Zinterol hydrochloride

Originator

Zinterol Hydrochloride,ZYF Pharm Chemical

The Uses of Zinterol hydrochloride

Zinterol Hydrochloride is an acidic salt of Zinterol (Z460000). Zinterol is a β2-adrenergic agonist. It can be used to induce smooth muscle relaxation in the lungs, gastrointestinal tract, uterus, and various blood vessels.

The Uses of Zinterol hydrochloride

Bronchodilator.

Manufacturing Process

A). 2'-Hydroxy-5'-([N-(2-methyl-1-phenyl-2-propyl)glycyl]methane- sulfonanilide hydrobromide:
To a solution of α,α-dimethylphenthylamine (120 g, 0.8 mole) in 1.1 liter of acetonitrile is added 5'-bromoacetyl-2'-hydroxymethanesulfonanilide (108 g, 0.35 mole) in a period of 5 minutes. The resulting solution is refluxed for 5 minutes on a steam bath and then permitted to stand for 25 minutes at room temperature after which it is chilled and acidified with 5 N ethanolic hydrogen bromide. The acidified mixture is concentrated in vacuum until a thick slurry is obtained. After standing overnight at room temperature, the slurry is filtered and the crude product triturated with 2-butanone, filtered, washed with 2- butanone and dried to 86.3 g, (54%), MP: 217.5-221°C (dec.).
B). 2'-Hydroxy-5'-(1-hydroxy-2-(2-methyl-1-phenyl-2-propylamino)ethyl) methanesulfonanilide hydrobromide:
2'-Hydroxy-5'-([N-(2-methyl-1-phenyl-2-propyl)glycyl]methanesulfonanilide hydrobromide (132 g, 0.29 mole is dissolved in 2 liters of hot methanol, the methanolic solution is allowed to cool to room temperature and 13 g 10% palladium on carbon catalyst suspended in 50 ml of water is added. Hydrogenation of the stirred mixture is carried out under 1-3 atm. of pressure for 17 hours during which time 0.31 mole of hydrogen is absorbed. The catalyst is filtered and the filtrate concentrated under reduced pressure until a thick slurry is obtained. Isoptopanpl is added tothed slurry and the mixture is again concentrated in vacuum to remove water by azeotropic distillation. Trituration of residual solid with 2-propanol and collection on a filter affords 100.5 g (76% yield) of desired product, MP: 194.5-195.5°C (dec.).
2'-Hydroxy-5'-(1-hydroxy-2-(2-methyl-1-phenyl-2-propylamino)ethyl) methanesulfonanilide base:
2'-Hydroxy-5'-(1-hydroxy-2-(2-methyl-1-phenyl-2-propylamino)ethyl)
methanesulfonanilide hydrobromide (47.7 g) is refluxed with 100 ml of methanol. The material only partly dissolves. A solution of 6.5 g of potassium hydroxide in 25 ml of methanol is then added to the suspension followed by 1 L of water. The mixture is thoroughly stirred and cooled to 5-10°C. The precipitate is collected on a filter and washed with water until a negative test for bromide using silver nitrate is obtained. The product is dried in an oven at 65°C, yield 36 g.

Therapeutic Function

Bronchodilator

Storage

Store at +4°C