2289-55-6Relevant academic research and scientific papers
Synthesis of Isoxazole- And Oxazole-4-carboxylic Acids Derivatives by Controlled Isoxazole-Azirine-Isoxazole/Oxazole Isomerization
Serebryannikova, Anna V.,Galenko, Ekaterina E.,Novikov, Mikhail S.,Khlebnikov, Alexander F.
, p. 15567 - 15577 (2019/11/16)
The first synthesis of isoxazole-4-carboxylic acid derivatives by domino isoxazole-isoxazole isomerization is reported. Fe(II)-catalyzed isomerization of 4-acyl-5-methoxy-/5-aminoisoxazoles (dioxane, 105 °C) leads to the formation of isoxazole-4-carboxylic esters and amides in good yields. 4-Formyl-5-methoxyisoxazoles give methyl oxazole-4-carboxylates under the same reaction conditions. Fe(II)-catalyzed isomerization of 4-acyl-5-methoxyisoxazoles under milder conditions (MeCN, 50 °C) allows the preparation of transient 2-acyl-2-(methoxycarbonyl)-2H-azirines. The azirines isomerize quantitatively either into isoxazoles under catalytic conditions (dioxane, 105 °C) or into oxazoles under noncatalytic thermolysis (o-dichlorobenzene, 170 °C). The mechanism of the isomerization and dependence of the reaction routes on substituents at starting isoxazole core and reaction conditions are discussed on the basis of DFT calculations.
Synthesis, pharmacological characterization, and docking analysis of a novel family of diarylisoxazoles as highly selective cyclooxygenase-1 (COX-1) inhibitors
Vitale, Paola,Tacconelli, Stefania,Perrone, Maria Grazia,Malerba, Paola,Simone, Laura,Scilimati, Antonio,Lavecchia, Antonio,Dovizio, Melania,Marcantoni, Emanuela,Bruno, Annalisa,Patrignani, Paola
, p. 4277 - 4299 (2013/07/19)
3-(5-Chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6), a known selective cyclooxygenase-1 (COX-1) inhibitor, was used to design a new series of 3,4-diarylisoxazoles in order to improve its biochemical COX-1 selectivity and antiplatelet efficacy. Structure-activity relationships were studied using human whole blood assays for COX-1 and COX-2 inhibition in vitro, and results showed that the simultaneous presence of 5-methyl (or -CF3), 4-phenyl, and 5-chloro(-bromo or -methyl)furan-2-yl groups on the isoxazole core was essential for their selectivity toward COX-1. 3g, 3s, 3d were potent and selective COX-1 inhibitors that affected platelet aggregation in vitro through the inhibition of COX-1-dependent thromboxane (TX) A2. Moreover, we characterized their kinetics of COX-1 inhibition. 3g, 3s, and 3d were more potent inhibitors of platelet COX-1 and aggregation than P6 (named 6) for their tighter binding to the enzyme. The pharmacological results were supported by docking simulations. The oral administration of 3d to mice translated into preferential inhibition of platelet-derived TXA2 over protective vascular-derived prostacyclin (PGI2).
Functionalized diarylisoxazoles inhibitors of ciclooxygenase
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Page/Page column 13, (2009/07/25)
The present invention refers to isoxazole derivatives, in particular diarylisoxazole derivatives inhibitors of cyclooxygenase (COX), in particular cyclooxygenase-1 (COX-1), to their pharmaceutical compositions, the process for their preparation and their use for the chemoprevention and treatment of inflammatory syndromes and in the prevention and treatment of carcinomas, in particular intestinal, ovarian and cutaneous carcinomas, in the treatment of pain syndromes, in particular after surgery, and in the cardiovascular field as antithrombotics/vasoprotectives/cardioprotectives.
Transformation of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole derivatives into isoxazoles
Chukanov,Popov,Romanenko,Reznikova
, p. 1227 - 1233 (2008/09/19)
The reactions of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole derivatives with electrophilic reagents, such as protic acids, benzoyl chloride, BF 3, and bromine, produce isoxazole, 2,2,3,3-tetramethylaziridine, and 2,3,3-trimethylpropen-2-ylamine
The synthesis of highly substituted isoxazoles by electrophilic cyclization: An efficient synthesis of valdecoxib
Waldo, Jesse P.,Larock, Richard C.
, p. 9643 - 9647 (2008/03/17)
(Chemical Equation Presented) A large number of functionally substituted 2-alkyn-1-one O-methyl oximes have been cyclized under mild reaction conditions in the presence of ICl to give the corresponding 4-iodoisoxazoles in moderate to excellent yields. The resulting 4-iodoisoxazoles undergo various palladium-catalyzed reactions to yield 3,4,5-trisubstituted isoxazoles, including valdecoxib.
Preparation of Oxazoline N-Oxides and Imidate N-Oxides by Amide Acetal Condensation and Their Cycloaddition Reactions
Ashburn, Stephen P.,Coates, Robert M.
, p. 3076 - 3081 (2007/10/02)
2,4,4-Trimethyloxazoline N-oxide (3a), 4,4-dimethyl-2-phenyloxazoline N-oxide (3b), and ethyl N-methylbenzimidate N-oxide (4) have been prepared by condensation of 2-(hydroxyamino)-2-methyl-1-propanol hydrochloride (1) with acetamide or benzamide acetals
Regioselectivity in cycloaddition reactions on solid phases
Yedidia, Varda,Leznoff, Clifford C.
, p. 1144 - 1150 (2007/10/02)
A 1percent crosslinked divinylbenzene-styrene copolymer, incorporating benzyl acrylate groups, reacted in normal Diels-Alder reactions with E-1-phenyl-1,3-butadiene or methyl E-2,4-pentadienoate to give their respective polymer-bound benzyl cyclohexenecarboxylates.Polymer-bound benzyl propiolate and polymer-bound benzyl phenylpropiolate reacted with benzonitrile oxide in a typical 1,3-dipolar addition reaction to give their respective polymer-bound isoxazoles.Cleavage of the polymer-bound Diels-Alder adducts and the polymer-bound 1,3-dipolar addition adduct derived from polymer-bound benzyl propiolate gave mixtures of ortho and meta regiomers similar to those produced in analogous reactions in solution.Cleavage of the polymer-bound 1,3-dipolar addition adduct, derived from polymer-bound benzyl phenylpropiolate, followed by esterification, gave a solitary adduct, 4-carbomethoxy-3,5-diphenylisoxazole, but an analogous solution 1,3-dipolar addition yielded a 1:1 ratio of the two possible regiomers.
