Synthesis, structural elucidation and DNA-dependant protein kinase and antiplatelet studies of 2-amino-(5, 6, 7, 8-mono and 7, 8-di-substituted)-1,3-benzoxazines.

摘要

A number of new 2-amino-[5, 6, 7 and 8]-O-substituted 1,3-benzoxazines, and 2-amino 8-methyl-7-O-substituted-1,3-benzoxazines were synthesized. Thirty one new compounds were tested for their effect on collagen induced platelet aggregation and it was found that the most active compounds were 8-methyl-2-morpholin-4-yl-7-(pyridin-3-ylmethoxy)-4H-1,3-benzoxazin-4-one 9f and 8-methyl-2-morpholin-4-yl-7-(pyridin-4-ylmethoxy)-4H-1,3-benzoxazin-4-one 9j with IC(50) = 2 +/- 1.5 and 4 +/- 2 muM respectively. Inhibition of DNA-PK activity at concentrations of 1.6-4 muM were tested for 9 products 5i, 7a-e and 9b, 9f and 9j.