Mibolerone


Mibolerone, also known as dimethylnortestosterone and sold under the brand names Cheque Drops and Matenon, is a synthetic, orally active, and extremely potent anabolic–androgenic steroid and a 17α-alkylated nandrolone derivative which was marketed by Upjohn for use as a veterinary drug. It was indicated specifically as an oral treatment for prevention of estrus in adult female dogs.

Side effects

Pharmacology

Pharmacodynamics

Mibolerone has both higher affinity and greater selectivity for the androgen receptor than does the related potent AAS metribolone, although potent and significant progestogenic activity remains present. However, another study found that mibolerone and metribolone had similar affinity for the progesterone receptor but that mibolerone only had around half the affinity of metribolone for the AR.

Chemistry

Mibolerone, also known as 7α,17α-dimethyl-19-nortestosterone or as 7α,17α-dimethylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a 17α-alkylated derivative of nandrolone. It is the 17α-methyl derivative of trestolone. Other related AAS include metribolone and dimethyltrienolone.

Synthesis

The original patented synthesis was revised: Precursor :
The reaction of Bolandione with triethyl orthoformate gave 3-Ethoxyestra-3,5-dien-17-one in 64% yield. Organometallic reaction with methyl lithium followed by hydrolysis of the dienol ether gave Normethandrone in 40% yield. In an alternative synthesis, reaction of Estr-5-ene-3,17-dione with methanol catalyzed by malonic acid gave a near quantitivate yield of the ketal, 3,3-dimethoxyestr-5-en-17-one . Reaction with the organometallic reagent and hydrolysis in this case afforded a much higher yield of product than in the first case. Oxidation with chloranil afforded a 75.6% yield of 17-methyl-6-dehydronandrolone. Conjugate addition of methyl lithium in the presence of cuprous iodide gave a 72.5% yield of mibolerone.
In the other synthesis heating nandrolone acetate with chloranil gives 6-Dehydronandrolone Acetate , and reaction of that compound with methylmagnesium bromide in the presence of cuprous chloride gives, Trestolone . The alcohol at C17 is then oxidized to a ketone, Mentabolan . Enamines are commonly used to activate adjacent functions; they are also not infrequently used, as in this case, as protecting groups. Thus, reaction of the intermediate with pyrrolidine gives dienamine PC135056261. This transformation emphasizes the clear difference in reactivity between ketones at C7 and C17. A second methyl Grignard addition gives the corresponding 17α-methyl derivative. Hydrolysis of the enamine function then affords mibolerone.
For SAR purposes compare for bolasterone and calusterone.

History

Mibolerone was first synthesized in 1963.

Society and culture

Generic names

Mibolerone is the generic name of the drug and its,, and. It is also known as dimethylnortestosterone and by its former developmental code name U-10997.

Brand names

Mibolerone has been marketed under the brand names Cheque Drops and Matenon.