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.
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 μM respectively. Inhibition of DNA-PK activity at concentrations of 1.6-4 μM were tested for 9 products 5i, 7a-e and 9b, 9f and 9j.
Ihmaid
Saleh
S
School of Pharmacy and Applied Science, La Trobe University, P.O. Box 199, Bendigo 3552, Australia. sihmaid@students.latrobe.edu.au
Al-Rawi
Jasim
J
Bradley
Christopher
C
D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D048588:Benzoxazines; D010975:Platelet Aggregation Inhibitors; D051747:DNA-Activated Protein Kinase