- Synthesis, characterization, antimicrobial activity, and QSAR studies of some new 6-substituted phenyl 3-(4-chlorophenyl)-3a,4,8,8a-tetrahydro-[1,3,2]dioxaborepino [5,6-d]isoxazoles
-
3-(4-Chlorophenyl)-3a,4,8,8a-tetrahydro-[1,3,2]dioxaborepino[5,6-d] isoxazoles were synthesized from the reaction of (3-(4-chlorophenyl)-4,5-dihydroisoxazole-4,5-diyl)dimethanol with substituted phenylboronic acids. Crystal structure of 1-(4-(3-(4-chlorophenyl)-3a,4,8,8a-tetrahydro-[1,3,2]dioxaborepino[5,6-d]isoxazol-6-yl)phenyl) ethanone was studied and the values of selected bond distances (?), bond angles (°), and dihedral angles (°) were found in agreement with the calculated (DFT, B3LYP/6-311++G(d,p)) values. Antimicrobial activity of these new compounds was also studied against a panel of microorganisms including Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Streptococcus mutans, and Candida albicans. Most of the dioxaborepines exhibited fair activities against these microorganisms. The pMIC values of the compounds were first correlated with Hammett polar substituent constant (σ) together with lipophilic constant (π) and statistically significant 2D correlations were obtained. In addition, the pMIC values of the compounds were correlated with some theoretical descriptors and fair 2D-QSAR models with clogP, SAA, and μ as independent variables were obtained.
- Pir, Meryem,Agirbas, Hikmet,Budak, Fatma,Sahin, Onur
-
-
Read Online
- Three-component synthesis and 1,3-dipolar cycloaddition of highly functionalized pyrans with nitrile oxides: Easy access to 1,2,4-oxadiazoles
-
Three-component reaction of 1-[(4-chlorophenyl)sulfanyl]acetone, malononitrile, and substituted aromatic aldehydes in the presence of sodium ethoxide under simple mixing at ambient temperature for 5-8 min afforded highly functionalized 4H-pyrans in good t
- Kumar, Raju Suresh,Ramar, Alagar,Perumal, Subbu,Almansour, Abdulrahman I.,Arumugam, Natarajan,Ali, Mohamed Ashraf
-
-
Read Online
- 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
-
-
Read Online
- 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
-
supporting information
p. 2431 - 2436
(2021/05/05)
-
- Site selective synthesis and anti-inflammatory evaluation of Spiro-isoxazoline stitched adducts of arteannuin B
-
A library of new spiroisoxazoline analogues of arteannuin B was synthesized through 1, 3-dipolar cycloaddition in stereoselective fashion and consequently screened for anti-inflammatory activity in RAW 264.7 macrophage cells. Three potent analogues (8i, 8 m, and 8n) were found to attenuate the LPS induced release of cytokines IL-6 and TNF-α more potently than the parent molecule. Also, the inhibition of LPS induced nitric oxide production in these cells show moderate to high efficacy. None of the three potent molecules have altered the viability of RAW 264.7 cells following 48 h incubation suggesting that the inhibition of cytokines and nitric oxide production exhibited in the cells was not due to toxicity. In addition, these compounds exhibit an IC50 range of 0.17 μM-1.57 μM and 0.09 μM-0.35 μM for the inhibition of IL-6 release and nitric oxide production respectively. The results disclose potent inhibition of pro-inflammatory mediators which are encouraging and warrant further investigations to develop new therapeutic agents for inflammatory diseases.
- Ur Rasool, Javeed,Sawhney, Gifty,Shaikh, Majeed,Nalli, Yedukondalu,Madishetti, Sreedhar,Ahmed, Zabeer,Ali, Asif
-
-
- 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
-
supporting information
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
-
-
- Synthesis and biological evaluation of novel isoxazole derivatives from acridone
-
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
-
-
- 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
-
-
- Electrochemical synthesis of 1,2,4-oxadiazoles from amidoximes through dehydrogenative cyclization
-
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
-
p. 10611 - 10616
(2021/12/27)
-
- A novel approach for the synthesis of functionalized hydroxylamino derivative of dihydroquinazolinones
-
A new metal-free and modular approach for the synthesis of various functionalized dihydroquinazolinones has been developed from isatoic anhydride, amines, 4-chloro-N-hydroxybenzimidoylchloride to yield up to 71%. The reaction has been screened in various bases, solvents at different temperatures. The substrate scope of the reaction has been studied with various amines and the possible reaction mechanism for this reaction has also been proposed.
- Jaganmohan, Chikkanti,Vinay Kumar,Venkateshwarlu,Mohanty, Sandeep,Kumar, Jaydeep,Venkateswara Rao,Raghunadh, Akula,Tadiparthi, Krishnaji
-
supporting information
p. 2163 - 2170
(2020/06/10)
-
- 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.
