Zanoterone

Originator

Zanoterone ,Sterling Drug (Sanofi-Aventis)

The Uses of Zanoterone

Anti-androgen.

Definition

ChEBI: Zanoterone is a steroid. It derives from a hydride of an estrane.

Manufacturing Process

1). A solution of methanesulfonylhydrazide (0.0303 mole) in tetrahydrofuran (70 ml, 30 ml for rinsing) was added with stirring to a solution of (2α,5α,17α)-2-(diethoxymethyl)-17-[(trifluororacetyl)oxy]pregn-20-yn-3-one (0.025 mole) in tetrahydrofuran (190 ml). The mixture was allowed to stand for 3 days at room temperature, heated under reflux for 4 h and evaporated. The residue was purified by crystallization and recrystallization from methanol, affording (5α,17α)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2-c]pyrazol-17-ol trifluoroacetate (ester), 69% yield, MP: 166°-168°C.
The above ester (10.24 g, 0.0200 mole) in 100 ml of a solution prepared from chloroform (210 ml), ethanol (100 ml) and concentrated aqueous ammonia (10 ml) was allowed to stand at room temperature for 2 h, diluted with chloroform (250 ml), and washed with dilute hydrochloric acid (2 N, 250 ml). The chloroform layer was dried and removed of chloroform under vacuum. A solution of the residue in dichloromethane (95 ml) and ether (5 ml) was passed through silica gel (50 g) using more dichloromethane-ether (19:1, 600 ml). Evaporation of the solvent and recrystallization of the residue from acetonitrile afforded (5α,17α)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2- c]pyrazol-17-ol (7.07 g, 85% yield, MP: 202°-203°C). It may be also made another way.
2). A solution of methanesulfonylhydrazide (82.5 g, 0.75 mole) in acetic acid (100 ml) was added with stirring over 5 min to a mixture of (5α,17α)-2- (acetoxymethylene)-17-hydroxypregn-20-yn-3-one (197 g, 0.51 mole) and acetic acid (1 L). The mixture was stirred for 1 h at room temperature, forming a deep yellow solution, which was poured with vigorous stirring into ice-water (6 L). The resulting solid was collected by filtration, washed twice with water (500 ml each time), pressed dry, washed twice again with water (500 ml each time), dried (245 g), recrystallized, first from acetonitrile (2.5 volumes) and then from methanol (6.6 volumes), dried, ground, and redried, affording (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol (137.8 g, 65% yield, MP: 194°-196°C).

Therapeutic Function

Antiandrogen