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Fluoxymesterone(Halotestin) is a steroid with an androgenic property that is used in primary hypogonadism and testicular failure due to cryptorchidism, vanishing testes syndrome, or orchidectomy; and in hypogonadotrophic hypogonadism and luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary hypothalamic injury from tumors, trauma, or radiation. It mimics the actions of testosterone, which is responsible for normal growth and development of the male sex organs and for the maintenance of secondary sex characteristics. In female postmenopausal patients, fluoxymesterone may be indicated in the palliation of recurrent mammary cancer.

white to light yellow crystal powde

Halotestin, Upjohn, US,1957

Fluoxymesterone is an anabolic steroid with androgenic activity. Fluoxymesterone is used in the treatment of male hypogonadism. Fluoxymesterone showed antitumor effects on pregnancy-dependent mammary tumors TPDMT-4.

stimulates erythropoesis and cell respiration treatment of male hypogonadismdelayed puberty in males, managing metastatic breast cancer in menopausal women

ChEBI: Fluoxymesterone is an anabolic androgenic steroid, a 17beta-hydroxy steroid, an 11beta-hydroxy steroid, a fluorinated steroid and a 3-oxo-Delta(4) steroid. It has a role as an antineoplastic agent and an anabolic agent.

(Fluoxymesterone tablets 10 mg)
Fluoxymesterone promotes growth and development of male reproductive organs, maintains secondary sex characteristics, increases protein anabolism, and decreases protein catabolism. It is used for replacement therapy in conditions associated with symptoms of deficiency or absence of endogenous testosterone; delayed puberty (men); palliation of androgen-responsive recurrent mammary cancer in women who are more than 1 year but less than 5 years postmenopausal (women).

The following description is taken from US Patent 2,793,218.
(a) Preparation of 9/(11)-Dehydro-17-Methyltestosterone: A warm solution of 1 gram of 11α-hydroxy-17-methyltestosterone (US Patent 2,660,586) in 2 ml of dry pyridine was mixed with 1 gram of para-toluenesulfonyl chloride. The mixture was maintained at room temperature for 18 hours and then poured into 25 ml of water. The mixture was stirred until the precipitated oil solidified. The solid was filtered, washed with water and dried to give 1.41 grams of 11α-(p-toluenesulfonyloxy)-17α-methyl-17β-hydroxy-4-androsten-3-one which melted at 144° to 148°C with decomposition and, after crystallization from a mixture of methylene chloride and hexane hydrocarbons, melted at 141° to 144°C with decomposition.
A mixture of 1 gram of the thus-produced 11α-(p-toluenesulfonyloxy)-17αmethyl-17β-hydroxy-4-androsten-3-one, 0.2 gram of sodium formate, 0.57 ml of water and 14 ml of absolute ethanol was heated at its refluxing temperature for 19 hours. The solution was cooled and then poured onto 50 grams of a mixture of ice and water with stirring. The resulting precipitate was filtered and dried to give 0.59 gram of 9(11)-dehydro-17methyltestosterone which melted at 156° to 160°C and, after crystallization from a mixture of methylene chloride and hexane hydrocarbons, melted at 167° to 170°C.
(b) Preparation of 9α-Bromo-11β-Hydroxy-17-Methyltestosterone: To a solution of 1 gram of 9(11)-dehydro-17-methyltestosteronein 50 ml of acetone was added dropwise, with stirring, at 15°C, 1 gram of Nbromoacetamide dissolved in 25 ml of water. A solution of 20 ml of 0.8 N perchloric acid was then slowly added at the same temperature. After 20 minutes, there was added a sufficient amount of a saturated aqueous solution of sodium sulfite to discharge the yellow color of the solution. The resulting mixture was then diluted with 100 ml of water thereby precipitating 1 gram of 9α-bromo-11β-hydroxy-17-methyltestosterone as needles melting at 153° to 155°C.
(c) Preparation of 9,11β-Epoxy-17-Methyltestosterone: A suspension of 1 gram of 9α-bromo-11β-hydroxy-17-methyltestosterone in 30 ml of methanol was titrated with 1 M equivalent of 0.1 N aqueous sodium hydroxide. The resulting mixture was diluted with 50 ml of water and then chilled to about 0°C thereby precipitating 0.64 gram of 9,11β-epoxy-17-methyltestosterone melting at 170° to 176°C which, after crystallization from dilute methanol, melted at 65° to 172°C (with sublimation).
(d) Preparation of 9α-Fluoro-11β-Hydroxy-17-Methyltestosterone: To a solution of 0.5 gram of 9,11β-epoxy-17-methyltestosterone in 10 ml of methylene chloride was added 2 ml of 48% aqueous hydrofluoric acid. The mixture was stirred at room temperature for 5 hours and then cautiously poured with stirring into a mixture of 6 grams of sodium bicarbonate in a mixture of ice and water. The precipitated steroid was extracted with methylene chloride, the extract washed with water and then dried. The solvent was distilled from the dried solution and the residue crystallized from methylene chloride to give 148 mg of 9α-fluoro-11β-hydroxy-17methyltestosterone melting at 265°C with decomposition.