- -
-
Paragraph 0127; 0129
(2020/03/11)
-
- Study on the interaction of triaryl-dihydro-1,2,4-oxadiazoles with α-glucosidase
-
Purpose: One of the therapeutic approaches in the management of Type 2 diabetes is delaying the absorption of glucose through α-glucosidase enzymes inhibition, which can reduce the incidence of postprandial hyperglycemia. The existence of chronic postpran
- Khosravi, Arefeh,Vaezi, Gholamhassan,Hojati, Vida,Abdi, Khosrou
-
p. 109 - 117
(2020/01/11)
-
- 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
-
supporting information
p. 16626 - 16637
(2020/10/14)
-
- 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)
-
- Design, synthesis and evaluation of novel levoglucosenone derivatives as promising anticancer agents
-
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
-
-
- 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
-
-
- 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
-
-
- 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)
-
- 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.
-
-
- Palladium-Catalyzed Annulation of Aryltriazoles and Arylisoxazoles with Alkynes
-
We developed herein a palladium-catalyzed annulation of aryltriazoles and arylisoxazoles with internal alkynes via C?H bond activation process. 4,5-disubstituted-3H-naphtho[1,2-d][1,2,3]triazoles and 4,5-disubstituted-naphtho[2,1-d]isoxazoles could be afforded in good yields, respectively. The starting materials are readily available and the scope and applications of this transformation were explored. The reaction offers a practical approach to naphthalene fused heterocycles. (Figure presented.).
- Yuan, Hairui,Wang, Min,Xu, Zhenghu,Gao, Hongyin
-
supporting information
p. 4386 - 4392
(2019/08/12)
-
- Betulinic acid derivatives: a new class of α-glucosidase inhibitors and LPS-stimulated nitric oxide production inhibition on mouse macrophage RAW 264.7 cells
-
Chemical manipulation studies were conducted on betulinic acid (1), twenty-one new rationally designed analogues of 1 with modifications at C-28 were synthesized for their evaluation of inhibitory effects on α-glucosidase and LPS-stimulated nitric oxide production in mouse macrophage RAW 264.7 cells. Compound 2 (IC50 = 5.4 μM) exhibited an almost 1.4-fold increase in α-glucosidase inhibitory activity on yeast α-glucosidase while analogues 5 (IC50 16.4 μM) and 11 (IC50 16.6 μM) exhibited a 2-fold enhanced inhibitory activity on NO-production than betulinic acid.
- Gundoju, Narayanarao,Bokam, Ramesh,Yalavarthi, Nageswara Rao,Azad, Rajaram,Ponnapalli, Mangala Gowri
-
supporting information
p. 2618 - 2622
(2018/04/30)
-
- 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
-
supporting information
p. 7506 - 7510
(2019/11/28)
-
- Simple one-pot synthesis of 5-(chloromethyl)isoxazoles from aldoximes and 2,3-dichloro-1-propene
-
[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.
-
p. 1228 - 1232
(2020/01/08)
-
- Synthesis and biological activity of ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylate
-
A series of novel ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylates I-1-6 were synthesized. The structures of all target compounds were characterized by 1H NMR, 13C NMR, IR,MS and elemental analyses. Their fungicidal and herbicidal activities were evaluated. The results of preliminary bioassays show that the title compounds I-4 possess 20-50% inhibition against most of the tested plants at the dosage of 150 g ai/ha, while the title compounds I-1-5 possess 32-58% inhibition against FusaHum graminearum, Thanatephorus cucumeris, Botrytis cinereapers and Fusarium oxysporum in vitro at the concentration of 100 mg/L.
- Wang, Wei,Wang, Lie-Ping,Mao, Min-Zhen,Zhang, Xiao-Guang,Zheng, Xiao-Rui,Huang, Xiao-Ying,Xue, Chao,Ning, Bin-Ke
-
p. 164 - 167
(2017/11/20)
-
- 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
-
supporting information
p. 2018 - 2020
(2018/04/25)
-
- 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
-
supporting information
p. 1990 - 1995
(2017/06/09)
-
- 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)
-
- The hydrogen bond directing effect in nitrile oxide cycloadditions to allylic substituted cyclopentenes
-
A quantitative evaluation of the H-bond directing effect on the stereoselectivity in the cycloaddition of nitrile oxides to 2-cyclopenten-1-ol and allylic cyclopentenyl amides is reported. In apolar solvents the H-bond directing effect promotes a high syn stereoselectivity while H-bond acceptor solvents divert the reactions to the anti face of the dipolarophile. Taft's β parameter gives a good description of the solvent effect on the H-bond directing effect. The persistence of some syn stereoselectivity even in good H-bond acceptor solvents points out the existence of some residual hydrogen bond direction. The syn stereoselectivity in the presence of M(II) salts was also investigated and the results discussed in the light of the potential application of these scaffolds in nucleoside synthesis.
