A series of novel 3-(coumarin-4-yl)tetrahydroisoxazoles 5a,b, 7, 9 and 3-(coumarin-4-yl)dihydropyrazoles 13a-d, 14, 15a,b were synthesized from coumarin-4-carboxaldehyde 1 via the intermediate N-methyl nitrone 3 and N-phenyl or N-methyl hydrazones 11a,b. These coumarin derivatives were isolated, characterized and evaluated in vitro for their ability to inhibit trypsin, β-glucuronidase, soybean lipoxygenase and to interact with the stable radical 1,1-diphenyl-2-picrylhydrazyl. The compounds were tested in vivo as antiinflammatory agents in the rat carrageenin paw edema assay. Compound 15a seems to be a lead molecule to be modified in order to improve the lipoxygenase inhibition. The results are discussed in terms of structural characteristics.J. Heterocyclic Chem., 38, 717 (2001).Coumarins have been reported to have multiple biological activities [1]. It is to be expected that coumarins might affect the formation and scavenging of reactive substances derived from oxygen (Reactive Oxygen Species, ROS) and influence processes involving free radical-mediated injury, as can some other plant phenolics and flavonoids [2,3]. There is evidence that the naturally occuring prototypical compound, coumarin can reduce tissue oedema and inflammation [4]. Coumarin and 7-hydroxycoumarin inhibit prostaglandin biosynthesis, which involves fatty acid hydroperoxy intermediates [5]. Various coumarin related derivatives are recognised as inhibitors not only of the lipoxygenase and cyclooxygenase pathways of arachidonate metabolism [6,7,8], but also of neutrophile dependent superoxide anion generation [9].In connection to our previous work on the synthesis of coumarin derivatives [10][11][12][13][14] In continuation to these studies we tried to design and synthesize novel coumarins like the new 4-(3'-tetrahydroisoxazolyl)-and 4-(3'-dihydropyrazolyl)coumarin derivatives and to define structure features for active compounds and to discuss our results in terms of structure-activity relationships. The reactions studied and the products (new compounds) obtained are depicted in schemes 1-2.We prepared previously 4-(3'-isoxazolinyl)coumarins through 1,3-cycloaddition reactions of 2-oxo-2H-[1]benzopyran-4-carbonitrile N-oxide with different dipolarophiles [16]. In this work we try to extend those 1,3-cycloaddition reactions by preparing the new dipoles 3 and 12a,b and studying their reactions with dipolarophiles 4a,b, 6, 8.Treatment of ethanol solution of aldehyde 1 with Nmethyl hydroxylamine hydrochloride 2 and sodium acetate under reflux (Scheme 1) gave as a precipitate, after ice/water work up, the new nitrone 3 (54% yield). Reactions of compound 3 with maleimides 4a,b resulted to new isoxazolidines 5a (47%), 5b (83%) respectively as the sole 1,3-cycloadducts. The chemical shifts for 5-H (5.02, d, J = 7.6 Hz), 3-H (4.82, d, J = 2.5 Hz), 4-H (3.94, dd, J 1 = 2.5 Hz, J 2 = 7.6 Hz) of 5a and 5-H (4.92, d, J = 7.4 Hz), 3-H (4.66, d, J = 2.7 Hz), 4-H (3.79, dd, J 1 = 2.7 Hz, J = 7.4 Hz) of 5b resemble well with the proposed structures in analogy...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.