Advances in clinical and experimental medicine : official organ Wroclaw Medical University 2012-01-01

The synthesis of 3,5,6,7-tetrasubstituted isoxazolo[4,5-b]pyridines and an evaluation of their in vitro antiproliferative activity.

Krystyna Poreba, Joanna Wietrzyk

Index: Adv. Clin. Exp. Med. 21(5) , 563-71, (2012)

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Abstract

Derivatives of isoxazolopyridines exhibit diverse biological activity. One method of synthesizing isoxazolo[4,5-b]pyridines is Friedlander condensation.To establish the conditions necessary for conventional and microwave synthesis of new 3,5,6,7-tetrasubstituted isoxazolo[4,5-b]pyridines and their antiproliferative activity.The substrates in the synthesis of new isoxazolo[4,5-b]pyridines were 4-amino-5-benzoylisoxazole-3-carboxamide and selected carbonyl compounds containing a reactive a-methylene group. Reactions were carried out using classical methods in the presence of catalysts ZnCl2 or In (OTf)3, and in a microwave reactor in the presence of ZnCl2 under solvent-free conditions. Selected compounds were tested in vitro on eight tumor cell lines to assess their antiproliferative activity.A series of new derivatives of 3,5,6,7-tetrasubstituted isoxazolo [4,5-b]pyridines was obtained from Friedlander condensation of 4-amino-5-benzoyloisoxazolo-3-carboxamide with selected carbonyl compounds with an active methylene group. The compounds were obtained by conventional and microwave methods, in the presence of catalysts ZnCl2 or In (OTf)3. The structures of the products were determined on the basis of elemental analysis and infrared (IR), Nuclear Magnetic Resonance (1H NMR) and Mass Spectrometry (MS) data. Selected compounds were tested in vitro on eight tumor cell lines in the direction of antiproliferative activity.Only the use of conventional heating in a thermostated oil bath in the presence of catalysts ZnCl2, or In (OTF)3 or microwave irradiation in the presence ZnCl2 in the solvent-free conditions allowed good yields of the new derivatives of poly-substituted isoxazolo[4,5-b]pyridines to be obtained. Among the compounds tested in vitro only 6-benzoyl-5, 7-difenyloisoxazolo[4,5-b]pyridine showed antyproliferative activity at a concentration of 3.9 microg/ml.