Mibolerone has both higheraffinity and greaterselectivity for theandrogen receptor (AR) than does the related potent AASmetribolone (17α-methyl-19-nor-δ9,11-testosterone),[6][7] although potent and significantprogestogenic activity remains present.[8] However, another study found that mibolerone and metribolone had similar affinity for theprogesterone 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 (%). Referenceligands (100%) wereprogesterone for thePRTooltip progesterone receptor,testosterone for theARTooltip androgen receptor,estradiol for theERTooltip estrogen receptor,DEXATooltip dexamethasone for theGRTooltip glucocorticoid receptor, andaldosterone for theMRTooltip 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 asyntheticestranesteroid and a17α-alkylatedderivative ofnandrolone (19-nortestosterone). It is the 17α-methyl derivative oftrestolone (7α-methyl-19-nortestosterone; MENT).[8] Other related AAS includemetribolone (17α-methyl-δ9,11-19-nortestosterone) anddimethyltrienolone (7α,17α-dimethyl-δ9,11-19-nortestosterone).
Nandrolone (1) appears to be used to make mibolerone. For comparison, also seebolasterone andcalusterone. The first step involves extending the conjugation of the enone function by an additional double bond.Chloranil (tetrachloroquinone) is the forerunner ofdichlorodicyanoquinone (DDQ), a reagent used extensively for introducing additional unsaturation in theprogestin andcorticoid series.
In the case at hand, heating acetate (1) withchloranil gives the conjugateddienone (2), and reaction of that compound withmethylmagnesium bromide in the presence ofcuprous chloride leads to addition of the methyl group to position 7 at the end of the conjugated system (3). Thestereochemistry 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, asprotecting groups. Thus, reaction of the intermediate withpyrrolidine givesdienamine (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 theenamine function then affords mibolerone (6).
The same structure of3 and4 also containing an 11β-fluoro group has also been described in the patent literature.[12]
Mibolerone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name, andBANTooltip British Approved Name.[3][4] It is also known asdimethylnortestosterone (DMNT) and by its former developmental code nameU-10997.[3][4]
^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.
