Routes of
administration Oral Metabolism Molar mass 302.4558 g/mol | ATC code none Biological half-life 2–4 hours Route Oral administration | |
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AHFS/Drugs.com International Drug Names Legal status CA: Schedule IV
US: Schedule III | ||
Mibolerone (INN, USAN, BAN) (brand names Cheque Drops, Matenon; developmental code name U-10997), also known as 7α,17α-dimethyl-19-nortestosterone (DMNT), is a potent, orally active anabolic-androgenic steroid (AAS) and 17α-alkylated derivative of nandrolone (19-nortestosterone) that was marketed by Upjohn for use as a veterinary drug. It was indicated as an oral treatment for prevention of estrus (heat) in adult female dogs. Mibolerone is the 17α-methyl derivative of trestolone (7α-methyl-19-nortestosterone; MENT). It has both higher affinity and greater selectivity for the androgen receptor (AR) than does the related potent AAS metribolone (17α-methyl-19-nor-δ9,11-testosterone), although potent and significant progestogenic activity remains present. However, another study found that mibolerone and metribolone had similar affinity for the progesterone receptor (PR) but that mibolerone only had around half the affinity of metribolone for the AR.
Synthesis
Nandrolone (1) appears to be used to make mibolerone. For comparison, also see bolasterone and calusterone. The first step involves extending the conjugation of the enone function by an additional double bond. Chloranil (tetrachloroquinone) is the forerunner of dichlorodicyanoquinone (DDQ), a reagent used extensively for introducing additional unsaturation in the progestin and corticoid series.
In the case at hand, heating acetate (1) with chloranil gives the conjugated dieneone (2), and reaction of that compound with methylmagnesium bromide in the presence of cuprous chloride leads to addition of the methyl group to position 7 at the end of the conjugated system (3). The stereochemistry of the product again illustrates the preference for additions from the backside. The alcohol at C17 is then oxidized to a ketone (4). 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 (5). 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 (6).
The same structure of 3 and 4 also containing an 11β-fluoro group has also been described in the patent literature.