fluazacort

Originator

Azacortid,Richter,Italy,1975

Uses

fluazacort is a glucucorticoid with anti-inflammatory properties used in the treatment of skin diseases.

Definition

ChEBI: Fluazacort is a corticosteroid hormone.

Manufacturing Process

To a solution of 2.4 g of pregna-1,4,9(11)-triene-21-ol-3,20-dione-[17α,16α- d]-2'-methyloxazoline 21-acetate in 24 ml of tetrahydrofuran, 12.8 ml of 0.46 N perchloric acid are added at 15°C under stirring. N-bromoacetamide (1.1 g) is then added to the mixture which is kept far from light, and stirred for 4 hours at room temperature. After lowering the temperature to 10°C, a saturated solution of sodium bisulfite is added in order to decolorize the mixture, which is then poured into 120 ml of ice water. A product separates, which is collected by filtration, washed with water and then dried, thus obtaining 2.81 g of crude 9α-bromo-pregna-1,4-diene-11β,21-diol-3,20-dione- [17α,16α-d]-2'-methyloxazoline-21-acetate (yield 93%), MP 175°C to 176°C. An amount of 2.75 g of 9α-brorno-pregna-1,4-diene-11β,21-diol-3,20-dione- [17α,16α-d]-2'-methyloxazoline-21-acetate is dissolved under nitrogen in 137 ml of a mixture methanol:chloroform (3:2). The solution is put in ice bath and 5.5 ml of 1 N NaOH are then added within 10 minutes followed by 5.5 ml within the next 40 minutes. A strong stirring is provided for 2 hours and the temperature is kept between 0°C and 5°C, then the pH is adjusted to 7 to 8 with glacial acetic acid. The solvent is evaporated in vacuo to 20 ml of volume of solution, that is poured into ice water (130 ml). The product is collected by filtration, washed with water and dried. Yield: 1.6 g (80%), MP 221°C to 222°C. It is pregna-1,4-diene-9β,11β-epoxy-21-ol-3,20-dione-[17α,16α-d]-2'- methyloxazoline.
An amount of 1 g of the above product is dissolved in 9.4 ml of a mixture obtained by mixing 4.67 ml of hydrofluoric acid with 8.5 ml of tetrahydrofuran at the temperature of 0°C. This solution is stirred for 20 hours at the same temperature, then under strong stirring and cooling 20 ml of tetrahydrofuran are added. The solution is subsequently neutralized by the addition of 24 g of sodium bicarbonate followed by 1 g of sodium sulfate. The inorganic substance is collected and washed with ethyl acetate. The filtrate is evaporated to dryness and the product is crystallized from acetone: 0.65 g (yield 61%) of pregna-1,4-dien-9α-fluoro-11β,21-diol-3,20-dione-[17α,16α-d]- 2'-methyloxazoline are obtained, MP 241°C to 244°C [α]D = +83.5 (c. 0.5, CHCl3).The 21-acetate has MP 252°C to 255°C [α]D = +54.8 (c. 0.5, CHCl3).

Therapeutic Function

Antiinflammatory