LOMIFYLLINE

Originator

Lomifylline,Yick-Vic Chemicals and

The Uses of LOMIFYLLINE

Lomifylline is a methylxanthine analogue which induces Ca2+-release from intracellular stores via the ryanodine receptor.

Definition

ChEBI: 1,3-dimethyl-7-(5-oxohexyl)purine-2,6-dione is an oxopurine.

Manufacturing Process

A mixture of 560 g of potassium carbonate, 700 ml of ethanol (96%), 404 g of 1,3-dibromopropane and 260 g of ethyl acetoacetate was heated with stirring to go 60°C. After the reaction had subsided, the reaction mixture was refluxed for 5 hours. Then the bulk of the alcohol was distilled off under ordinary pressure and the residue was mixed with 1.5 L of water. The resulting oily layer was separated, and the aqueous phase was extracted with benzene and the benzene layer was combined with the oil. After drying with sodium sulfate the benzene was distilled off and the residue was fractionally distilled 250 g (73% of theory) of 2-methyl-3-carbethoxy-5,6-dihydropyrane of boiling point 105°-108°C were obtained.
140 ml of 63% hydrobromic acid were slowly added at room temperature to 128 g of 2-methyl-3-carbethoxy-5,6-dihydropyrane, and much carbon dioxidewas evolved. After standing for 1 to 2 days at room temperature the mixture was diluted with an equal volume of iced water; the layer of dark colored oil formed was separated, the aqueous phase was extracted with chloroform, and the extract was combined with the oil and washed with a saturated solution of sodium bicarbonate. The solution was dried with sodium sulfate, the chloroform was distilled off under normal pressure, and the residue was fractionally distilled in vacuo. 109 g (81% of theory) of 1-bromohexanone-5 of boiling point 94°-98°C/12 mm Hg were obtained.
A solution of 10.0 g of 1-bromohexanone-5 in 100 ml of ethanol was gradually mixed at the boil with vigorous stirring with 11.3 g of the sodium salt of theophylline in 100 ml of water. After 3 hours refluxing the alcohol was distilled off, and the residual aqueous phase was cooled and made alkaline and extracted with chloroform. The chloroform solution was evaporated and the residue re-crystallized from a little isopropanol to yield 7-(5-oxohexyl) theophylline. MP: 75°-76°C; a yield of about 80% (calculated on the reacted theophylline).

Therapeutic Function

Vasodilator

Metabolism

Not Available