Synthesis and antiproliferative activity in vitro of new 3-substituted aminoisoxazolo[5,4-b]pyridines.

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).