elements of diversity
-
An efficient modular approach toward medicinally important 5-acylamino-4,5-isoxazolines via the 1,3-dipolar cycloaddition reaction of nitrile oxides and MCR-derived enamide building blocks is described. This approach results in isoxazolines containing four elements of diversity utilizing two practically simple synthetic operations.
- Kulyashova, Alexandra,Krasavin, Mikhail
-
supporting information
p. 4395 - 4397
(2016/09/13)
-
- Synthesis of 5-hetaryluracil derivatives via 1,3-dipolar cycloaddition reaction
-
1,3-Dipolar cycloaddition is a convenient method for construction of various heterocyclic systems. We applied this method for the synthesis 5-hetaryluracil derivatives where substituted uracils played the role of 1,3-dipoles or dipolarophiles. Treatment of the nitrile oxide derived from 5-formyluracil and substituted alkenes gave the appropriate 5-(4,5-dihydroisoxazol-3-yl)pyrimidine-2,4(1H,3H)-diones, which by oxidation with N-bromosuccinimide were transformed into appropriate 5-(isoxazol-3-yl)uracils. When 5-cyanouracil was used as a dipolarophile in the reaction with nitrile oxides, generated from aromatic aldoximes, several 5-(1,2,4-oxadiazol-5-yl)uracils were obtained. An alternative reaction of 5-formyluracil with an excess of nitriles in the presence of cerium ammonium nitrate as an oxidant gave 1,2,4-oxadiazol-3-yl derivatives in moderate yields. (Chemical Equation Presented).
- Jakubiec, Dominika,Przypis, ?ukasz,Suwiński, Jerzy W.,Walczak, Krzysztof Z.
-
p. 149 - 161
(2017/02/19)
-
- Side-chain prototropic tautomerism of 4-hydroxyfuroxans in methylation reactions
-
A general and simple method for the preparation of under explored 3-aryl-4-hydroxyfuroxans by nucleophilic substitution of the nitro group in 3-aryl-4-nitrofuroxans using NaOH in H2O-THF has been developed. The methylation of 3-aryl-4-hydroxyfu
- Fershtat, Leonid L.,Epishina, Margarita A.,Ovchinnikov, Igor V.,Struchkova, Marina I.,Romanova, Anna A.,Ananyev, Ivan V.,Makhova, Nina N.
-
supporting information
p. 5685 - 5689
(2016/11/28)
-
- Substituent effect study on experimental 13C NMR chemical shifts of (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene)diacetate derivatives
-
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.
-
p. 723 - 730
(2015/07/28)
-
- 3,5-diarylisoxazoles: A New Entry to Soft Crystal Phase
-
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.
-
p. 158 - 168
(2015/07/15)
-
- Synthesis of gem-bisphosphonates with (3-aryl-4,5-dihydroisoxazol-5-yl)methylamino moiety
-
Three-component reaction between N-allyl-N-methylamine, triethyl orthoformate and diethyl phosphite affords N-[bis(diethoxyphosphoryl)methyl]-N-methyl-3-arylprop-3-en-1-amine whose cycloaddition with nitrile N-oxides gives 5-{N-[bis(diethoxyphosphoryl)met
- Brel, Valery K.
-
p. 234 - 235
(2015/06/17)
-
- Reaction between (Z)-Arylchlorooximes and α-Isocyanoacetamides: A procedure for the synthesis of Aryl-α-ketoamide amides
-
(Z)-Arylchlorooximes and α-isocyanoacetamides undergo a smooth reaction to produce 1,3-oxazol-2-oxime derivatives in good yields. Opening of the oxazole ring and deoximation reaction give a facile access to aryl-α-ketoamide amides, a class of privileged s
- Giustiniano, Mariateresa,Mercalli, Valentina,Cassese, Hilde,Di Maro, Salvatore,Galli, Ubaldina,Novellino, Ettore,Tron, Gian Cesare
-
p. 6006 - 6014
(2014/07/21)
-
- Synthesis and evaluation of spiroisoxazoline oxindoles as anticancer agents
-
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.
-
p. 577 - 584
(2014/01/17)
-
- Practical synthesis of N -substituted cyanamides via tiemann rearrangement of amidoximes
-
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
-
p. 892 - 895
(2014/03/21)
-
- Synthesis and characterization of para-substituted N,N′- dihydroxybenzamidines and their derivatives as model compounds for a class of prodrugs
-
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
-
p. 1961 - 1975
(2014/04/03)
-
- Synthesis and Characterization of para-Substituted N,N′-Dihydroxybenzamidines and Their Derivatives as Model Compounds for a Class of Prodrugs
-
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
-
p. 1961 - 1975
(2015/10/05)
-