Mibolerone

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Mibolerone
Mibolerone structure.png
Mibolerone2.png
Systematic (IUPAC) name
(7α,17β)-17-hydroxy-7,17-dimethylestr-4-en-3-one
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
  • Schedule 3 (US)
Routes of
administration
Oral
Pharmacokinetic data
Metabolism Hepatic
Biological half-life 2-4 hours
Identifiers
CAS Registry Number 3704-09-4 N
ATC code None
PubChem CID: 251636
IUPHAR/BPS 2859
ChemSpider 220460 YesY
UNII 9OGY4BOR8D YesY
KEGG D05025 YesY
ChEBI CHEBI:34849 N
ChEMBL CHEMBL425863 YesY
Synonyms (7R,8R,9S,10R,13S,14S,17S)-17-Hydroxy-7,13,17-trimethyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
Chemical data
Formula C20H30O2
Molecular mass 302.4558 g/mol
 N (what is this?)  (verify)

Mibolerone[pronunciation?] is a potent anabolic steroid which is both higher affinity[1] and more selective[2] for the androgen receptor than metribolone.

Under the brand name "Cheque Drops", Mibolerone was marketed as a veterinary drug by the Upjohn company. It was indicated as an oral treatment for estrous (heat) prevention in adult female dogs.

Synthesis[edit]

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.

Preparation of Mibolerone: BE 610385 ; J. C. Babcock, J. A. Campbell, U.S. Patent 3,341,557 (1962, 1967 both to Upjohn).

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).

References[edit]

  1. ^ 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. PMID 2422638. 
  2. ^ 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. PMID 6333679.