Android (Valeant); Halotestin (Pharmacia & Upjohn); Ora-Testryl (Bristol-Myers Squibb).

Androgen

Fluoxymesterone, 9α-fluoro-11β,17β-dihydroxy-17-methylandrost-4-en-3-one, is ahighly potent, orally active androgen, about 5 to 10 timesmore potent than testosterone. It can be used for all theindications discussed previously, but its great androgenicactivity has made it useful primarily for treatment of theandrogen-deficient male.

Fluoxymesterone is a synthetic androgenic anabolic steroid and is approximately 5 times as potent as natural methyltestosterone. Like testosterone and other androgenic hormones, fluoxymesterone binds to the androgen receptor. It produces retention of nitrogen, sodium, potassium, and phosphorus, increases protein anabolism, decreases amino acid catabolism and decreases urinary excretion of calcium. The antitumour activity of fluoxymesterone appears related to the reduction or competitive inhibition of prolactin receptors or estrogen receptors or production.

By substituting a 9α-fluoro group onto an analog of 17α-methyltestosterone, fluoxymesterone has 20 times the anabolic and 10 times the androgenic activity of 17α-methyltestosterone. It has a mean half-life of 9 hours, and less than 5% of the drug is excreted unchanged. An adverse effect of fluoxymesterone is sodium and water retention that could lead to edema.

Fluoxymesterone is used as an androgen hormonal supplement. An adverse effect of fluoxymesterone is sodium and water retention that could lead to edema. Side effects associated with this agent include closing of the epiphyseal closures, hypercalcemia, and edema. This product should not be given to boys who are in puberty because of its effect on the epiphyseal closures.

Poison by ingestion. Moderatelytoxic by intraperitoneal route. Human systemic effects byingestion: dermatitis, changes in respiratory system andtransaminase activity. Human reproductive effects byingestion: spermatogenesis. An experimental teratogen.

Fluoxymesterone, 9-fluoro-11|?,17|?-dihydroxy-17|á-methylandrost- 4-en-3-one (29.3.8), is made from 11|?-hydroxy-4-androsten-3,17-dione, which is reacted with pyrrolidine to give a dieneamine (29.3.4). This undergoes a reaction with methylmagnesiumiodide, which after hydrolysis forms 11|?,17|?-dihydroxy-17|á-methylandrost- 4-en-3-one (29.3.5). Dehydration of this compound by selective tosylation of the secondary hydroxyl group at C11 using p-toluenesulfonyl chloride and subsequent reaction with a base gives the diene (29.3.6), and the double bond at C9¨CC11 is transformed to an epoxide (29.3.7) by subsequent reaction with N-bromoacetamide in a wet solvent (source of HOBr), and a base. Further reaction with hydrogen fluoride results in an opening of the epoxide ring and the formation of the desired fluoxymesterone (29.3.8).

Fluoxymesterone binds to androgen receptors, suppressing GnRH, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) through a negative feedback mechanism involving the hypothalamus and anterior pituitary. It antagonizes the estrogenic effects in estrogendependent target cells.