Department of Drug Technology, Wroclaw Medical University, Wroclaw, Poland.
Adv Clin Exp Med. 2012 Sep-Oct;21(5):563-71.
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.
异噁唑并吡啶衍生物表现出多种生物活性。合成异噁唑并[4,5-b]吡啶的一种方法是 Friedlander 缩合。
建立常规和微波合成新型 3,5,6,7-四取代异噁唑并[4,5-b]吡啶及其抗增殖活性的条件。
新异噁唑并[4,5-b]吡啶合成的底物为 4-氨基-5-苯甲酰基异噁唑-3-甲酰胺和含有反应性 a-亚甲基的选定羰基化合物。反应在催化剂 ZnCl2 或 In(OTf)3 的存在下使用经典方法进行，在无溶剂条件下在微波反应器中使用 ZnCl2 进行。选择的化合物在体外对八种肿瘤细胞系进行测试，以评估其抗增殖活性。
通过 Friedlander 缩合 4-氨基-5-苯甲酰基异噁唑-3-甲酰胺与具有活性亚甲基的选定羰基化合物，得到一系列新型 3,5,6,7-四取代异噁唑并[4,5-b]吡啶衍生物。这些化合物是通过常规和微波方法，在催化剂 ZnCl2 或 In(OTf)3 的存在下获得的。根据元素分析和红外（IR）、核磁共振（1H NMR）和质谱（MS）数据确定产物的结构。选择的化合物在体外对八种肿瘤细胞系进行了抗增殖活性测试。
只有在热浴中使用常规加热，在催化剂 ZnCl2、In(OTF)3 或无溶剂条件下使用微波辐射的情况下，才能获得新型多取代异噁唑并[4,5-b]吡啶衍生物的良好产率。在体外测试的化合物中，只有 6-苯甲酰基-5,7-二苯基异噁唑并[4,5-b]吡啶在 3.9 µg/ml 的浓度下表现出抗增殖活性。
