698-16-8Relevant academic research and scientific papers
Highly regioselective dipolar cycloadditions of nitrile oxides with α,β-acetylenic aldehydes
Jiang, Longqiang,Gao, Tao,Li, Zhi,Sun, Shaofa,Kim, Claudia,Huang, Changfeng,Guo, Haibing,Wang, Jian,Xing, Yalan
, p. 712 - 714 (2016)
1,2-Oxazol derivatives 3 were prepared by a highly regioselective 1,3-dipolar cycloaddition of nitrile oxides and α,β-acetylenicaldehydes 1 in good yields. Reactive nitrile oxides were generated in situ from stable chloro-oxime reagents 2 and triethyl ami
Synthesis and substituent effect study on 13C NMR chemical shifts of 4-(substitue-phenyl)-6-methyl-3-phenyl-4H-1,2,4-oxadiazin-5(6H)-one
Kara, Yesim S.,Y?ld?z, Berna
, (2021/11/16)
The twelve novel 4-(substituted-phenyl)-6-methyl-3-phenyl-4H-1,2,4-oxadiazin-5(6H)-one derivatives were synthesized by the reactions of N-Substituted-phenyl-benzamide oximes with 2-bromopropionyl chloride. The synthesized 1,2,4-oxadiazin-5-one derivatives
Ru-Catalyzed [3 + 2] Cycloaddition of Nitrile Oxides and Electron-Rich Alkynes with Reversed Regioselectivity
Feng, Qiang,Huang, Hai,Sun, Jianwei
supporting information, p. 2431 - 2436 (2021/05/05)
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
Design and synthesis of sinomenine isoxazole derivatives via 1,3-dipolar cycloaddition reaction
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)
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.
Synthesis and biological evaluation of novel isoxazole derivatives from acridone
Aarjane, Mohammed,Slassi, Siham,Tazi, Bouchra,Amine, Amina
, (2020/12/07)
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.
Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
Umm-E-Farwa,Ullah, Saeed,Khan, Maria Aqeel,Zafar, Humaira,Atia-tul-Wahab,Younus, Munisaa,Choudhary, M. Iqbal,Basha, Fatima Z.
, (2021/05/10)
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.
Novel selective ido1 inhibitors with isoxazolo[5,4-d]pyrimidin-4(5h)-one scaffold
?vajger, Urban,Bratkovi?, Toma?,Dol?ak, Ana,Gobec, Stanislav,Mlinari?, Larisa,Ogorevc, Eva,Sova, Matej
, (2021/04/02)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising target in immunomodulation of several pathological conditions, especially cancers. Here we present the synthesis of a series of IDO1 inhibitors with the novel isoxazolo[5,4-d]pyrimidin-4(5H)-one scaffold. A focused library was prepared using a 6-or 7-step synthetic procedure to allow a systematic investigation of the structure-activity relationships of the described scaffold. Chemistry-driven modifications lead us to the discovery of our best-in-class inhibitors possessing p-trifluoromethyl (23), p-cyclohexyl (32), or p-methoxycarbonyl (20, 39) substituted aniline moieties with IC50 values in the low micromolar range. In addition to hIDO1, compounds were tested for their inhibition of indoleamine 2,3-dioxygenase 2 and tryptophan dioxygenase, and found to be selective for hIDO1. Our results thus demon-strate a successful study on IDO1-selective isoxazolo[5,4-d]pyrimidin-4(5H)-one inhibitors, defining promising chemical probes with a novel scaffold for further development of potent small-molecule immunomodulators.
Site selective synthesis and anti-inflammatory evaluation of Spiro-isoxazoline stitched adducts of arteannuin B
Ur Rasool, Javeed,Sawhney, Gifty,Shaikh, Majeed,Nalli, Yedukondalu,Madishetti, Sreedhar,Ahmed, Zabeer,Ali, Asif
, (2021/10/16)
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.
Design, synthesis, and biological evaluation of N-(4-substituted)-3-phenylisoxazolo[5,4–d]pyrimidin-4-amine derivatives as apoptosis-inducing cytotoxic agents
Bansod, Sapana,Gaikwad, Nikhil Baliram,Garise, Ramana,Godugu, Chandraiah,Mara, Alekhya,Srinivas, Nanduri,Yaddanapudi, Venkata Madhavi
, (2021/08/05)
A library of new 3-phenylisoxazolo[5,4–d]pyrimidines (8–10) was designed based on a scaffold hybridization technique incorporating the important pharmacophoric features of 4-aminopyrimidine and phenyl isoxazole scaffold which is renowned for its BET inhib
Construction of spiro-1,2,4-oxadiazoline-fused matrine-type alkaloids as pesticidal agents
Lv, Min,Ma, Qianjun,Xu, Hui,Zhang, Shaoyong
, (2021/09/16)
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
