Mibolerone 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),[6][7] although potent and significant
progestogenic activity remains present.[8] 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.[9]
Relative affinities (%) of mibolerone and related steroids[10][11]
Values are percentages (%). Reference
ligands (100%) were
progesterone for the
PRTooltip progesterone receptor,
testosterone for the
ARTooltip androgen receptor,
estradiol for the
ERTooltip estrogen receptor,
DEXATooltip dexamethasone for the
GRTooltip glucocorticoid receptor, and
aldosterone for the
MRTooltip mineralocorticoid receptor.
Mibolerone, also known as 7α,17α-dimethyl-19-nortestosterone (DMNT) or as 7α,17α-dimethylestr-4-en-17β-ol-3-one,[8] is a
syntheticestranesteroid and a
17α-alkylatedderivative of
nandrolone (19-nortestosterone). It is the 17α-
methyl derivative of
trestolone (7α-methyl-19-nortestosterone; MENT).[8] Other related AAS include
metribolone (17α-methyl-δ9,11-19-nortestosterone) and
dimethyltrienolone (7α,17α-dimethyl-δ9,11-19-nortestosterone).
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
dienone (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.[12]
Mibolerone is the
generic name of the drug and its
INNTooltip International Nonproprietary Name,
USANTooltip United States Adopted Name, and
BANTooltip British Approved Name.[3][4] It is also known as dimethylnortestosterone (DMNT) and by its former developmental code name U-10997.[3][4]
Brand names
Mibolerone has been marketed under the brand names Cheque Drops and Matenon.[4][3][5]
^Murthy LR, Johnson MP, Rowley DR, Young CY, Scardino PT, Tindall DJ (1986). "Characterization of steroid receptors in human prostate using mibolerone". Prostate. 8 (3): 241–53.
doi:
10.1002/pros.2990080305.
PMID2422638.
S2CID43768386.
^Schilling K, Liao S (1984). "The use of radioactive 7 alpha, 17 alpha-dimethyl-19-nortestosterone (mibolerone) in the assay of androgen receptors". Prostate. 5 (6): 581–8.
doi:
10.1002/pros.2990050603.
PMID6333679.
S2CID86370224.
^
abcMarkiewicz L, Gurpide E (1997). "Estrogenic and progestagenic activities of physiologic and synthetic androgens, as measured by in vitro bioassays". Methods Find Exp Clin Pharmacol. 19 (4): 215–22.
PMID9228646.