- Cardarelli, Anna Maria,Fassardi, Vera,Memeo, Misal Giuseppe,Quadrelli, Paolo
-
p. 2602 - 2613
(2017/04/10)
-
- 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
-
supporting information
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.
- -
-
Paragraph 0188
(2017/06/28)
-
- 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)
-
- A field-based disparity analysis of new 1,2,5-oxadiazole derivatives endowed with antiproliferative activity
-
A series of 1,2,5-oxadiazoles were synthesized as new potential antiproliferative agents. The in vitro cytotoxic activity evaluation of title compounds through MTT assay revealed that some of them showed significant activity against the HCT-116 cancer cell line. The field-based disparity analysis provided indications about the electrostatic, hydrophobic, and shape features underlying the cytotoxicity, suggesting that increasing the negative electrostatic field on the heterocyclic core of the structure has positive effects on the activity. The structure–activity relationships (SAR) around a particular compound can be explained allowing for a structural rationale for the differences in activity. The SAR provided by this series of compounds can be exploited to carry out further lead optimization.
- Porta, Federica,Gelain, Arianna,Barlocco, Daniela,Ferri, Nicola,Marchianò, Silvia,Cappello, Valentina,Basile, Livia,Guccione, Salvatore,Meneghetti, Fiorella,Villa, Stefania
-
p. 820 - 839
(2017/10/03)
-
- Design, synthesis and SAR of a novel series of heterocyclic phenylpropanoic acids as GPR120 agonists
-
A novel series of 5-membered heterocycle-containing phenylpropanoic acid derivatives was discovered as potent GPR120 agonists with low clearance, high oral bioavailability and in vivo antidiabetic activity in rodents.
- Zhang, Xuqing,Cai, Chaozhong,Winters, Michael,Wells, Michele,Wall, Mark,Lanter, James,Sui, Zhihua,Ma, Jingyuan,Novack, Aaron,Nashashibi, Imad,Wang, Yuanping,Yan, Wen,Suckow, Arthur,Hua, Hong,Bell, Austin,Haug, Peter,Clapper, Wilma,Jenkinson, Celia,Gunnet, Joseph,Leonard, James,Murray, William V.
-
p. 3272 - 3278
(2017/07/07)
-
- POLYCYCLIC PYRAZOLINONE DERIVATIVE AND HERBICIDE COMPRISING SAME AS EFFECTIVE COMPONENT THEREOF
-
Provided are a polycyclic pyrazolinone derivative indicated by general formula (1) (in the formula, R1, X1, X2, X3, and Y indicate the definitions provided in the Specification) and a herbicide comprising same as effective component thereof.
- -
-
Paragraph 0941; 0943
(2016/02/19)
-
- Synthesis, molecular docking study, and cytotoxic activity of 3,4-diaryl-5-(4-pyridinyl)-1,2,4-oxadiazole
-
Background: Triaryl oxadiazoles have been proven to be useful agents against various types of cancer cell lines. Nevertheless, their mechanism of action is not fully understood. Objective: Synthesis and cytotoxic activity of a new group of triaryl oxadiaz
- Zareian, Bita,Ghadbeighi, Sajad,Amirhamzeh, Amirali,Ostad, Seyed N.,Shafiee, Abbas,Amini, Mohsen
-
p. 394 - 401
(2016/07/06)
-
- 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)
-
- 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)
-
- Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles
-
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
-
supporting information
p. 3997 - 4001
(2016/03/19)
-
- Synthesis, characterization, antimicrobial activity, and QSAR studies on substituted oxadiazaboroles
-
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
-
p. 1794 - 1812
(2016/10/03)
-
- 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)
-
- Synthesis of new dithiolethione and methanethiosulfonate systems endowed with pharmaceutical interest
-
Here we report synthetic methodology affording in the most efficient way the rapid preparation of new dithiolethiones (DTTs) and methanethiosulfonates (MTSs). These were evaluated as STAT3 inhibitors since these electrophilic systems could react with thio
- Gabriele, Elena,Porta, Federica,Facchetti, Giorgio,Galli, Corinna,Gelain, Arianna,Meneghetti, Fiorella,Rimoldi, Isabella,Romeo, Sergio,Villa, Stefania,Ricci, Chiara,Ferri, Nicola,Asai, Akira,Barlocco, Daniela,Sparatore, Anna
-
p. 235 - 250
(2017/03/09)
-
- 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)
-
- Five-membered azole heterocyclic compound and its preparation method, pharmaceutical composition and use thereof
-
The present invention relates to a five-membered azole heterocycle compound represented by the following general formula (I), a preparation method of the five-membered azole heterocycle compound, a drug composition of the five-membered azole heterocycle compound, and a use of the five-membered azole heterocycle compound in preparation of drugs for prevention or treatment of TGR5-mediated diseases. The formula (I) is represented by the instruction.
- -
-
Paragraph 0237; 0238; 0252; 0253
(2017/02/28)
-
- 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)
-