1143-82-4Relevant academic research and scientific papers
A New Series of 1,3,4-Oxadiazole Linked Quinolinyl-Pyrazole/Isoxazole Derivatives: Synthesis and Biological Activity Evaluation
Basavanna, V.,Bhadraiah, U. K.,Chandra,Chandramouli, M.,Doddamani, Shridevi,Kempaiah, C.,Lingegowda, N. S.,Ningaiah, S.
, p. 2257 - 2266 (2021/12/23)
Abstract: A series of 1,3,4-oxadiazole bridged pyrazole/isoxazole bearing quinoline derivatives has been designed and synthesized by a clean and convenient method. Structures of the newly synthesized compounds have been confirmed by FTIR, 1H and 13C NMR, and HRMS spectral data. The titled compounds have been evaluated for their molecular docking guided antimicrobial and anti-inflammatory activity. One of 1,3,4-oxadiazole bridged quinolinyl-pyrazole derivatives has interacted efficiently with E. Coli protein (PDB file: 1KZN), and has been characterized by good antimicrobial activity against the majority of the tested pathogens. Another product has exhibited excellent anti-inflammatory activity.
Design, synthesis and in vitro biological evaluation of isoxazol-4-carboxa piperidyl derivatives as new anti-influenza A agents targeting virus nucleoprotein
Pei, Shuchen,Xia, Shihao,Yang, Fating,Chen, Junlin,Wang, Mengdie,Sun, Wanlin,Li, Ziqiang,Yuan, Kangyao,Chen, Jun
, p. 4446 - 4454 (2020/02/13)
Influenza infection is a major cause of morbidity and mortality during seasonal epidemics and sporadic pandemics. It is important and urgent to develop new anti-influenza agents with a new mechanism of action. Nucleozin has been reported as a potent antagonist of nucleoprotein accumulation in the nucleus. In this study, a new series of isoxazol-4-carboxa piperidyl derivatives 1a-j were synthesized and their chemical structures were confirmed by 1H, 13C NMR and mass spectral data. Furthermore, all the synthesized compounds were evaluated for in vitro anti-influenza virus activity against influenza virus (A/PR/8/34 H1N1). Among all the compounds, 1a, 1b, 1c, 1f and 1g exhibited more potent activity than the standard drug, and compound 1b has showed most promising anti-influenza virus activity. These results are also consistent with the docking study results in terms of the design of compounds targeting influenza A via viral nucleoprotein.
Hypervalent Iodine(III) Reagent Mediated Regioselective Cycloaddition of Aldoximes with Enaminones
Yoshimura, Akira,Jarvi, Melissa E.,Shea, Michael T.,Makitalo, Cody L.,Rohde, Gregory T.,Yusubov, Mekhman S.,Saito, Akio,Zhdankin, Viktor V.
, p. 6682 - 6689 (2019/11/02)
An efficient oxidative cycloaddition of enaminones with nitrile oxides generated in situ from respective aldoximes using hypervalent iodine reagents has been developed. Reactions of various aldoximes with enaminones in the presence of [hydroxy(tosyloxy)iodo]benzene involved the regioselective cycloaddition reaction resulting in the formation of the 3,4-disubstituted isoxazoles in moderate to good yields. Structures of several isoxazole products were confirmed by a single X-ray crystallography.
Stem cells are the most sensitive screening tool to identify toxicity of GATA4-targeted novel small-molecule compounds
Karhu, S. Tuuli,V?lim?ki, Mika J.,Jumppanen, Mikael,Kinnunen, Sini M.,Pohjolainen, Lotta,Leigh, Robert S.,Auno, Samuli,F?ldes, Gábor,Boije af Genn?s, Gustav,Yli-Kauhaluoma, Jari,Ruskoaho, Heikki,Talman, Virpi
, p. 2897 - 2911 (2018/07/15)
Safety assessment of drug candidates in numerous in vitro and experimental animal models is expensive, time consuming and animal intensive. More thorough toxicity profiling already in the early drug discovery projects using human cell models, which more closely resemble the physiological cell types, would help to decrease drug development costs. In this study we aimed to compare different cardiac and stem cell models for in vitro toxicity testing and to elucidate structure–toxicity relationships of novel compounds targeting the cardiac transcription factor GATA4. By screening the effects of eight compounds at concentrations ranging from 10?nM up to 30?μM on the viability of eight different cell types, we identified significant cell type- and structure-dependent toxicity profiles. We further characterized two compounds in more detail using high-content analysis. The results highlight the importance of cell type selection for toxicity screening and indicate that stem cells represent the most sensitive screening model, which can detect toxicity that may otherwise remain unnoticed. Furthermore, our structure–toxicity analysis reveals a characteristic dihedral angle in the GATA4-targeted compounds that causes stem cell toxicity and thus helps to direct further drug development efforts towards non-toxic derivatives.
