Uses
Abiraterone, a steroidal cytochrome P 450 17α-hydroxylase-17,20-lyase inhibitor (CYP17), is currently undergoing phase II clinical trials as a potential drug for the treatment of androgen-dependent pr
ostate cancer.
Definition
ChEBI: A 3beta-sterol that is androsta-5,16-dien-3beta-ol substituted at position 17 by a 3-pyridyl group. Administered as the O-acetate, it is used for treatment of metastatic castrate-resistant prostate cance
.
History
Abiraterone (brand name: Zytiga) is an anti-cancer drug developed by Centocor Ortho Biotech Inc. It was first approved by the FDA on 28 April 2011 for the treatment of advanced prostate cancer. In December 2012, the FDA expanded Zytiga's approved use to include treatment of men with advanced (metastatic) castration-resistant prostate cancer prior to chemotherapy. By February 2018, the FDA further approved Zytiga (abiraterone acetate) in combination with prednisone for the treatment of early metastatic prostate cancer.
Manufacturing Process
Diethyl(3-pyridyl)borane (3.38 g, 23 mmol) from Aldrich Chemical Co. Ltd.
was added to a stirred solution of 3β-acetoxyandrosta-5,16-dien-17-yl
trifluoromethanesulphonate (6.94 g, 15 mmol) in THF (75 ml) containing
bis(triphenylphosphine)palladium(II) chloride (0.105 g, 0.15 mmol). An
aqueous solution of sodium carbonate (2 M, 30 ml) was then added and the
mixture heated, with stirring, by an oil bath at 80°C for 1 h, and allowed to
cool. The mixture was partitioned between diethyl ether and water, the ether
phase was dried (Na2CO3), filtered through a short plug of silica, and
concentrated. Chromatography, on elution with light petroleum-diethyl ether
(2:1), afforded the 3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene (4.95 g,
84%) which crystallised from hexane, m.p. 144-145°C.
To a solution of 3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene (4.90 g, 12.5
mmol) in methanol (50 ml) was added an aqueous solution of sodium
hydroxide (10% w/v, 10 ml) and the mixture heated, with stirring, on an oil
bath at 80°C for 5 min, then allowed to cool. The mixture was poured into
water, neutralised with hydrochloric acid (1 M), rebasified with saturated
sodium bicarbonate solution, and extracted with hot toluene. The toluene
extracts were combined, dried (Na2CO3), and concentrated. Chromatography,
on elution with toluene-diethyl ether (2:1) afforded the 17-(3-
pyridyl)androsta-5,16-dien-3β-ol (3.45 g, 79%) which crystallised from
toluene, m.p. 228-229°C.
