Poreba Krystyna, Wietrzyk Joanna, Opolski Adam
Department of Technology of Drugs, Wroclaw University of Medicine, 1 Nankier Sq., 50-140 Wrocław, Poland.
Acta Pol Pharm. 2003 Jul-Aug;60(4):293-301.
The synthesis of 3-aminoisoxazolo[5,4-b]pyridine [III] and of several new 3-substituted aminoisoxazolo[5,4-b]pyridines is described. 3-Aminoisoxazlo[5,4-b]pyridine [III] was subjected to reactions with the acid halides and substituted aromatic aldehydes, leading to the production of the corresponding amides IV-VII, IX, XI-XVI and new tricyclic pyridoisoxazolopyrimidine VIII and Schiff bases XX-XXIV. 4-Chlorobutyroamide IX cyclized into 3-(pyrrolidinon-1-yl)isoxazolo[5,4-b]pyridine [X]. 3-Chloroacetylaminoisoxaxolo[5,4-b]pyridine [V] in reaction with secondary amines gave 3-aminoacetylaminoisoxazolo[5,4-b]pyridines XVII-XIX. The structures of the products II-XXIV were established on the basis of elemental analysis and spectral data IR, 1H NMR and MS. Selected compounds were tested for their antiproliferative activity in vitro. Two of them: 3-chloroacetyl-[V] and 3-2-bromo-propionylaminoisoxazolo[5,4-b]pyridine [VI] revealed cytotoxic activity against the cells of 8 various human or mouse tumor cell lines applied. Their ID50 (inhibitory dose 50%) values are in the range of the international activity criterion for synthetic agents (4 microg/ml).
描述了3-氨基异恶唑并[5,4 - b]吡啶[III]和几种新的3-取代氨基异恶唑并[5,4 - b]吡啶的合成。3-氨基异恶唑并[5,4 - b]吡啶[III]与酰卤和取代的芳香醛发生反应，生成相应的酰胺IV - VII、IX、XI - XVI以及新的三环吡啶并异恶唑并嘧啶VIII和席夫碱XX - XXIV。4-氯丁酰胺IX环化生成3-(吡咯烷酮-1-基)异恶唑并[5,4 - b]吡啶[X]。3-氯乙酰氨基异恶唑并[5,4 - b]吡啶[V]与仲胺反应生成3-氨基乙酰氨基异恶唑并[5,4 - b]吡啶XVII - XIX。产物II - XXIV的结构通过元素分析以及红外光谱、核磁共振氢谱和质谱等光谱数据确定。对选定的化合物进行了体外抗增殖活性测试。其中两种：3-氯乙酰基-[V]和3-(2-溴丙酰基)氨基异恶唑并[5,4 - b]吡啶[VI]对所应用的8种不同人类或小鼠肿瘤细胞系的细胞显示出细胞毒性活性。它们的ID50（半数抑制剂量）值在合成药物国际活性标准范围内（4微克/毫升）。