Chiral Mercaptoacetamides Display Enantioselective Inhibition of Histone Deacetylase6 and Exhibit Neuroprotection in Cortical Neuron Models of Oxidative Stress
Kalin, Jay H.,Zhang, Hankun,Gaudrel-Grosay, Sophie,Vistoli, Giulio,Kozikowski, Alan P.
experimental part, p. 425 - 439 (2012/06/04)
Mercaptoacetamide-based ligands have been designed as a new class of histone deacetylase (HDAC) inhibitors for possible use in the treatment of neurodegenerative diseases. The thiol group of these compounds provides a key binding element for interaction with the catalytic zinc ion, and thus differs from the more typically employed hydroxamic acid based zinc binding groups. Herein we disclose the chemistry and biology of some substituted mercaptoacetamides with the intention of increasing HDAC6 isoform selectivity while maintaining potency similar to their hydroxamic acid analogues. The introduction of a stereocenter α to the thiol group was found to have a considerable impact on HDAC inhibitor potency. These new compounds were also profiled for their therapeutic potential in an invitro model of stress-induced neuronal injury and were found to act as nontoxic neuroprotective agents.
Isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists
Nakamura, Masayuki,Kurihara, Hideki,Suzuki, Gentaroh,Mitsuya, Morihiro,Ohkubo, Mitsuru,Ohta, Hisashi
scheme or table, p. 726 - 729 (2010/05/18)
This Letter describes the synthesis and evaluation of mGluR7 antagonists in the isoxazolopyridone series. In the course of modification in this class, novel solid support synthesis of the isoxazolopyridone scaffold was developed. Subsequent chemical modification led to the identification of several potent derivatives with improved physicochemical properties compared to a hit compound 1. Among these, 2 showed good oral bioavailability and brain penetrability, suggesting that 2 may be useful for in vivo study to elucidate the role of mGluR7.
PROCESS FOR PREPARING ISOXAZOLE COMPOUNDS
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Page/Page column 2, (2010/03/31)
A process for preparing isoxazole compounds of formula I: in which a nitroaryl of the formula (II): is contacted with an alkyl acetoacetate of the formula (III) or a salt thereof: in the presence of an activating agent and a base to provide the isoxazole compound.
A convenient synthesis of functionalized isoxazolines and related 5-hydroxyisoxazolidine-4-carboxylates
Benfatti, Fides,Cardillo, Giuliana,Contaldi, Simone,Gentilucci, Luca,Mosconi, Elisa,Tolomelli, Alessandra,Juaristi, Eusebio,Reyes-Rangel, Gloria
body text, p. 2478 - 2483 (2009/08/07)
The effectiveness of Sc(OTf)3 as a Lewis acid catalyst for the 1,4-addition reaction of carbamates to appropriate 2-acetyl-2-pentenoic esters is herein reported. In particular, N-benzyl-(tert-butyldimethylsilyloxy)carbamate added efficiently to
ISOXAZOLOPYRIDINE DERIVATIVES FOR USE IN THE TREATMENT OF HIF-MEDIATED CONDITIONS
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Page/Page column 65, (2009/07/17)
The present invention relates to novel compounds of formula (I) capable of modulating the stability and/or activity of hypoxia inducible factor (HIF) by inhibiting the activity of at least one HIF hydroxylase enzyme.
Formation of α-hydroxy-β-diketones through hydroxylation of isoxazolium salts: Stereoselective approach to angular cis-diols in polycyclic systems
Takikawa, Hiroshi,Takada, Akiomi,Hikita, Katsuyoshi,Suzuki, Keisuke
supporting information; experimental part, p. 7446 - 7449 (2009/03/12)
Only two steps were needed for the unprecedented oxidation of isoxazoles, which is exploited in the stereocontrolled introduction of an "angular cis-diol" characteristic of polyketide-derived polycyclic natural products, suchas 3. In this two-step process, 1) N-methylation of isoxazole 1 and 2) stereoselective epoxidation of isoxazolium salt 2 withsodium hypochlorite followed by hydrolysis are carried out (Bn: benzyl). (Chemical Equation Presented)
