NORETHYNODREL

Chemical properties

White to Off-White Solid

Originator

Enovid, Searle ,US,1957

The Uses of NORETHYNODREL

Norethynodrel (Norethindrone EP Impurity D) (>90%) is a progestin used in Enovid, an oral contraceptive, also used in the treatment of endometriosis and hypermenorrhea.

The Uses of NORETHYNODREL

Norethynodrel is a progestin used in Enovid, an oral contraceptive, also used in the treatment of endometriosis and hypermenorrhea.

Background

A synthetic progestational hormone with actions and uses similar to those of PROGESTERONE. It has been used in the treatment of functional uterine bleeding and endometriosis. As a contraceptive, it has usually been administered in combination with MESTRANOL.

Definition

ChEBI: Norethynodrel is an oxo steroid.

Manufacturing Process

Convenient starting materials are the ethers of 3-hydroxy-13-methyl1,4,6,7,8,9,11,12,13,14,16,17-dodecahydro-15H-cyclopenta-α-phenanthren 2474 17-one described in US Patent 2,655,518, according to US Patent 2,691,028 where the following preparation is also described. The methyl ether is also designated as 3-methoxy-17-oxo-2,5-estradiene
A stirred solution of 10.6 parts of 3-methoxy-13-methyl-1,4,6,7,8,9,11,12,13, 14,16,17dodecahydro-15H-cyclopenta-α-phenanthren-17-one in 700 parts of anhydrous ether and 45 parts of dry toluene is cooled to 0°C and saturated with dry acetylene. While a slow stream of acetylene is passed through the reaction mixture, a solution of 20 parts of potassium t-amylate in 135 parts of anhydrous t-pentanol is added in the course of 15 minutes with stirring. Passage of acetylene and stirring are continued for an additional 4? hours. After standing at 0°C for 16 hours, the mixture is washed with aqueous ammonium chloride solution until the aqueous phase is neutral, then with water and saturated sodium chloride solution. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to a residue of about 250 parts. 500 parts of petroleum ether are added and after standing at 0°C for an hour, the mixture is filtered. The collected precipitate is recrystallized from ether. The resulting 3-methoxy-13-methyl-17-ethynyl1,4,6,7,8,9,11,12,13,14,16,17-dodecahydro-15H-cyclopenta-α-phenanthren17-ol melts at about 181° to 182°C.
To a refluxing solution of 10 parts of 3-methoxy-17-ethynyl-17-hydroxy-13methyl-1,4,6,7,8,9,11,12,13,14,16,17-dodecahydro-15H-cyclopenta-αphenanthrene in 500 parts of methanol, 20 parts of glacial acetic acid are added. Refluxing is continued for 7 minutes, water is added to the point of turbidity and the reaction mixture is permitted to come to room temperature. The precipitate is collected on a filter and recrystallized from aqueous methanol. The 13-methyl-17-ethynyl-17-hydroxy-1,2,3,4,6,7,8,9,11,12,13,14, 16,17-tetradecahydro-15H-cyclopenta-α-phenanthren-3-one thus obtained melts at about 169° to 170°C.

Therapeutic Function

Progestin

Safety Profile

Suspected carcinogen with experimental tumorigenic data. Human and experimental reproductive effects. Mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

Metabolism

Not Available