Synthesis, identification and antiplatelet evaluation of 2-morpholino substituted benzoxazines

A number of 2-morpholino substituted benzoxazines have been prepared in order to test their effectiveness against ADP and collagen induced platelet aggregation. The reaction of 2-thio-1,3-benzoxazines with morpholine has been generalised to enable the use of substituted benzoxazines. Two separate methods were used to prepare 7-O-2-morpholino substituted benzoxazines from 7-hydroxy-2-morpholino benzoxazines. Antiplatelet testing was carried out on 15 of the title compounds. 7-(2-Chloroethoxy)-8-methyl-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one 15d and 7-[2-(4-methylpiperazin-1-yl)ethoxy]-8-methyl-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one 16d showed potent activity against ADP and collagen induced platelet aggregation. The structures of the newly prepared compounds were confirmed by microanalysis as well as the analysis of IR, 1H and 13C NMR.

Graphical abstractA number of novel 2-morpholino substituted benzoxazines were prepared in order to test their effectiveness against ADP and collagen induced platelet aggregation. Compound 16d showed the most potent activity.Figure optionsDownload full-size imageDownload as PowerPoint slide