49660-38-0Relevant articles and documents
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.
Design, synthesis, and evaluation of hydroxamic acid derivatives as promising agents for the management of Chagas disease
Rodrigues, Giseli Capaci,Feijó, Daniel Ferreira,Bozza, Marcelo Torres,Pan, Peiwen,Vullo, Daniela,Parkkila, Seppo,Supuran, Claudiu T.,Capasso, Clemente,Aguiar, Alcino Palermo,Vermelho, Alane Beatriz
, p. 298 - 308 (2014/02/14)
Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5-dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g) was evaluated in detail and shows promising features as an antitrypanosomal agent. Excellent values for the inhibition of growth for all three developmental forms of the parasite were observed at low concentrations of 5g (IC50 values from 7.0 to 1 μM). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream parasites and that all treated mice survived; it was also more effective than the standard drug benznidazole.
One-pot synthesis of isoxazolines from aldehydes catalyzed by iodobenzene
Han, Liuquan,Zhang, Bijun,Xiang, Changbin,Yan, Jie
, p. 503 - 509 (2014/03/21)
A convenient one-pot, three-step procedure for the synthesis of isoxazolines starting from aldehydes has been developed involving catalytic cycloaddition between nitrile oxides and alkenes, in which iodobenzene is used as the catalyst for the in situ generation of a hypervalent iodine intermediate. In this approach, the aldehydes are first transformed with hydroxylamine sulfate into aldoximes, which are then oxidized to nitrile oxides by the in situ generated hypervalent iodine intermediate; finally, a 1,3-dipolar cycloaddition between the nitrile oxides and alkenes occurs to provide the isoxazolines in moderate to good yields.
Design and synthesis of potent, isoxazole-containing renin inhibitors
Fournier, Pierre-André,Arbour, Mélissa,Cauchon, Elizabeth,Chen, Austin,Chefson, Amandine,Ducharme, Yves,Falgueyret, Jean-Pierre,Gagné, Sébastien,Grimm, Erich,Han, Yongxin,Houle, Robert,Lacombe, Patrick,Lévesque, Jean-Franois,MacDonald, Dwight,MacKay, Bruce,McKay, Dan,Percival, M. David,Ramtohul, Yeeman,St-Jacques, René,Toulmond, Sylvie
scheme or table, p. 2670 - 2674 (2012/05/31)
The design and optimization of a novel isoxazole S1 linker for renin inhibitor is described herein. This effort culminated in the identification of compound 18, an orally bioavailable, sub-nanomolar renin inhibitor even in the presence of human plasma. When compound 18 was found to inhibit CYP3A4 in a time dependent manner, two strategies were pursued that successfully delivered equipotent compounds with minimal TDI potential.
Design and synthesis of spiro derivatives of parthenin as novel anti-cancer agents
Reddy, Doma Mahendhar,Qazi, Naveed A.,Sawant, Sanghpal D.,Bandey, Abid H.,Srinivas, Jada,Shankar, Mannepalli,Singh, Shashank K.,Verma, Monika,Chashoo, Gousia,Saxena, Arpita,Mondhe, Dilip,Saxena, Ajit K.,Sethi,Taneja, Subhash C.,Qazi, Gulam N.,Sampath Kumar
body text, p. 3210 - 3217 (2011/07/31)
Several novel spiro derivatives of parthenin (1) have been synthesized by the dipolar cycloaddition using various dipoles viz; benzonitrile oxides, nitrones and azides with exocyclic double bond of C ring (α-methylene- γ-butyrolactone). Majority of the compounds exhibited improved anti-cancer activity compared to the parthenin, when screened for their in vitro cytotoxicity against three human cancer cell lines viz., SW-620, DU-145 and PC-3. In vivo screening of select analog revealed improved anti-cancer activity with low mammalian toxicity as compared to parthenin. The results of the cytotoxicity pattern of these derivatives reveals the SAR of these sesquiterpinoid lactones and possible role of α,β-unsaturated ketone of parthenin in inhibiting NF-kB. A mechanistic correlation of anti-cancer activity along with in vivo and western blotting experiments has been described.
Regioselective synthesis and side-chain metallation and elaboration of 3-aryl-5-alkylisoxazoles
Di Nunno, Leonardo,Scilimati, Antonio,Vitale, Paola
, p. 2659 - 2665 (2007/10/03)
A number of 3-aryl-5-alkylisoxazoles have been synthesized in high yields by reacting arylnitrile oxides with free enolate ions regioselectively obtained by metallation of various alkyl methyl ketones with LDA in THF at -78°C followed by dehydration. Inve
SYNTHESIS OF 3-ARYL-4,5-DIHYDRO-5-HYDROXY-1,2-OXAZOLES BY REACTION OF SUBSTITUTED BENZONITRILE OXIDES WITH THE ENOLATE ION OF ACETALDEHYDE.
Di Nunno, L.,Scilimati, A.
, p. 2181 - 2190 (2007/10/02)
By reaction of substituted benzonitrile oxides with the enolate ion of acetaldehyde (quantitatively generated by the known cycloreversion of THF in the presence of n-butyllithium) a number of 3-aryl-4,5-dihydro-5-hydroxy-1,2-oxazoles (previously unknown or, in two cases, only synthesized by different procedures) have been isolated in high yields.Treatment of such hydroxy-isoxalines with some common bases allows their conversion in high yields into the corresponding isoxazoles.
STEREOCHEMISTRY OF IMINOXY RADICALS
Alberti, Angelo,Barbaro, Gaetano,Battaglia, Arturo,Guerra, Maurizio,Bernardi, Fernando,et al.
, p. 742 - 750 (2007/10/02)
Iminoxy radicals of general structure Ar-C(X)=N-O, where X=H, CH2OH, n-Bu, t-Bu, SiEt3, SiPh3, GePh3, SnMe3, SnBu3, SnPh3, SMe, SBu, SPh, Cl and Br, have been photolytically generated from the parent oximino compounds or from aromatic nitrile N-oxides in an aprotic solvent.Two configurational isomers, interconvertible in solution, have been detected by electron spin resonance spectroscopy for the majority of these radicals.The preferred geometry of iminoxyls derived from ortho-unsubstituted benzaldoximes is that which places the aryl ring and the oxygen atom on the same side of the C=N double bond (anti).Substitution of the azomethine proton leads to a stabilization of the syn configuration, the effect being larger the greater the atomic number of the leading atom of the substituent group.The relative stability of the syn isomer is also increased by substitution of the aromatic ortho protons.INDO calculations have been carried out on several model systems in order to rationalize the experimental results.The effects responsible for the configurational preference of the different terms of this series of radicals are discussed in terms of a perturbation molecular orbital (PMO) approach.
