Decadron
Phosphate,MS and D,US,1959
A pro-drug of Dexamethasone (D298800), an anti-inflammatory glucocorticoid. It was found that liposomal DXM-P inhibited both chronic inflammation and joint destruction, whereas free DXM-P failed to prevent joint destruction.
A solution of bis-triethylamine phosphate was prepared by slowly adding 2.36
ml of 85% phosphoric acid to 20 ml of acetonitrile containing 9.9 ml of
triethylamine at 20°C. This solution was added to a stirred solution of 4.70 g
of 9α-fluoro-11β,17α,21-trihydroxy-16α-methyl-1,4-pregnadiene-3,2-dione 21-
methanesulfonate and 20 ml of acetonitrile. The mixture was heated under
reflux for four hours and then evaporated under reduced pressure to a volume
of 12 ml. This mixture was a concentrated solution of 9α-fluoro-11β,17α,21-
trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione 21-phosphate
triethylamine salt with some inorganic phosphate.
The mixture was cooled, 25 ml of methanol added, and the cooled mixture
treated with 33 ml of 1.89 N methanolic sodium methoxide solution. The
precipitated inorganic phosphates were removed by suction filtration and
washed thoroughly with methanol. The combined filtrates were evaporated
under reduced pressure to a volume of 12 ml and treated with 30 ml of
methanol. The resulting cloudy solution was clarified by filtration through
diatomaceous earth. The volume of the filtrate was brought to 40 ml by the
addition of methanol, and 120 ml of ether was added with stirring. The
precipitated product, which was 9α-fluoro-11β,17α,21-trihydroxy-16α-methyl1,4-pregnadiene-3,20-dione 21-phosphate sodium salt, was collected by
suction filtration, and washed with acetone and then with ether. The weight of
the air-dried material was 3.06 g.
